TABLE OF CONTENT
1. Thyroid Gland.• Introduction.• Hormones of Thyroid Gland.• Diseases of Thyroid Gland.
2. Adrenal Gland.• Introduction.• Parts of Adrenal Gland.• Hormones of Adrenal Gland.• Diseases of Adrenal Gland.• Functions of Adrenal Gland.• Conclusion.
3. Gonads.• Testis.• Ovary.• Hormones.
•The thyroid is a small gland, measuring about 2 inches (5 centimeters) across, that lies just under the skin below the Adam's apple in the neck.
•The two halves (lobes) of the gland are connected in the middle (called the isthmus), giving the thyroid gland the shape of a bow tie.
•Normally, the thyroid gland cannot be seen and can barely be felt.
• If it becomes enlarged (goiter), doctors can feel it easily, and a prominent bulge may appear below or to the sides of the Adam's apple.
•The thyroid gland secretes thyroid hormones, which control the speed at which the body's chemical functions proceed (metabolic rate).
•Thyroid hormones influence the metabolic rate in two ways: by stimulating almost every tissue in the body to produce proteins and by increasing the amount of oxygen that cells use.
•Thyroid hormones affect many vital body functions: the heart rate, the respiratory rate, the rate at which calories are burned, skin maintenance, growth, heat production, fertility, and digestion.
•The two thyroid hormones are T4 (thyroxine) and T3 ( triiodothyronine).T4, the major hormone produced by the thyroid gland, has only a slight, if any, effect on speeding up the body's metabolic rate. Instead, T4 is converted into T3, the more active hormone
•.The conversion of T4 to T3 occurs in the liver and other tissues.
• Many factors control the conversion of T4 to T3, including the body's needs from moment to moment and the presence or absence of illnesses.
•Most of the T4 and T3 in the bloodstream is carried bound to a protein called thyroxine-binding globulin.
• Only a little of the T4 and T3 are circulating free in the blood. However, it is this free hormone that is active. When the free hormone is used by the body, some of the bound hormone is released from the binding protein.
HORMONES OF THYROID GLAND:
The Thyroid gland secretes 3 types of hormones. They are:
• Thyroxine (Tetra-iodothyronine,T4)
Thyroxine, or 3,5,3',5'-tetraiodothyronine (often abbreviated as T4), a form of thyroid hormons is the major hormone secreted by the follicular cells of the thyroid gland. Thyroxine is synthesized via the iodination and covalent bonding of the phenyl portions of tyrosine residues found in an initial peptide, thyroglobulin, which is secreted into thyroid granules. These iodinated diphenyl compounds are cleaved from their peptide backbone upon being stimulated by thyroid-stimulating hormone. More in the T3 and T4 section of thyroid.
T4 is transported in blood, with 99.95% of the secreted T4 being protein-bound, principally to thyroxine-binding globulin (TBG), and, to a lesser extent, to transthyretin and serum albumin. T4 is involved in controlling the rate of metabolic processes in the body and influencing physical development.Administration of thyroxine has been shown to significantly increase the concentration of nerve growth factor in the brains of adult mice.Thyroxine is a prohormone and a reservoir for the active thyroid hormone triiodothyronine (T3), which is about four times more potent. T4 is converted in the tissues by deiodinases, including thyroid hormone iodine peroxidase (TPO), to T3. The "D" isomer is called "Dextrothyroxine"and is used as a lipid modifying agent. The half-life of thyroxine once released into the blood circulatory system is about 1 week.The hormone was synthesised in 1927 by British chemists Charles Robert Harington and George Barger.
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.
Production of T3
T3 is metabolically active hormone that is produced from T4. T4 is deiodinated by two deiodinase enzymes to produce the more-active triiodothyronine:1. Type I present within the liver and accounts for 80% of the deiodination of T4
2. Type II present within the pituitary gland.T4 is synthesised in the thyroid gland follicular cells as follows.
1. The Na+/I- symporter transports two sodium ions across the basement membrane of the follicular cells along with an iodine ion. This is a secondary active transporter that utilises the concentration gradient of Na+ to move I- against its concentration gradient.2. I- is moved across the apical membranae into the colloid of the follicle.
3. Thyroperoxidase oxidises two I- to form I2. Iodide is non-reactive, and only the more reactive iodine is required for the next step.4. The thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid. The thyroglobulin was synthesised in the ER of the follicular cell and secreted into the colloid.5. Thyroid-stimulating hormone (TSH) released from the pituitary gland binds the TSH receptor ( a Gs protein-coupled receptor) on the basolateral membrane of the cell and stimulates the endocytosis of the colloid.
IUPAC name(2S)-2-amino-3- [4-(4-hydroxy-3-iodo-phenoxy)-
6. The endocytosed vesicles fuse with the lysosomes of the follicular cell. The lysosomal enzymes cleave the T4 from the iodinated thyroglobulin.7. These vesicles are then exocytosed, releasing the thyroid hormones.In the follicular lumen, tyrosine residues become iodinated. This reaction requires hydrogen peroxide. Iodine bonds carbon 3 or carbon 5 of tyrosine residues of thyroglobulin in a process called organification of iodine. The iodination of specific tyrosines yields monoiodotyrosine (MIT) and diiodotyrosine (DIT). One MIT and one DIT are enzymatically coupled to form T3. The enzyme is thyroid peroxidase.
Mechanism of actionThe T3 (and T4) bind to nuclear receptors, thyroid receptors. T3 (and T4) are very lipophilic and able to pass through the phospholipid bilayers of target cells. The lipophilicity of T3 (and T4) requires their binding to the protein carrier thyroid-binding protein (TBG) for transport in the blood. The thyroid receptors bind to response elements in gene promoters, thus enabling them to activate or inhibit transcription. The sensitivity of a tissue to T3 is modulated through the thyroid receptors.
Effects of T3
T3 increases the basal metabolic rate and, thus, increases the body's oxygen and energy consumption. The basal metabolic rate is the minimal caloric requirement needed to sustain life in a resting individual. T3 acts on the majority of tissues within the body, with a few exceptions including the spleen and testis. It increases the production of the Na+/K+ -ATPase and, in general, increases the turnover of different endogenous macromolecules by increasing their synthesis and degradation.ProteinT3 stimulates the production of RNA Polymerase I and II and, therefore, increases the rate of protein synthesis. It also increases the rate of protein degradation, and, in excess, the rate of protein degradation exceeds the rate of protein synthesis. In such situations, the body may go into negative ion balance.
GlucoseT3 potentiates the effects of the β-adrenergic receptors on the metabolism of glucose. Therefore, it increases the rate of glycogen breakdown and glucose synthesis in gluconeogenesis. It also potentiates the effects of insulin, which have opposing effects.LipidsT3 stimulates the breakdown of cholesterol and increases the number of LDL receptors, therefore increasing the rate of lipolysis.T3 also affects the cardiovascular system. It increases the cardiac output by increasing the heart rate and force of contraction. This results in increased systolic blood pressure and decreased diastolic blood pressure. The latter two effects act to produce the typical bounding pulse seen in hyperthyroidism.T3 also has profound effect upon the developing embryo and infants. It affects the lungs and influences the postnatal growth of the central nervous system. It stimulates the production of myelin, neurotransmitters, and axon growth. It is also important in the linear growth of bones.NeurotransmittersT3 may increase serotonin in the brain, particularly in the cerebral cortex, and down-regulate 5HT-2 receptors, based on studies in which T3 reversed learned helplessness in rats and physiological studies of the rat brain
Calcitonin is a 32-amino acid linear polypeptide hormone that is produced in humans primarily by the parafollicular cells (also known as C-cells) of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).It has been found in fish, reptiles, birds, and mammals. Its importance in humans has not been as well established as its importance in other animals, as its function is usually not significant in the regulation of normal calcium homeostasis
BiosynthesisCalcitonin is formed by the proteolytic cleavage of a larger prepropeptide, which is the product of the CALC1 gene (CALCA). The CALC1 gene belongs to a superfamily of related protein hormone precursors including islet amyloid precursor protein, calcitonin gene-relate peptide, and the precursor of adrenomedullin
Calcitonin/calcitonin-related polypeptide, alpha
NMR solution structure of salmon calcitonin in SDS micelles
PhysiologyThe hormone participates in calcium (Ca2+) and phosphorus metabolism. In many ways, calcitonin counteracts parathyroid hormone (PTH).More specific, calcitonin affects blood Ca2+ levels in four ways:
Inhibits Ca2+ absorption by the intestinesInhibits osteoclast activity in bonesInhibits phosphate reabsorption by the kidney tubulesCalcitonin inhibits tubular reabsorption of Ca2+, leading to increased rates of its loss
in urine.Secretion of calcitonin is stimulated by:
an increase in serum [Ca2+]gastrin and pentagastrin.
ActionsIts actions, in a broad sense, are:Bone mineral metabolism:
Protect against calcium loss from skeleton during periods of calcium mobilization, such as pregnancy and, especially, lactation
Serum calcium level regulationPrevent postprandial hypercalcemia resulting from absorption of Ca2+ from foods
during a mealVitamin D regulation
A satiety hormone:Inhibit food intake in rats and monkeys - May have CNS action involving the
regulation of feeding and appetite
DISEASES OF THYROID GLAND:
• Hashimoto's thyroiditis.
• Exophthalmic goitre.
Hypothyroidism is a deficiency of thyroid hormone in humans and other vertebrates.
It can be due to an abnormality in the thyroid gland, or less commonly, the pituitary gland or hypothalamus.
It can result from a lack of a thyroid gland due to iodine-131, used to treat thyroid cancer and hyperthyroidism, its surgical removal, or its absence at birth.
Cretinism is a form of hypothyroidism found in infants.
Signs and symptomsIn adults, hypothyroidism is associated with the following symptoms:
CHILD SUFFERING FROM HYPOTHYROIDISM
•EarlyPoor muscle tone (muscle hypotonia)FatigueCold intolerance, increased sensitivity to coldConstipationDepressionMuscle cramps and joint painGoiterThin, brittle fingernailsCoarse hairPalenessDecreased sweatingDry, itchy skin
Weight gain and water retentionBradycardia (low heart rate – fewer than sixty beats per minute)•Late
Slow speech and a hoarse, breaking voice deepening of the voice can also be noticed, caused by Reinke's
Edema.Dry puffy skin, especially on the faceThinning of the outer third of the eyebrows (sign of Hertoghe)Abnormal menstrual cyclesLow basal body temperature
About three percent of the general population is hypothyroid.
Factors such as iodine deficiency or exposure to iodine-131 from nuclear fallout, which is absorbed by the thyroid gland like regular iodide and destroys its cells, can increase that risk. There are a number of causes for hypothyroidism.
Iodine deficiency is the most common cause of hypothyroidism worldwide.In iodine-replete individuals hypothyroidism is generally caused by Hashimoto's thyroiditis, or otherwise as a result of either an absent thyroid gland or a deficiency in stimulating hormones from the hypothalamus or pituitary.
Hypothyroidism can result from postpartum thyroiditis, a condition that affects about 5% of all women within a year of giving birth.
The first phase is typically hyperthyroidism; the thyroid then either returns to normal, or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring life-long treatment.
Hypothyroidism can also result from sporadic inheritance, sometimes autosomal recessive.
Hypothyroidism is also a relatively common disease in domestic dogs, with some specific breeds having a definite predisposition
TreatmentHypothyroidism is treated with the levorotatory forms of thyroxine (levothyroxine) (L-T4) and triiodothyronine (liothyronine) (L-T3).
Both synthetic and animal-derived thyroid tablets are available and can be prescribed for patients in need of additional thyroid hormone.
Thyroid hormone is taken daily, and doctors can monitor blood levels to help assure proper dosing. There are several different treatment protocols in thyroid replacement therapy:
T4 only This treatment involves supplementation of levothyroxine alone, in a synthetic form. It is currently the standard treatment in mainstream medicine.
T4 and T3 in combination-This treatment protocol involves administering both synthetic L-T4 and L-T3 simultaneously in combination.Desiccated thyroid extract Desiccated thyroid extract is an animal based thyroid extract, most commonly from a porcine source.
It is also a combination therapy, containing natural forms of L-T4 and L-T3.
Myxedema (British English: myxoedema) describes a specific form of cutaneous and dermal edema secondary to increased deposition of connectiv tissue components (like glycosaminoglycans,hyaluronic acid, and other mucopolysaccharides) in subcutaneous tissue as seen in various forms of hypothyroidism and Graves' disease.
Cause•The increased deposition of glycosaminoglycan is not fully understood, however two mechanisms predominate.
CHILD SUFFERING FROM MYXODEMA.
•Exophthalmos in particular results from TSH receptor stimulation on fibroblasts behind the eyes which leads to increased glycosaminoglycan deposition.
• It is thought that many cells responsible for forming connective tissue react to increases in TSH levels.
•Secondarily, in autoimmune thyroid diseases lymphocytes react to the TSH receptor.
•Thus, in addition to the inflammation within the thyroid any cell that expresses the TSH receptor will likely experience lymphocytic infiltrates as well.
•The inflammation can cause tissue damage and scar tissue formation explaining the deposition of glycosaminoglycans.
•The increased deposition of glycosaminoglycans causes an osmotic edema and fluid collection.
•Hashimoto's thyroiditis is the most common cause of myxedema in the United States.
It was first described by the Japanese specialist Dr. Hashimoto Hakaru in Germany in 1912.
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune processes.
It was the first disease to be recognised as an autoimmune disease.
Signs and symptomsHashimoto's thyroiditis very often results in hypothyroidism with bouts of:
Hashimoto's when presenting as mania is known as Prasad's syndrome after Ashok Prasad, the psychiatrist who first described it
Physiologically, antibodies against thyroid peroxidase and/or thyroglobulin cause gradual destruction of follicles in the thyroid gland. Accordingly, the disease can be detected clinically by looking for these antibodies in the blood. It is also characterized by invasion of the thyroid tissue by leukocytes, mainly T-lymphocytes. It is associated with non-Hodgkin lymphoma.
Symptoms of Hashimoto's thyroiditis include weight gain, depression, mania, sensitivity to heat and cold , paresthesia, fatigue, panic attacks, bradycardia, tachycardia, high cholesterol, reactive hypoglycemia, constipation, migraines, muscle weakness, cramps, memory loss, infertility and hair loss.
Hashimoto's thyroiditis is often misdiagnosed as depression, cyclothymia, PMS, and, less frequently, as bipolar disorder or as an anxiety disorder. Testing for thyroid-stimulating hormone (TSH) and anti-thyroid antibodies can resolve any diagnostic difficulty.
Hypothyroidism caused by Hashimoto's Thyroiditis is treated with thyroid hormone replacement agents such as levothyroxine or desiccated thyroid extract.
A tablet taken once a day generally keeps the thyroid hormone levels normal.
In most cases, the treatment needs to be taken for the rest of the patient's life. In the event that hypothyroidism is caused by Hashimoto's Thyroiditis, it is recommended that the TSH levels be kept under 3.0.
As long as the patient's thyroid is active, the body will continue to attack it ,and this can wreak havoc on the patient's TSH levels and symptoms.
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones (a serious metabolic imbalance known as hyperthyroidism and thyrotoxicosis).
This is caused by autoantibodies to the TSH-receptor (TSHR-Ab) that activate that TSH-receptor (TSHR), thereby stimulating thyroid hormone synthesis and secretion, and thyroid growth (causing a diffusely enlarged goiter).
The resulting state of hyperthyroidism can cause a dramatic constellation of neuropsychological and physical signs and symptoms, which can severely compromise the patients’ ability to maintain jobs and relationships
LADY SUFFERING FROM GRAVE’S DISEASE
Due to Graves' ophthalmopathyGraves' ophthalmopathy is characterized by inflammation of the extraocular muscles, orbital fat and connective tissue. It results in the following symptoms, which can be extremely distressing to the patient:Most frequent are symptoms due toconjunctival or corneal irritation: burning, photophobia, tearing, pain, and a gritty or sandy sensation.Protruding eyeballs (known as proptosis and exophthalmos)Diplopia (double vision) is common.Limitation of eye movement (due to impairment of eye muscle function).Periorbital and conjunctival edema (accumulation of fluid beneath the skin around the eyes).Infiltrative dermopathy (pretibial myxedema).In severe cases, the optic nerve may be compressed and acuity of vision impaired.Occasionally loss of vision.
TreatmentIt is yet unknown how to interrupt the autoimmune processes of Graves' disease, which means treatment has to be indirect. The link that is targeted is the thyroid gland, via three different methods (which have not changed fundamentally since the introduction of antithyroid drugs and radioactive iodine in the 1940s). These are the use of antithyroid drugs (which reduce the production of thyroid hormone), partial or complete destruction of the thyroid gland by ingestion of radioactive iodine (radioiodine) and partial or complete surgical removal of the thyroid gland (thyroidectomy)
•The body has two adrenal glands, one near the top of each kidney. •The inner part (medulla) of the adrenal glands secretes hormones, such as adrenaline (epinephrine), that help control blood pressure, heart rate, sweating, and other activities also regulated by the sympathetic nervous system.
•The outer part (cortex) secretes different hormones, including corticosteroids (cortisone-like hormones, such as cortisol) and mineralocorticoids (particularly aldosterone, which controls blood pressure and the levels of salt and potassium in the body).
•The adrenal glands also play a role in stimulating the production of androgens (testosterone and similar hormones).
A Close Look at the Adrenal Glands:•The adrenal glands are controlled in part by the brain. •The hypothalamus, a small area of the brain involved in hormonal regulation, produces corticotropin-releasing hormone and antidiuretic hormone. •These two hormones trigger the pituitary gland to secrete corticotropin (also known as adrenocorticotropic hormone or ACTH), which stimulates the adrenal glands to produce corticosteroids. •The renin-angiotensin-aldosterone system, regulated mostly by the kidneys, causes the adrenal glands to produce more or less aldosterone.•The body controls the levels of corticosteroids according to need. •The levels tend to be much higher in the early morning than later in the day. When the body is stressed, from illness or otherwise, the levels of corticosteroids increase dramatically.
Parts of Adrenal Gland:
•Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively.
•It is also a secondary site of androgen synthesis.
Layers of cortex.
Layer Name Primary product
Most superficial cortical layer zona glomerulosa mineralocorticoids
Middle cortical layer zona fasciculata glucocorticoids (e.g., cortisol)
Deepest cortical layer zona reticularis
weak androgens (e.g., dehydroepiandrosterone, adrenosterone)
Notably, the reticularis in all animals is not always easily distinguishable and dedicated to androgen synthesis. In rodents, for instance, the reticularis also generates corticosteroids (specifically corticosterone, not cortisol). The two layers are collectively referred to as the fasciculo-reticularis. Female rodents also exhibit another cortical layer called the "X zone" whose function is not yet clear.
•All adrenocortical hormones are synthesized from cholesterol. Cholesterol is transported into the adrenal gland. The steps up to this point occur in many steroid-producing tissues. Subsequent steps to generate aldosterone and cortisol, however, primarily occur in the adrenal cortex:
Progesterone → (hydroxylation at C21) → 11-Deoxycorticosterone → (two further hydroxylations at C11 and C18) → Aldosterone
Progesterone → (hydroxylation at C17) → 17-alpha-hydroxyprogesterone → (hydroxylation at C21) → 11-Deoxycortisol → (hydroxylation at C11) → Cortisol
Production of HormonesThe adrenal cortex produces a number of different corticosteroid hormones.
•They are produced in the zona glomerulosa.
•The primary mineralocorticoid is aldosterone. Its secretion is regulated by the oligopeptide angiotensin II (angiotensin II is regulated by angiotensin I, which in turn is regulated by renin).
•Aldosterone is secreted in response to high extracellular potassium levels, low extracellular sodium levels, and low fluid levels and blood volume.
•Aldosterone affects metabolism in different ways:It increases urinary excretion of potassium ions.It increases interstitial levels of sodium ions.It increases water retention and blood volume.
Mode of action
The effects of mineralocorticoids are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and signaling cascades.
Genomic mechanisms•Mineralocorticoids bind to the cytosolic mineralocorticoid receptor. This type of receptor gets activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly formed receptor-ligand complex tests itself into the cell nucleus, where it binds to many hormone response elements (HRE) in the promoter region of the target genes in the DNA.
•The opposite mechanism is called transrepression. The hormone receptor without ligand binding interacts with heat shock proteins and prevents the transcription of targeted genes.
•Aldosterone and cortisol (a glucosteroid) have similar affinity for the mineralocorticoid receptor; however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids. This enzyme, 11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2), catalyzes the deactivation of glucocorticoids to 11-dehydro metabolites. Licorice is known to be an inhibitor of this enzyme and chronic consumption can result in a condition known as pseudohyperaldosteronism.
Steroidogenesis, showing mineralocorticoids in ellipse at top right
Steroidogenesis showing glucocorticoids in green ellipse at right.
•They are produced in the zona fasciculata.
•The primary glucocorticoid released by the adrenal gland in the human is cortisol and corticosterone in many other animals.
•Its secretion is regulated by the hormone ACTH from the anterior pituitary. •Upon binding to its target, cortisol enhances metabolism in several ways:
It stimulates the release of amino acids from the bodyIt stimulates lipolysis, the breakdown of fatIt stimulates gluconeogenesis, the production of glucose from
newly-released amino acids and lipidsIt increases blood glucose levels in response to stress, by inhibiting
glucose uptake into muscle and fat cellsIt strengthens cardiac muscle contractionsIt increases water retentionIt has anti-inflammatory and anti-allergic effects
Mechanism of action
•TransactivationGlucocorticoids bind to the cytosolic glucocorticoid receptor (GR). This type of receptor is activated by ligand binding. After a hormone binds to the corresponding receptor, the newly-formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to glucocorticoid response elements (GRE) in the promoter region of the target genes resulting in the regulation of gene expression. This process is commonly referred to as transactivation.The proteins encoded by these upregulated genes have a wide range of effects including for example:anti-inflammatory – lipocortin I, p11/calpactin binding protein and secretory leukoprotease inhibitor 1 (SLPI)increased gluconeogenesis – glucose-6-phosphatase and tyrosine aminotransferase
•TransrepressionThe opposite mechanism is called transrepression. The activated hormone receptor interacts with specific transcription factors (such as AP-1 and NF-κB) and prevents the transcription of targeted genes. Glucocorticoids are able to prevent the transcription of pro-inflammatory genes, including interleukins IL-1B, IL-4, IL-5, and IL-8, chemokines, cytokines, GM-CSF, and TNFA genes.
DissociationThe ordinary glucocorticoids do not distinguish among transactivation and transrepression and influence both the "wanted" immune and "unwanted" genes regulating the metabolic and cardiovascular functions. Intensive research is aimed at discovering selectively acting glucocorticoids that will be able to repress only the immune system.Genetically modified mice which express a modified GR which is incapable of DNA binding are still responsive to the antiinflammatory effects of glucocorticoids while the stimulation of gluconeogenesis by glucocorticoids is blocked. This result strongly suggests that most of the desirable antiinflammatory effects are due to transrepression while the undesirable metabolic effects arise from transactivation, a hypothesis also underlying the development of selective glucocorticoid receptor agonists.
Androgen, also called androgenic hormones or testoids, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors.
This includes the activity of the accessory male sex organs and development of male secondary sex characteristics.
Androgens were first discovered in 1936.
Androgens are also the original anaboli steroids and the precursor of all estrogens, the female sex hormones.
The primary and most well-known androgen is testosterone.
Androgen ablation can be used as an effective therapy in prostate cancer.
FunctionsDevelopment of the male
•Testes formationDuring mammalian development, the gonads are at first capable of becoming either ovaries or testes. In humans, starting at about week 4 the gonadal rudiments are present within the intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial sex cords develop within the forming testes and incorporate the germ cells as they migrate into the gonads. In males, certain Y chromosome genes, particularly SRY, control development of the male phenotype, including conversion of the early bipotential gonad into testes. In males, the sex cords fully invade the developing gonads.
•Androgen productionThe mesoderm-derived epithelial cells of the sex cords in developing testes become the Sertoli cells which will function to support sperm cell formation. A minor population of non-epithelial cells appear between the tubules by week 8 of human fetal development. These are Leydig cells. Soon after they differentiate, Leydig cells begin to produce androgens.
•Androgen effectsThe androgens function as paracrine hormones required by the Sertoli cells in order to support sperm production. They are also required for masculinization of the developing male fetus (including penis and scrotum formation). Under the influence of androgens, remnants of the mesonephron, the Wolffian ducts, develop into the epididymis, vas deferens and seminal vesicles. This action of androgens is supported by a hormone from Sertoli cells, MIH (Müllerian inhibitory hormone), which prevents the embryonic Müllerian ducts from developing into fallopian tubes and other female reproductive tract tissues in male embryos. MIH and androgens cooperate to allow for the normal movement of testes into the scrotum.
•Early regulationBefore the production of the pituitary hormone luteinizing hormone (LH) by the embryo starting at about weeks 11–12, human chorionic gonadotrophin (hCG) promotes the differentiation of Leydig cells and their production of androgens. Androgen action in target tissues often involves conversion of testosterone to 5α-dihydrotestosterone (DHT).
SpermatogenesisDuring puberty, androgen, LH and FSH production increase and the sex cords hollow out, forming the seminiferous tubules, and the germ cells start to differentiate into sperm. Throughout adulthood, androgens and FSH cooperatively act on Sertoli cells in the testes to support sperm production. Exogenous androgen supplements can be used as a male contraceptive. Elevated androgen levels caused by use of androgen supplements can inhibit production of LH and block production of endogenous androgens by Leydig cells. Without the locally high levels of androgens in testes due to androgen production by Leydig cells, the seminiferous tubules can degenerate resulting in infertility. For this reason, many transdermal androgen patches are applied to the scrotum.
Inhibition of fat depositionMales typically have less adipose tissue than females. Recent results indicate that androgens inhibit the ability of some fat cells to store lipids by blocking a signal transduction pathway that normally supports adipocyte function. Also, androgens, but not estrogens, increase beta adrenergic receptors while decreasing alpha adrenergic receptors- which results in increased levels of epinephrine/ norepinephrine due to lack of alpha-2 receptor negative feedback and decreased fat accumulation due to epinephrine/ norepinephrine then acting on lipolysis-inducing beta receptors.
•Muscle massMales typically have more skeletal muscle mass than females. Androgens promote the enlargement of skeletal muscle cells and probably act in a coordinated manner to function by acting on several cell types in skeletal muscle tissue. One type of cell that conveys hormone signals to generating muscle is the myoblast. Higher androgen levels lead to increased expression of androgen receptor. Fusion of myoblasts generates myotubes, in a process that is linked to androgen receptor levels.
•BrainCirculating levels of androgens can influence human behavior because some neurons are sensitive to steroid hormones. Androgen levels have been implicated in the regulation of human aggression and libido. Indeed, androgens are capable of altering the structure of the brain in several species, including mice, rats, and primates, producing sex differences.
Numerous reports have outlined that androgens alone are capable of altering the structure of the brain, however it is difficult to identify which alterations in neuroanatomy stem from androgens or estrogens, because of their potential for conversion.
•The adrenal medulla is part of the adrenal gland.
•It is located at the center of the gland, being surrounded by the adrenal cortex. •It is the inner most part of the adrenal gland, consisting of cells that secrete epinephrine, norepinephrine, and a small amount of dopamine in response to stimulation by sympathetic preganglionic neurons.
Medulla labeled at bottom right.
•Rather than releasing a neurotransmitter, the cells of the adrenal medulla secrete hormones.
•Composed mainly of hormone-producing chromaffin cells, the adrenal medulla is the principal site of the conversion of the amino acid tyrosine into the catecholamines adrenaline (epinephrine), noradrenaline (norepinephrine), and dopamine.
•Because the ANS exerts direct control over the chromaffin cells the hormone release can occur rather quickly. In response to stressors such as exercise or imminent danger, medullary cells release catecholamines into the blood in a 17:3 ratio of adrenaline to noradrenaline.
•Notable effects of adrenaline and noradrenaline include increased heart rate and blood pressure, blood vessel constriction in the skin and gastrointestinal tract, blood vessel dilation in skeletal muscles, bronchiole dilation, and decreased metabolism, all of which are characteristic of the fight-or-flight response. Release of catecholamines is stimulated by nerve impulses, and receptors for catecholamines are widely distributed throughout the body.
HORMONES OF ADRENAL MEDULLA:
Epinephrine (Also called adrenaline.)This hormone increases the heart rate and force of heart contractions, facilitates blood flow to the muscles and brain, causes relaxation of smooth muscles, helps with conversion of glycogen to glucose in the liver, and other activities
Norepinephrine (Also called noradrenaline.)This hormone has little effect on smooth muscle, metabolic processes, and cardiac output, but has strong vasoconstrictive effects, thus increasing blood pressure.
Epinephrine (also known as adrenaline) is a hormone and neurotransmitter.
It increases heart rate, contracts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system.Chemically, epinephrine is a catecholamine, a monoamine produced only by the adrenal glands from the amino acids phenylalanine and tyrosine.
The term adrenaline is derived from the Latin roots ad- and renes and literally means on the kidney, in reference to the adrenal gland's anatomic location on the kidney.
Epinephrine (Also called adrenaline)
(R)-(–)-L-Epinephrine or (R)-(–)-L-adrenaline
Systematic (IUPAC) name(R)-4-(1-hydroxy-
•Adrenal extracts containing adrenaline were first obtained by Polish physiologist Napoleon Cybulski in 1895.
•These extracts, which he called "nadnerczyna", contained epinephrine and other catecholamines.Japanese chemist Jokichi Takamine and his assistant Keizo Uenaka independently discovered adrenaline in 1900.
•In 1901, Takamine successfully isolated and purified the hormone from the adrenal glands of sheep and oxen.
•Adrenaline was first synthesized in the laboratory by Friedrich Stolz and Henry Drysdale Dakin, independently, in 1904.
OriginMedullary cells are derived from the embryonic neural crest and, as such, are simply modified neurons.In particular, they are modified postganglionic cells of the Autonomic nervous system that have lost their axons and dendrites, receiving innervation from corresponding preganglionic fibers. The cells form clusters around large blood vessels.Moreover, as the synapses between pre- and postganglionic fibers are called ganglia, the adrenal medulla is actually a ganglion of the sympathetic nervous system
Chemical synthesisEpinephrine may be synthesized by the reaction of catechol with chloroacety chloride, followed by the reaction with methylamine to give the ketone, which is reduced to the desired hydroxy compound. The racemic mixture may be separated using tartaric acid.
Formula for the synthesis of adrenaline
Norepinephrine (Also called noradrenaline.)
•Norepinephrine (INN) (abbreviated norepi or NE) or noradrenaline (BAN) (abbreviated NA or NAd) is a catecholamine with multiple roles including as a hormone and a neurotransmitter.
•As a stress hormone, norepinephrine affects parts of the brain where attention and responding actions are controlled.
•Along with epinephrine, norepinephrine also underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle.
•Norepinephrine can also suppress neuroinflammation when released diffusely in the brain from the locus ceruleus.
•When norepinephrine acts as a drug it increases blood pressure by increasing vascular tone through α-adrenergic receptor activation. The resulting increase in vascular resistance triggers a compensatory reflex that overcomes its direct stimulatory effects on the heart, called the baroreceptor reflex, which results in a drop in heart rate called reflex bradycardia.
•Norepinephrine is synthesized from dopamine by dopamine β-hydroxylase. It is released from the adrenal medulla into the blood as a hormone, and is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons. The actions of norepinephrine are carried out via the binding to adrenergic receptors.
OriginsNorepinephrine is released when a host of physiological changes are activated by a stressful event.In the brain, this is caused in part by activation of an area of the brain stem called the locus ceruleus. This nucleus is the origin of most norepinephrine pathways in the brain. Noradrenergic neurons project bilaterally (send signals to both sides of the brain) from the locus ceruleus along distinct pathways to many locations, including the cerebral cortex, limbic system, and the spinal cord, forming a neurotransmitter system.Norepinephrine is also released from postganglionic neurons of the sympathetic nervous system, to transmit the fight-or-flight response in each tissue respectively. The adrenal medulla can also be counted to such postganglionic nerve cells, although they release norepinephrine into the blood.
Norepinephrine degradation. Enzymes are shown in boxes:
Inhibitors of norepinephrine release
acetylcholine muscarinic receptor
norepinephrine (itself)/epinephrine α2 receptor
5-HT 5-HT receptor
adenosine P1 receptor
PGE EP receptor
histamine H2 receptor
enkephalin δ receptor
dopamine D2 receptor
ATP P2 receptor
Stimulators of norepinephrine release
adrenaline β2 receptor
angiotensin II AT1 receptor
DISEASES OF THE ADRENAL GLAND:
In Cushing's syndrome, the level of corticosteroids is excessive, usually from overproduction by the adrenal glands. Cushing's syndrome usually results from a tumor that causes the adrenal glands to produce excessive corticosteroids.
People with Cushing's syndrome usually develop excessive fat throughout the torso and have a large, round face.
Doctors measure the level of cortisol to detect Cushing's syndrome.
Surgery or radiation therapy is often needed to remove a tumor.
•Corticosteroids alter the amount and distribution of body fat. •Excessive fat develops throughout the torso and may be particularly noticeable at the top of the back. •A person with Cushing's syndrome usually has a large, round face (moon face). •The arms and legs are usually slender in proportion to the thickened trunk. •Muscles lose their bulk, leading to weakness. •The skin becomes thin, bruises easily, and heals poorly when bruised or cut.• Purple streaks that look like stretch marks may develop over the abdomen. People with Cushing's syndrome tend to tire easily•Cushing's syndrome tend to tire easily.•High corticosteroid levels over time raise the blood pressure, weaken bones (osteoporosis), and diminish resistance to infections.• The risk of developing kidney stones and diabetes is increased, and mental disturbances, including depression and hallucinations, may occur. •Women usually have an irregular menstrual cycle. •Children with Cushing's syndrome grow slowly and remain short. •In some people, the adrenal glands also produce large amounts of androgens (testosterone and similar hormones), leading to increased facial and body hair in women and balding.
•Treatment depends on whether the problem is in the adrenal glands, the pituitary gland, or elsewhere.
• Surgery or radiation therapy may be needed to remove or destroy a pituitary tumor.
•Tumors of the adrenal gland (usually adenomas) can often be removed surgically.
•Both adrenal glands may have to be removed if these treatments are not effective or if no tumor is present.
•People who have both adrenal glands removed, and many people who have part of their adrenal glands removed, must take corticosteroids for life.
•Tumors outside the pituitary and adrenal glands that secrete excess hormones are usually surgically removed.
•Certain drugs, such as metyrapone, can lower cortisol levels and can be used while awaiting more definitive treatment such as surgery.
•In Addison's disease, the adrenal glands are underactive, resulting in a deficiency of adrenal hormones. •Addison's disease may be caused by an autoimmune reaction, cancer, an infection, or some other disease.•A person with Addison's disease feels weak, tired, and dizzy when standing up after sitting or lying down and may develop dark skin patches.•Doctors measure sodium and potassium in the blood and measure cortisol and corticotropin levels to make the diagnosis.•People are given corticosteroids and fluids.
ADDISON’S DIESEASE - HYPERPIGMENTATION INVOLVING PALM OF THE HAND.
•Addison's disease can start at any age and affects males and females about equally. •In 70% of people with Addison's disease, the cause is not precisely known, but the adrenal glands are affected by an autoimmune reaction (see Autoimmune Disorders) in which the body's immune system attacks and destroys the adrenal cortex.•In the other 30%, the adrenal glands are destroyed by cancer, an infection such as tuberculosis, or another identifiable disease. •In infants and children, Addison's disease may be due to a genetic abnormality of the adrenal glands.
Symptoms•Soon after developing Addison's disease, a person feels weak, tired, and dizzy when standing up after sitting or lying down.• These problems may develop gradually and insidiously. People with Addison's disease develop patches of dark skin. •The darkness may seem like tanning, but it appears on areas not even exposed to the sun. Even people with dark skin can develop excessive pigmentation, although the change may be harder to recognize.• Black freckles may develop over the forehead, face, and shoulders, and a bluish black discoloration may develop around the nipples, lips, mouth, rectum, scrotum, or vagina.Most people lose weight, become dehydrated, have no appetite, and develop muscle aches, nausea, vomiting, and diarrhea. Many become unable to tolerate cold. Unless the disease is severe, symptoms tend to become apparent only during times of stress.
•Periods of hypoglycemia, with nervousness and extreme hunger for salty foods, can occur, particularly in children.•If Addison's disease is not treated, severe abdominal pains, profound weakness, extremely low blood pressure, kidney failure, and shock may occur (adrenal crisis). •An adrenal crisis often occurs if the body is subjected to stress, such as an accident, injury, surgery, or severe infection. Death may quickly follow.
Treatment•Regardless of the cause, Addison's disease can be life threatening and must be treated with corticosteroids and intravenous fluids. •Usually, treatment can be started with hydrocortisone or prednisone (a synthetic corticosteroid) taken by mouth. •However, people who are severely ill may be given cortisol intravenously or intramuscularly at first and then hydrocortisone tablets. •Because the body normally produces most cortisol in the morning, replacement hydrocortisone should also be taken in divided doses, with the largest dose in the morning. Hydrocortisone will need to be taken every day for the rest of the person's life.• Larger doses of hydrocortisone are needed when the body is stressed, especially from an illness, and may need to be given by injection if the person has severe diarrhea or vomiting.•Most people also need to take fludrocortisone tablets every day to help restore the body's normal excretion of sodium and potassium. •Supplemental testosterone is not usually needed, although there is some evidence that replacement with DHEA improves the quality of life. Although treatment must be continued for life, the outlook is excellent.
Function of adrenal medulla:•Rather than releasing a neurotransmitter, the cells of the adrenal medulla secrete hormones.•Notable effects of adrenaline and noradrenaline include increased heart rate and blood pressure, blood vessel constriction in the skin and gastrointestinal tract, blood vessel dilation in skeletal muscles, bronchiole dilation, and decreased metabolism, all of which are characteristic of the fight-or-flight response. Release of catecholamines is stimulated by nerve impulses, and receptors for catecholamines are widely distributed throughout the body.
Functions of adrenal cortex:•It stimulates the release of amino acids from the body.•It stimulates lipolysis, the breakdown of fat.•It increases urinary excretion of potassium ions.•It increases interstitial levels of sodium ions.•It increases water retention and blood volume.•Testes formation•Androgen production.•Spermatogenesis•Inhibition of fat deposition
Thereby we conclude up this topic with a quick review of the ADRENAL GLANDThe adrenal glands produce hormones and other chemicals that are released directly into the bloodstream in response to nerve impulses and hormones produced by other organs.
The cells of the adrenal medulla are actually specialized nerve cells that respond to nerve impulses. These cells release the hormones adrenaline or epinephrine and noradrenaline norepinephrine into the bloodstream in response to stress or danger. Adrenaline serves to increase heart rate and blood pressure and helps the body prepare for a "fight-or-flight" response.
The adrenal medulla is the primary source of adrenaline in the body, a hormone that raises blood pressure, increases the heart rate, and acts as a neurotransmitter (a chemical messenger in the nervous system) when the body is subject to stress or danger.
The adrenal cortex responds to hormones produced elsewhere in the body. The cortex makes up part of the hypothalamic-pituitary-adrenal axis, a major functional unit of the endocrine system. This system controls hormone production that is involved with reactions to stress and regulation of digestion, the immune system, mood and emotions, sexual drive, and energy storage and expenditure.
Other cells in the adrenal cortex produce testosterone and small amounts of estrogen, both necessary for sexual maturation in men and women, and aldosterone, a hormone involved in blood pressure regulation and water and electrolyte balance. Now about he disease…….here we discussed 2 diseases which were….cushing syndrome and addison’s syndrome. These 2 disease are caused due to the increased or the decreased level of adrenal gland…..
The testicle is the male generative gland in animals.
FunctionLike the ovaries to which they are homologous, testes are components of both the reproductive system (being gonads) and the endocrine system (being endocrine glands). The respective functions of the testes are:
producing sperm (spermatozoa)producing male sex hormones of
which testosterone is the best-known
Both functions of the testicle, sperm-forming and endocrine, are under control of gonadotropic hormones produced by the anterior pituitary:
luteinizing hormone (LH)follicle-stimulating hormone
Diagram of male (human) testicles
Transverse section through the left side of the scrotum and the left testis.
Duct system•Under a tough membraneous shell, the tunica albuginea, the testis of amniotes, and some teleost fish, contains very fine coiled tubes called seminiferous tubules.
•The tubules are lined with a layer of cells (germ cells) that from puberty into old age, develop into sperm cells (also known as spermatozoa or male gametes).
•The developing sperm travel through the seminiferous tubules to the rete testis located in the mediastinum testis, to the efferent ducts, and then to the epididymis where newly-created sperm cells mature (see spermatogenesis).
•The sperm move into the vas deferens, and are eventually expelled through the urethra and out of the urethral orifice through muscular contractions.Amphibians and most fish do not possess seminiferous tubules.
•Instead, the sperm are produced in spherical structures called sperm ampullae. These are seasonal structures, releasing their contents during the breeding season, and then being resorbed by the body.
•Before the next breeding season, new sperm ampullae begin to form and ripen.The ampullae are otherwise essentially identical to the seminiferous tubules in higher vertebrates, including the same range of cell types.
Primary Cell TypesWithin the seminiferous tubules Here, germ cells develop into spermatogonia, spermatocytes, spermatids and spermatozoon through the process of spermatogenesis. The gametes contain DNA for fertilization of an ovumSertoli cells - the true epithelium of the seminiferous epithelium, critical for the support of germ cell development into spermatozoa. Sertoli cells secrete inhibin.Between tubules (interstitial cells) Leydig cells - cells localized between seminiferous tubules that produce and secrete testosterone and other androgens important for sexual development and puberty, secondary sexual characteristics like facial hair, sexual behavior and libido, supporting spermatogenesis and erectile function. Testosterone also controls testicular volume.Also present are:Immature Leydig cellsInterstitial macrophages and epithelial cells.
•The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. •Ovaries in females are homologous to testes in males, in that they are both gonads and endocrine glands.
Hormones•Ovaries secrete both estrogen and progesterone.•Estrogen is responsible for the appearance of secondary sex characteristics of females at puberty and for the maturation and maintenance of the reproductive organs in their mature functional state. •Progesterone functions with estrogen by promoting cyclic changes in the endometrium (it prepares the endometrium for pregnancy), as well as by helping maintain the endometrium in a healthy state during pregnancy.
HistologyCell TypesFollicular cells flat epithelial cells that originate from surface epithelium covering the ovarygranulosa cells - surrounding follicular cells have change from flat to cuboidal and proliferated to produce a stratified epitheliumGametesThe outermost layer is called the ovarian surface epithelium (previously known as the germinal epithelium). The tunica albuginea covers the cortex. The ovarian cortex consists of ovarian follicles and stroma in between them. Included in the follicles are the cumulus oophorus, membrana granulosa (and the granulosa cells inside it), corona radiata, zona pellucida, and primary oocyte. The zona pellucida, theca of follicle, antrum and liquor folliculi are also contained in the follicle. Also in the cortex is the corpus luteum derived from the follicles.
The innermost layer is the ovarian medulla. It can be hard to distinguish between the cortex and medulla, but follicles are usually not found in the medulla.
Section of the ovary of a newly born child. Germinal epithelium is seen at top. Primitive ova are seen in their cell-nests. The Genital cord or genital ridge is still discernible in this young child. A blood vessel and an ovarian follicle is also seen
•Progesterone also known as P4 (pregn-4-ene-3,20-dione) is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species.
•Progesterone belongs to a class of hormones called progestogens, and is the major naturally occurring human progestogen.
•Progesterone is commonly manufactured from the yam family, Dioscorea.
•Dioscorea produces large amounts of a steroid called diosgenin, which can be converted into progesterone in the laboratory.
Systematic (IUPAC) namepregn-4-ene-3,20-dione
It raises epidermal growth factor-1 levels, a factor often used to induce proliferation, and used to sustain cultures, of stem cells.It increases core temperature (thermogenic function) during ovulation.It reduces spasm and relaxes smooth muscle. Bronchi are widened and mucus regulated. (Progesterone receptors are widely present in submucosal tissue.)It acts as an antiinflammatory agent and regulates the immune response.It reduces gall-bladder activity.It normalizes blood clotting and vascular tone, zinc and copper levels, cell oxygen levels, and use of fat stores for energy.It may affect gum health, increasing risk of gingivitis (gum inflammation) and tooth decay.It appears to prevent endometrial cancer (involving the uterine lining) by regulating the effects of estrogen.
Estrogens (AmE), oestrogens (BE), or œstrogens, are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone. Their name comes from the Greek words estrus/οίστρος = sexual desire + gen/γόνο = to generate.Estrogens are synthesized in all vertebrates as well as some insects. The presence of these steroids in both vertebrate and insects suggests that estrogenic sex hormones have an ancient history.Estrogens are used as part of some oral contraceptives, in estrogen replacement therapy for postmenopausal women, and in hormone replacement therapy for trans women.Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside the cell, they bind to and activate estrogen receptors which in turn modulate the expression of many genes.
Additionally, estrogens have been shown to activate a G protein-coupled receptor, GPR30
•The three major naturally occurring estrogens in women are estrone (E1), estradiol (E2), and estriol (E3). Estradiol (E2) is the predominant form in nonpregnant females, estrone is produced during menopause, and estriol is the primary estrogen of pregnancy. In the body these are all produced from androgens through actions of enzymes.
•From menarche to menopause the primary estrogen is 17β-estradiol. In postmenopausal women more estrone is present than estradiol.
•Estradiol is produced from testosterone and estrone from androstenedione by aromatase.
•Estrone is weaker than estradiol.
•Premarin, a commonly prescribed estrogenic drug, contains the steroidal estrogens equilin and equilenin, in addition to estrone sulfate but due to its health risk, more genetic estrogen named Progynova (estradiol valerate) are now more often prescribed. There are also estradiol skin patches such as Estraderm (the original brand, introduced in the late 1980s) that offer a completely natural alternative. (A skin patch rather than pill also has the advantage of direct transmission into the blood stream without going through the liver.)
NonsteroidalA range of synthetic and natural substances have been identified that also possess estrogenic activity.
Synthetic substances of this kind are known as xenoestrogens.
Plant products with estrogenic activity are called phytoestrogens.
Those produced by fungi are known as mycoestrogens.
Unlike estrogens produced by mammals, these substances are not necessarily steroids.