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Control of Secretion Rate Most hormones controlled by negative feedback
systems Most hormones are not secreted at constant rate,
but their secretion is regulated by three differentmethods1. The action of a substance other than a hormone on an
endocrine gland.
2. Neural control of endocrine gland.3. Control of secretory activity of one endocrine gland by hormone or neurohormone secreted by anotherendocrine gland
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1. Humoral stimulus: Action of Substance
Other Than Hormone An increased blood glucose
concentration stimulatesincreased insulin secretion fromthe pancreas
Insulin increases glucose uptake by tissues, which decreases blood glucose levels.
Autonomic nervous system alsoinfluences insulin secretion
Hypocalcemia stimulates PTHsecretion from parathyroids
Hypersecretion stimulatescalcitonin from parafollicularcells
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2. Nervous System Regulation
Stimuli such as stress orexercise activate thesympathetic division of theautonomic nervous system
Sympathetic neurons stimulate
the release of epinephrine andsmaller amounts ofnorepinephrine from the adrenalmedulla. Epinephrine andnorepinephrine prepare the
body to respond to stressfulconditions.
Once the stressful stimuli areremoved, less epinephrine isreleased as a result of decreasedstimulation from the autonomicnervous system.
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Positive and Negative Feedback
POSITIVE During the menstrual cycle, before
ovulation, small amounts ofestrogen are secreted from theovary.
Estrogen stimulates the release ofgonadotropin-releasing hormone(GnRH) from the hypothalamusand luteinizing hormone (LH)from the anterior pituitary
GnRH also stimulates the releaseof LH from the anterior pituitary
LH causes the release of additional
estrogen from the ovary. TheGnRH and LH levels in the bloodincrease because of this positive-feedback effect.
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Positive and Negative FeedbackNEGATIVE
During the menstrual cycle,after ovulation, the ovary begins to secrete progesterone in response toLH.
Progesterone inhibits therelease of GnRH from thehypothalamus and LH fromthe anterior pituitary.
Decreased GnRH releasefrom the hypothalamusreduces LH secretion fromthe anterior pituitary. GnRHand LH levels in the blooddecrease because of thisnegative-feedback effect.
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Changes in Hormone SecretionThrough Time
a) Chronic hormone regulation.Maintenance of relativelyconstant concentration ofhormone. Thyroid hormone.
b) Acute hormone regulation.Epinephrine in response tostress.
c) Cyclic hormone regulation.Female reproductive
hormones.
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Transport andDistribution Hormones dissolve in blood plasma andare transported in free form or are
reversibly bound to plasma proteins Free form can diffuse from plasma into
interstitial fluid and affect cells As concentration of free hormone
molecules increase, more hormonesmolecules diffuse from capillaries intointerstitial spaces to bind to target cells
Lipid soluble hormones diffuse throughcapillary cells. Water soluble hormonesdiffuse through pores in capillaries calledfenestrae.
A large decrease in plasma proteinconcentration can result in loss of ahormone from the blood because freehormones are rapidly eliminated fromcirculation through kidney or liver
Hormones are distributed quickly becausethey circulate in the blood
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Metabolism and Excretion
Half-life : The length oftime it takes for half adose of substance to beeliminated fromcirculatory system
Long half-life: regulateactivities that remain ata constant rate throughtime. Usually lipidsoluble and travel in
plasma attached to proteins
Short half-life: water-soluble hormones as proteins, epinephrine,norepinephrine. Have arapid onset and shortduration
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Hormone (Ligand) Interaction with TargetTissues
Portion of molecule where ligand binds is called binding site .
If the molecule is a receptor (like ina cell membrane) the binding site iscalled a receptor site
Ligand/receptor site is specific ; e.g.,epinephrine cannot bind to thereceptor site for insulin.
The purpose of binding to targettissue is to elicit a response by thetarget cell.
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Down-Regulation
Normally, receptor molecules aredegraded and replaced on aregular basis.
Down-regulation Rate at which receptors are
synthesized decreases in some cellsafter the cells are exposed to aligand.
Combination of ligands andreceptors can increase the rate atwhich receptor molecules aredegraded. This combined form istaken into the cell by phagocytosisand then broken down.
Tissues that exhibit down-regulation are adapted to short-term increases in hormoneconcentration.
Tissues that respond to hormonesmaintained at constant levelsnormally do not exhibit down-regulation.
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Up-Regulation Some stimulus causes increase
in synthesis of receptors for ahormone, thus increasessensitivity to that hormone
For example, FSH stimulationof the ovary causes an increaseof LH receptors. Ovarian cellsare now more sensitive to LH,even if the concentration of LHdoes not change. This causesovulation.
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Membrane-Bound Receptors Receptor: integral proteins with
receptor site at extracellular surface.Interact with ligands that cannot passthrough the plasma membrane.
Ligands Water-soluble or large-molecular-
weight hormones. Attachment ofligand causes intracellular reaction. Large proteins, glycoproteins,
polypeptides; smaller moleculeslike epinephrine andnorepinephrine
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Intracellular Receptors Receptors: in the cytoplasm or
in the nucleus Ligands Lipid soluble and
relatively small molecules; pass through the plasma
membrane. React either with enzymesin the cytoplasm or withDNA to causetranscription andtranslation
Thyroid hormones,testosterone, estrogen,
progesterone, aldosterone,and cortisol
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Membrane-Bound Receptors Proteins or glycoproteins that have polypeptide chains
folded to cross cell membrane several times Ligand binds reversibly to receptor site on receptor
protein Three different results of ligand binding
1. Alteration of membrane permeability . Example:acetylcholine2. Activation of G proteins associated with the
membrane, causes production of intracellular mediatorsuch as cyclicAMP, leads to activation of intracellular
enzymes. Example: LH3. Receptors linked to intracellular enzymes through intracellular mediators . Mediators alter activity ofintracellular enzymes. Examples: nitric oxide,cyclicGMP, Ca ions.
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Intracellular Receptors Proteins in cytoplasm or nucleus Hormones bind with intracellular receptor and
receptor-hormone complex activate certain genes,causes transcription of mRNA and translation.These proteins (enzymes) produce the response ofthe target cell to the hormone
Latent period of several hours because time isrequired to produce mRNA and protein
Processes limited by breakdown of receptor-
hormone complex Estrogen and testosterone produce different proteins in cells that cause the differing secondarysexual characteristics of females and males.
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Anatomy and Physiology, Seventh Editi on
Rod R. Seeley Idaho State UniversityTrent D. Stephens
Idaho State UniversityPhilip Tate
Phoenix College
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
*See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes.
Chapter 18
Lecture Outline *
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Endocrine System Functions
Metabolism and tissue maturation Ion regulation
Water balance Immune system regulation Heart rate and blood pressure regulation Control of blood glucose and other nutrients
Control of reproductive functions Uterine contractions and milk release
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Pituitary Gland andHypothalamus
Where nervous andendocrine systems interact
Hypothalamus regulatessecretions of anterior
pituitary Posterior pituitary is anextension of thehypothalamus
Anterior pituitary producesnine major hormones that Regulate body functions Regulate the secretions of
other endocrine glands
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Pituitary Gland Structure
Posterior pituitary (neurohypophysis ): extensionof the nervous system via theinfundibulum Secretes neurohormones
Anterior pituitary (adenohypophysis ) Consists of three areas with
indistinct boundaries: parsdistalis, pars intermedia, parstuberalis
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Hypothalamus, Anterior Pituitary, and Target Tissues
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Releasing and Inhibiting Hormones Tropins or tropic hormones : hormones that regulate the hormone secretions
of target endocrine tissues. All anterior pituitary hormones are tropins. Releasing hormones secreted by the hypothalamus:
GHRH . Growth hormone-releasing hormone . Causes the anterior pituitary to release growth hormone.
TRH . Thyroid-releasing hormone . Causes the anterior pituitary torelease thyroid-stimulating hormone (TSH).
CRH . Corticotropin-releasing hormone . Causes anterior pituitary to
produce adrenocorticotropic hormone (ACTH) GnRH . Gonadotropin-releasing hormone . Causes anterior pituitary to produce FSH (follicle stimulating hormone) and LH (luteinizinghormone).
PRH . Prolactin-releasing hormone . Causes the anterior pituitary torelease prolactin.
Inhibiting hormones: GHIH . Growth hormone-inhibiting hormone , somatostatin . Causes
the anterior pituitary to decrease release of growth hormone. PIH . Prolactin-inhibiting hormone . Causes the anterior pituitary to
decrease release of prolactin.
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Hypothalamus, Posterior Pituitary and TargetTissues
Hypothalamic neuronssyntheisze ADH andoxytocin. Latter hormones travelto post. pituitary viaaxons of hypothalamicneurons. ADH and oxytocinenter circulation in post.
pituitary.
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Hormones of Posterior Pituitary: ADH
Antidiuretic hormone (ADH). Also called vasopressin.A. Osmoreceptors (specialized neurons of
hypothalamus monitor changes in intercellularosmolality (relative concentrations of electrolytes andwater). If the concentration of electrolytes increases
or if the concentration of water decreases, then ADHsecretion is stimulated.
B. Baroreceptors (specialized neurons found in walls ofatria of heart, large veins, carotid arteries, aortic arch)
sense changes in blood pressure (BP). If BPdecreases, then ADH secretion is stimulated.
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Control of ADH Secretion
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Control of Oxytocin Secretion
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Anterior Pituitary Hormones Growth hormone (GH) or somatotropin Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH)
Melanocyte-stimulating hormone(MSH) Beta endorphins Lipotropins Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) Prolactin
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Growth Hormone (GH or somatotropin)
Stimulates uptake of amino acids; proteinsynthesis; growth in most tissues.
Stimulates breakdown of fats to be used asan energy source but stimulates synthesis ofglycogen: glucose sparing
Promotes bone and cartilage growth
Regulates blood levels of nutrients after ameal and during periods of fasting Stimulates glucose synthesis by liver
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Figure 16.6
Metabolic Action of Growth
Hormone
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Growth Hormone Stimulation: functions in
regulating growth, tissue maintenance, metabolismGHRH from hypothalamus causes release of
Growth hormone from anterior pituitary effects Target tissues : most tissues of the body
Direct effect: GH binds to receptors on cells and causeschanges within the cells. Increased lipolysis and decreaseduse of glucose for energy
Indirect effect: causes liver and skeletal muscle to produce
somatomedins; e.g., insulinlike growth factors (IGFs) Insulinlike growth factors: bind to receptors on
membranes of target cells. Stimulate growth incartilage, bone; increased synthesis of proteins inskeletal muscle.
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Regulation of GH Secretion1. Stress and decreased glucose
levels increase release of GHRHand decrease release of GHIH.
2. GHRH and GHIN travel viathehypothalamohypophyseal
portal system to ant. pituitary3. Increased GHRH and reduced
GHIH act on AP and result inincreased GH secretion.
4. GH acts on target tissues.5. Increasing GH levels have neg
feedback effect on hypothala.
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Growth Hormone: Inhibition
Hypothalamus produces growth hormone inhibitinghormone (GHIH = somatostatin)
Inhibits production of GH by anterior pituitary.
GHRH secretion in response to low blood glucose, stress,increase in certain a.a.
GHIH secretions in response to high blood glucose. Peak GH levels during deep sleep; levels lower at other
times of day. Hyposecretion of GH may result in dwarfism Hypersecretion may result in giantism or acromegaly de-
pending on ossification of epiphyseal plates
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TSH and Thyroid Hormones
TRH from hypothalamus causes the releaseof TSH from anterior pituitary which
causes secretion and storage of hormonesT 3 and T 4 from and within the thyroid gland TSH increases activity of phospholipase
that opens Ca 2+ channels, increasing Ca 2+ concentration in cells of the thyroid gland
T3 and T4 inhibit TRH and TSH secretion
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Adrenocorticotrophic Hormone (ACTH)
CRH from hypothalamus causes release ofACTH from anterior pituitary which
Causes cortisol secretion from the adrenalcortex (a glucocorticoid from the zonafasciculata)
Causes aldosterone secretion from theadrenal cortex (a mineralocorticoid from
the zona glomerulosa) Binds directly to melanocytes of the skin;
causes increase in production of melanin.
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Melanocyte Stimulating Hormone,
Endorphins, and Lipotropins ACTH , MSH , endorphins and lipotropins all derived
from the same large precursor molecule when stimulated by CRH
MSH causes melanocytes to produce more melanin Endorphins act as an analgesic; produced during times of
stress. Lipotropins cause adipose cells to catabolize fat
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LH, FSH, Prolactin
Gonadotrophs : glycoprotein hormones that promotegrowth and function of the gonads LH and FSH
Both hormones regulate production of gametes and
reproductive hormones Testosterone in males Estrogen and progesterone in females
GnRH from hypothalamus stimulates LH and FSH
secretion Prolactin : role in milk production
Regulation of secretion: prolactin-releasing hormone (PRH)and prolactin-inhibiting hormones (PIH)
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ThyroidGland
One of largest endocrine glands; Highlyvascular. Iodine enters follicular cells by activetransport. Only gland that stores hormone.
Histology Composed of follicles : follicular cells
surrounding thyroglobulin/thyroidhormones
Parafollicular cells : between follicles
Physiology Follicular cells secrete thyroglobulin intolumen of follicle. Iodine and a.a. tyrosinenecessary for production of T3 and T4.Hormones stored here attached to thethyroglobulin then absorbed into follicular
cells; hormones disattached fromthyroglobulin and released into circulation. Parafollicular cells. Secrete calcitonin
which reduces [Ca2+] in body fluids whenCa levels are elevated.
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Biosynthesis of ThyroidHormones
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Thyroid Hormones Produced by follicular cells
Triiodothyronine or T 3 -less produced Tetraiodothyronine or T 4 or thyroxine- more
99.6% of thyroxine in the blood is bound to thyroxine- binding globulin (TBG) from the liver. Rest is free.
TBG has a higher affinity for T4
than for T3; amt of free
unbound T 3 in plasma is 10xs greater than free T 4. Only free thyroxine and T 3 can enter cells; bound-
thyroxine serves as a reservoir of this hormone 33-40% of T 4 converted to T 3 in cells: T 3 more potent
Bind with intracellular receptor molecules and initiatenew protein synthesis Increase rate of glucose, fat, protein metabolism in
many tissues thus increasing body temperature Normal growth of many tissues dependent on presence
of thyroid hormones.
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Effects of T 3 and T 4 1. Maintain normal rate of metabolism.
2. Increase the rate at which glucose, fat, and protein are meta- bolized.3. Increase the activity of Na +-K + pump which increases body
temperature.4. Can alter the number and activity of mitochondria resulting in
greater ATP synthesis and heat production.5. Normal growth and maturation of bone, hair, teeth, c.t., and
nervous tissue require thyroid hormone.6. Both T 3 and T 4 play a permissive role for GH and GH does not
have its normal effect on tissues if T 3 and T 4 are lacking.7. See Table 18.4 for effects of hypo- and hypersecretion
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Regulation of T 3 and T 4 Secretion
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Regulation of Calcitonin Secretion
Produced by parafollicular cells Secretion triggered by high Ca 2+
concentration in blood; acts to decreaseCa 2+ concentration
Primary target tissue: bone. Decreasesosteoclast activity, lengthens life spanof osteoblasts.
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Parathyroid Glands Embedded in thyroid
Two glands on each side Secrete PTH: target tissues are bone, kidneys and intestines.
Increases blood calcium and phosphate levels
Stimulates osteoclasts Promotes calcium reabsorption by
kidneys and PO4 excretion Increases synthesis of vitamin D
which, in turn, increases absorptionof Ca and PO4 by intestines. Netloss of PO4 under influence of
PTH. Regulation depends on calcium
levels.
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Figure 16.11
Effects of Parathyroid Hormone
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Adrenal Glands Near superior poles of
kidneys; retroperitoneal Inner medulla; outer
cortex
Medulla: formed fromneural crest; sympathetic.Secretes epinephrine andnorepinephrine
Cortex: three zones fromsuperficial to deep Zona glomerulosa Zona fasciculata Zona reticularis
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Adrenal Medulla Secretory products are neurohormones: epinephrine and norepinephrine
Combine with adrenergic membrane-bound receptors All function through G protein mechanisms Secretion of hormones prepares body for physical activity Effects are short-lived; hormones rapidly metabolized Epinephrine
Increases blood levels of glucose Increases fat breakdown in adipose tissue Causes dilation of blood vessels in skeletal muscles and cardiac muscles.
Epinephrine and norepinephrine increase heart rate and force of contraction;cause blood vessels to constrict in skin, kidneys, gastrointestinal tract, and
other viscera
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Hormones of Adrenal Cortex Mineralocorticoids : Zona glomerulosa
Aldosterone produced in greatest amounts. Increasesrate of sodium reabsorption by kidneys increasingsodium blood levels
Glucocorticoids : Zona fasciculata
Cortisol is major hormone. Increases fat and protein breakdown, increases glucose synthesis, decreasesinflammatory response
Androgens : Zona reticularis
Weak androgens secreted then converted to testosterone by peripheral tissues. Stimulate pubic and axillary hairgrowth and sexual drive in females
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Regulation of Cortisol Secretion
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Help the body resist stress by: Keeping blood sugar levels relatively constant
Maintaining blood volume and preventing water shiftinto tissue
Cortisol provokes: Gluconeogenesis (formation of glucose from
noncarbohydrates) Rises in blood glucose, fatty acids, and amino acids
Glucocorticoids (Cortisol)
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Figure 16.15
Stress and the Adrenal Gland
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Pancreas Located along small intestine and
stomach; retroperitoneal Exocrine gland
Produces pancreatic digestive juices
Endocrine gland Consists of pancreatic islets Composed of
Alpha cells ; secrete glucagon Beta cells ; secrete insulin Delta cells ; secrete somatostatin
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A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent
Its major target is the liver, where it promotes: Glycogenolysis the breakdown of glycogen to
glucose Gluconeogenesis synthesis of glucose from lactic acid
and noncarbohydrates Release of glucose to the blood from liver cells
Glucagon
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Target tissue is the liver, adipose tissue, muscle,and satiety center of hypothalamus
A 51-amino-acid protein consisting of two aminoacid chains linked by disulfide bonds
Synthesized as part of proinsulin and then excised by enzymes, releasing functional insulin
Insulin:
Lowers blood glucose levels Enhances transport of glucose into body cells Counters metabolic activity that would enhance blood
glucose levels
Insulin
Regulation of Blood Glucose Levels
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Regulation of Blood Glucose Levels
Thehyperglycemic
effects ofglucagon andthe
hypoglycemiceffects ofinsulin
Figure 16.17
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Results from hyposecretion or hypoactivity ofinsulin
The three cardinal signs of DM are: Polyuria huge urine output Polydipsia excessive thirst Polyphagia excessive hunger and food consumption
Hyperinsulinism excessive insulin secretion,resulting in hypoglycemia
Diabetes Mellitus (DM)
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Figure 16.18
Diabetes Mellitus (DM)
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Regulation of Insulin Secretion
R l i f Bl d N i L l
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Regulation of Blood Nutrient Levels
Regulation of Blood Nutrient Levels
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Regulation of Blood Nutrient LevelsDuring Exercise
H f th R d ti S t
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Hormones of the Reproductive System
Male: Testes Testosterone
Regulates production of spermcells and development andmaintenance of malereproductive organs andsecondary sex characteristics
Inhibin Inhibits FSH secretion
Female: Ovaries Estrogen and Progesterone
Uterine and mammary glanddevelopment and function,external genitalia structure,
secondary sex characteristics,menstrual cycle
Inhibin Inhibits FSH secretion
Relaxin
Increases flexibility ofsymphysis pubis
Pineal Body
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Pineal Body In epithalamus; produces melatonin and arginine
vasotocin
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Thymus Gland, GI Tract, Kidneys
Thymosin. Development of the immunesystem. GI tract: several hormones regulate
digestion and enzyme secretion. Studiedwith digestive system.
Kidneys secrete erythropoietin, whichsignals the production of red blood cells
Adipose tissue releases leptin, which isinvolved in the sensation of satiety, andstimulates increased energy expenditure
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Hormone-like Substances Autocrines : chemical signals released by a cell and the
substance affects that same cell. Chemical mediators of inflammation which are
modified fatty acids: eicosanoids such as prostaglandins, thromboxanes, prostacyclins, andleukotrienes
Paracrines : chemical signals released into intercellularfluid and affecting nearby cells. Endorphins and enkephalins modulate sensation of pain Several growth factors
Effects of Aging on
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Effects of Aging onEndocrine System
Gradual decrease in secretory activity of some glands GH as people age except in people who exercise regularly Melatonin
Thyroid hormones Kidneys secrete less renin
Familial tendency to develop type II diabetes