Chapter 8: The Endocrine System

Hormones...not just for teenagers

•You have seen how aldosterone plays an important part in water regulation•Most of your body’s processes are regulated by hormones – they are considered to be chemical messengers

•The collective set of these organs that secrete hormones important for homeostatic regulation are known as the ENDOCRINE SYSTEM

Efficient or Inefficient?

•If you think about the fact that the blood is the primary substance in our body that passes through EVERY organ, it makes sense to use it as a transportation vector•Therefore, chemical signals, though inefficient when compared to something like nervous signals in the brain, are useful because very distant parts of the body can communicate with each other•However, the complication is that hormones must travel through the WHOLE body before reaching its target organ

Delay

•This means that most systems controlled by hormones will have lag period of start up and stopping•They are also regulated by very tightly monitored feedback loops in order to stop the secretion of the hormone when it is no longer needed•Most feedback loops in the endocrine system are negative

Basic set up

•If you recall the first lecture on homeostasis, a given organ in the endocrine system will follow a basic feedback loop •Diagrams are often used to describe the mechanism of action for a given hormone

•Others are named according to the hormone involved•There are usually at least two organs involved; a monitoring organ and a target organ, but axes may include more than one organ

MONITORING ORGAN

TARGET ORGAN

TARGET ORGAN

CHANGE

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Types of hormones

•Hormones can be classified into two types based on their chemical structure:

•Based on the chemical structures, each type of hormone has slightly different mechanisms of action and can affect cells through different methods

Steroid hormones: welcome in

•Recall that the cellular membrane is composed of mainly lipids

•Therefore, the release and absorption of steroid hormones are less well regulated, since they have the capacity to exit and enter cells freely•If they can pass through cellular membranes, they can pass through nuclear membranes as well; they are often used to control DNA transcription for this reason

http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter18/animation__mechanism_of_steroid_hormone_action__quiz_1_.html

Protein hormones: knock first

•Protein hormones require more regulation because they cannot easily pass through the cellular membranes to affect cells•Protein hormones must interact with cells via receptors on the surface of the cell

http://highered.mcgraw-hill.com/sites/dl/free/0072421975/196644/second_messengers.html

A noteworthy gland: the pituitary gland•One particular gland that is of great importance in the endocrine system is the pituitary gland•It is located at the base of your brain, just in front of the brain stem

Nervous control

•The pituitary gland is a good example of how the brain directly links into the endocrine system•The brain not only helps monitor the state of the body, but it also acts to synthesize and release hormones that control other hormones•Therefore, the brain itself is an important endocrine organ

Hormone axesThe hormone axes we are going to study will include:Glucagon:Hypothalamic-Pituitary-Adrenal axis:

Hypothalamic-Pituitary-Thyroid axis:

Parathyroid:

Hypothalamic-pituitary-testicular axis:

Hypothalamic-pituitary-ovarian axis:

8.2 Glucose regulation

Glucose regulation

•Because glucose is an essential molecule for cellular survival, its regulation is important•A specific concentration of glucose must be kept in the blood in order for cells to access the glucose they need to function

The pancreas

•Pancreatic tissue contains many different types of cells – each different type is responsible for secreting different substances•The cluster of cells that regulate blood sugar form a structure known as the ISLETS OF LANGERHANDS

Glucagon and insulin

•Insulin and glucagon are antagonistic hormones – they produce opposite effects and work together to balance glucose levels•Insulin acts on cells to increase their permeability to glucose by binding to receptors on the cell surface and helping increase the activity of glucose transporters – this decreases the level of glucose in the blood

Time lag

•Understanding this axis helps us to understand the importance of portion sizes in healthy eating•After a meal, glucose floods your bloodstream – if there is more glucose than can be used immediately by cells, it will be put into storage by the liver, who, due to insulin secretion, will be increasing its uptake of glucose, and therefore, creating more glycogen•Between meals, your “starvation mode” – glucagon is secreted to break down the glycogen stored earlier

Diabetes

•Diabetes occurs when insulin production or response to insulin is compromised•There are two types of diabetes:•Type 1 Diabetes/Juvenile Diabetes/Diabetes Mellitus:

•Type 2 Diabetes/Adult-Onset Diabetes:

Symptoms of Diabetes

•Diabetes results:•Increased urine production and therefore increased loss of water•Increased thirst•Increased glucose secretion in urine and therefore increased glucose levels in urine

Long term complications of diabetes•Peripheral neuropathy – numbness in the extremeties

•There is a thought that the heart is also directly affected by the inability to regulate glucose levels

Treatment

•Type 1 diabetes

•Type 2 diabetes

Gestational Diabetes

•Pregnant mothers are also at risk of developing gestational diabetes•This results in an increased blood glucose level that can affect the baby

8.3 Metabolic control

Metabolism

•Metabolism refers to the sum total of all chemical reactions that maintain a living organism•It is most closely associated with those processes that produce and store energy in the body which would include, in simple terms, the making and breaking of chemical bonds

Metabolic control•The BASAL METABOLIC RATE refers to the rate at which an organism can process energy•This rate refers to the amount of energy that the body uses when at rest

•BMR is different for everyone – this explains why two people that have the same diet may have very different body masses •High BMR usually means that you burn more calories per minute than someone with low BMR

Thyroid gland

•The thyroid gland is a large endocrine gland on its own, but situated on top of the thyroid are 4 individual glands that collectively make up the parathyroid gland•The thyroid gland secretes very powerful steroid hormones that control metabolism

Thyroid gland

•Two hormones, T3 and T4, are secreted by the thyroid gland – collectively known as Thyroxine•The “3” and “4” refer to the positions of iodine which are bound to the molecule

Hypothalamic-Pituitary-Thyroid axis

TRH= Thyroid releasing hormone

TSH = Thyroid stimulating hormone

Thyroid disorders•Because iodine is an essential part of the T3 and T4 molecule, a lack of iodine can lead to the underproduction of these hormones•If T3 and T4 are not being secreted, the hypothalamus will not receive negative feedback; therefore, it will continually secrete TRH•This will cause the anterior pituitary to continually secrete TSH•TSH stimulates the thyroid to secrete T3 and T4 – and to do meet the constant demand, the thyroid will increase in size (by increasing the number of secreting cells)

Hyper and Hypothyroidism•An over or undersecretion of thyroxine can lead to a change in BMR•Hyperthyroidism refers to an oversecretion of thyroxine which can lead to rapid weight loss, heightened state of agitation and nervousness, difficulty focusing

•The cause can be a tumour (for example, tumour blocks the exit duct for the hormone) and it is common with aging as cells begin to slow down

Calcium balance

•The parathyroid glands, along with the thyroid gland, work together to balance calcium levels in the blood•Parathyroid hormone (PTH) is secreted by the parathyroid gland and is antagonistic to Calcitonin, secreted by the thyroid gland

Calcitonin and PTH

•Low levels of blood Ca stimulate the release of PTH •PTH increases blood Ca by stimulating the activity of osteoclasts, bone cells that break down bone•This will lead to the release of Ca into the blood stream

Problems with Ca balance

•Improper Ca blood levels can affect bone and muscle•If Ca levels cannot be maintained at normal values, this can affect the amount of available Ca to bones for normal development

Human Growth Hormone

•HGH is an important hormone required for growth in young children•Think carefully about what happens to appetite during adolescence: growing children require large amounts of energy in order to fuel muscle, bone and neuronal development

Secretion•HGH is secreted by the anterior pituitary•Its secretion is controlled by the hypothalamus that secretes GHRH (growth hormone releasing hormone)•HGH acts on the liver to secrete hormones such as IGF (Insulin like growth factor) that acts on muscles to increase hypertrophy (increase in size of cells) and hyperplasia (increase in number of cells) of muscle

IGF

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Actions•GH will also:

• Mobilize fat stores by increasing the breakdown of fat

• Stimulate the growth of internal organs

• Stimulate immune system

Problems with GH•Lack of GH secretion has a much more severe effect during childhood than adulthood•Low GH levels during development will lead to shorter statures and smaller builds in children•This can be a cause of dwarfism –

•Too much GH secretion during childhood can result in the opposite – gigantism –

•Oversecretion of GH in adulthood can cause increased body mass and bone thickness which can interfere with normal skeletal movements – creating a condition called acromegaly

8.4 The stress response

The stress response•Human response to stress is a very important evolutionary mechanism that has evolved to keep us alive•It is controlled by the hypothalamus

•Therefore the first cues that a stress response is necessary due to a threat of danger would be processed through the brain, usually via visual information (as primates are reliant heavily on vision as a sense)

If you’re in danger, then what?•To understand the mechanism better, it is important to understand what happens physiologically in times of danger •This group of symptoms is associated with what biologists refer to as the “flight or fight” response:

The players: the adrenal gland•Divided into two main parts:

•The medulla is innervated directly by the brain via the spinal cord, and the cortex is affected by hormones secreted by the anterior pituitary•The adrenal gland secretes three hormones to produce this group of responses:

Hormone Secreted from Function

Increase in:Blood glucoseHeart rateBreathing rateCellular metabolismConstriction of blood vessels to redirect blood flow to muscles and heart

Increase in:Na+ and water retention in kidneysBlood volumeBlood pressure

Increase in blood glucoseConversion of fats and proteins into glucoseSupression of inflammatory response in immune systemSee p. 382 from

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The players: hypothalamus and the anterior pituitary gland•The brain identifies a stressful situation and signals the adrenal cortex directly; this initiates a short term stress response

•This branch of the axis produces a more long term stress response

SPINAL CORD

BRAIN

HYPOTHALAMUSANTERIOR PITUITARY

ADRENAL GLANDSCORTEX MEDULLA

ADRENALINE AND NORADRENALINE MINERALCORTICOI

DS

GLUCOCORTICOIDS

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The stress response and health•It is easy to see why stressful lives can lead to long term health problems; remember that human society has changed what our “stress” is•Previously, our response to danger was physical, and so the stress response prepares our bodies for that•Now, due to changes in human society, most stress responses are emotional or neurological – the final exam, death in the family, the big deadline at work•Someone who is consistently in a state of stress will be creating physiological conditions where blood pressure is pushed past normal•This can stress the heart and lead to the increased risk of cardiovascular disease throughout one’s lifetime if coupled with poor lifestyle choices

8.5 Reproductive hormones

The hormones that make teens famous•Reproductive hormones in males and females are focused on regulating reproductive processes•In males: this affects the production of sperm•In females: this affects the menstrual cycle which regulates the release of ova from the ovaraies each month

The male reproductive system

•The main hormone responsible for regulating the male reproductive system is testosterone•Testosterone is secreted by the interstitial cells which are found within the testicles

Male reproductive anatomy

•In males, the urinary and reproductive systems are linked•Both sperm and urine exit out of the urethra •The testicles contain a series of very coiled and very thin tubes known as the seminiferous tubules

Male reproductive anatomy cont.

•From there, sperm exits the epididymis through the vas deferens •The vas deferens is connected to 3 major glands: •Prostate gland:

•Cowper’s gland:

•Seminal vesicle:

Male reproductive hormones•Testosterone production and secretion is controlled by a negative feedback loop that includes the hypothalamus and the anterior pituitary gland along with the testicles•GnRH (gonadotropin releasing hormone) is secreted by the hypothalamus

•FSH acts on sertoli cells and LH acts on interstitial cells (AKA: Leydig cells)•LH signals interstitial cells to secrete testosterone

Hypothalamic-Pituitary-Testicular axis

(Interstitial cells)

Testosterone’s other effects•Testosterone will increase hair growth, muscle hypertrophy (helps males increase muscle size), and increase aggression •Testosterone secretion during puberty causes the larynx to lengthen, thus deepening the male voice, maturation of the penis and the development of pubic hair•Excess testosterone secretion can lead to increased aggression

Female Reproductive anatomy

•In women, the reproductive system is separated from the urinary system •This is an obvious adaptation as both systems need to remain separate for the gestation of offspring•The ovaries are the main hormone producing structure (along, ofcourse, with the development and storing of ova or eggs)

Horomone regulation

•Once past puberty, females release one egg per month (usually – though sometimes more than one can be released) •The 27 day cycle is based on the release of the egg, the preparation of the uterine lining for pregnancy, and the shedding of the lining if pregnancy doesn’t occur

Oogenesis•Unlike men, women are born with all their eggs•The eggs are stored in the ovary within structures called follicles

•Therefore, older ova that have been exposed to more radiation/chemicals are at higher risk of having chromosomal anomalies that can lead to congenital birth defects

The menstrual cycle

•Hormone fluctuations are timed around the release of the ova•The menstrual cycle is timed from the start of menses (period) when the uterine lining is shed

Follicular phase•The hypothalamus releases GnRH that stimulates the anterior pituitary to release FSH (Follicle stimulating hormone)•The developing follicle then secretes estrogen

•The peak of estrogen secretion at ovulation feeds back positively on the anterior pituitary to secrete LH (Luteinizing hormone)

Ovlulation•When the follicle is mature, a spike in LH (Luteinizing homone) secreted by the Anterior pituitary stimluates the follicle to rupture and release the ovum

•By now, the uterine lining has thickened in case the ovum is fertilized in the fallopian tube and is ready for implantation when it reaches the uterus

Luteal phase

•The developing Corpus Luteum secretes some estrogen but mainly progesterone•Progesterone helps to maintain the uterine lining, keeping it ready for implantation

•This prevents the maturation and release of any further follicles

Pregnant or not?

•If no fertilization occurs, the corpus luteum will die due to the lack of FSH and LH•Once the corpus luteum dies, production of estrogen and progesterone stops•This will remove the negative feedback on the hypothalmus and anterior pituitary leading to the secretion of FSH and LH to restart the cycle

See p. 398 for Hypothalamic – pituitary – ovarian axis

Pregnancy•If the ovum is fertilized, the developing placenta will secrete hormones to maintain itself•hCG (human chorionic gonadotrophin) is secreted to supress the regression of the corpus luteum – this keeps it alive to prevent levels of progesterone and estrogen from falling•The detection of hCG is the basis of the pregnancy test

PMS•All men make fun of it, and some women do – but it is important to respect the effect of hormonal fluctuations in women

•PMS is used to describe the effect of these hormones on the brain before menses when their concentrations are high•In some women, the brain’s response to the hormones is so severe that it can stimulate severe depression leading to suicidal tendencies or even overt aggression

Menopause

•Women between the ages of 46-54 will enter into Menopause (yes, the name literally tells you what is going on) where ovaries lose their sensitivity to FSH and LH

•It is interesting to note that menopause is rare in most animal species

Women aren’t so much from Venus and Men aren’t so much for Mars

•Testosterone, progesterone and estrogen are steroid based hormones that can be converted into each other via common biochemical pathways•It is worthwhile to note that women do have testosterone and men do have estrogen – however, the levels of these hormones are very small

Over or undersecretion•Under or oversecretion of any of testosterone in women or estrogen in men can result in masculinization or feminization of physical features

•These hormones are very powerful and can cause these effects even after puberty