Endocrine Physiology

ENDOCRINE PHYSIOLOGY

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Types of Regulatory Molecules  Hormone

– A regulatory chemical secreted into the blood by an endocrine gland, or an organ exhibiting endocrine function.  Target Cells respond to hormone 

Neurohormone – A chemical messenger secreted by neuron into the blood rather than the synaptic cleft.

 Paracrine

- regulatory molecules work without being transmitted by the blood – not endocrine 2

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HORMONES

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PARACRINE

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NEUROHORMONES

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Types of hormones

within the membrane, binds to the receptors on the outside of membrane; its effects are the most rapid of all the hormones

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receptor response as protein hormones i. Epinepherine ii. Norepinepherine iii. Thyroid hormones iv. Melatonin

c. Steroid hormones – binds to the intracellular receptors; slow actions i. Gonadal hormones Estrogen, progesterone, androgens .1 ii. Adrenal hormones Glucocorticoids, mineralocorticoids .1 8

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RECEPTORS        

RECEPTORS: 1. Surface receptors a. Channel linked b. G protein c. Enzyme linked 2. Intracellular receptors a. Cytoplasmic b. Nuclear 9

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Hormones are Extremely Powerful

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Hormones That Enter Cells  Fat

soluble hormones pass through the target cell’s plasma membrane and bind to intracellular receptor proteins. 

hormone receptor complex then binds to specific regions of DNA   

activate genes and regulate target cells Steroid hormones binds cytoplasmic receptors Thyroid hormone binds nuclear receptors

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Steroid Hormone Action

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Hormones That Do Not Enter Cells  Hormones

that are too large or too polar to cross plasma membranes include all of the peptide and glycoprotein hormones, as well as catecholamine hormones epinephrine and norepinephrine. 

bind to receptor proteins located on the outer surface of the plasma membrane  

cyclic AMP second-messenger system IP3/CA++ second-messenger system 15

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Action of Epinephrine on a 1. Epinephrine is water soluble Liver Cell

and needs to bind to specific receptor proteins on cell surface. 2. Acting through intermediary G proteins the hormone bound receptor activates the enzyme adenenyl cyclase which converts ATP to cAMP 3. Cyclic AMP performs as a 2ndary messenger and activates protein kinase-A an enzyme that was previously inactive 4. Protein kinase–A phosphorylates and activates the enzyme phosphorylase which catalyses the hydrolysis of glycogen into glucose. 16

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IP3/CA++ Second-Messenger System 1. The hormone epinephrine binds to specific receptor proteins on the cell surface. 2. Acting through G- proteins, the hormone-bound receptor activates the enzyme phospholipase C, which converts membrane phospholipids into inositol triphosphate (IP3) 3. IP3 diffuses thru the cytoplasm and binds to receptors on the endoplasmic reticulum 4. The binding of IP3 to the receptor stimulates the endoplasmic reticulum to release Ca++ into the cytoplasm 5. Some of the released Ca++ binds to the receptor protein called calmodulin 6. The Ca++/Calmodulin complex activates other intracellular proteins – producing the 17 17 hormone effects

Endocrine Glands and Hormones 

Neural and endocrine interactions 



Endocrine system also interacts and cooperates with the nervous system to regulate the activities of the other organ systems of the body. Secretory activity of many endocrine glands controlled by nervous system like  Adrenal medulla, posterior pituitary, and pineal gland  major site for neural regulation is the brain’s regulation of the anterior pituitary by the hypothalmus However many are not under neural control

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Pituitary & all Hormones are Under the Control of the Hypothalamus Hypothalamus RF Anterior Pituitary SH Target Organs

Hormone Posterior Pituitary Hormone Target Organs

RF = Releasing Factor SH = Stimulating Hormone 19

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Negative Feedback Inhibition

Hormones secreted by some endocrine glands feed back to inhibit the secretion of hypothalamic releasing hormones and anterior 21 21 pituitary hormones

Feedback control

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Human Endocrine System major glands

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Anterior Pituitary Gland 

Develops from a pouch of epithelial tissue that pinches off the roof of the embryo’s mouth.  produces the hormones it secretes:       

growth hormone (GH) stimulates muscles and bones to grow adrenocorticotropic hormone (ACTH) regulates corticosteroid secretion thyroid-stimulating hormone (TSH) stimulates the production of thyroxin by thyroid gland luteinizing hormone (LH) ovulation and testosterone production in testes follicle-stimulating hormone (FSH) develops ovarian follicle and sperm in males prolactin (PRL) stimulates mammary glands to produce milk melanocyte-stimulating hormone (MSH) synthesis and dispersion of melanin pigment

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Anterior Pituitary Gland  Hypothalamic

control of anterior pituitary gland

secretion 

Neurons in the hypothalamus secrete releasing hormones and inhibiting hormones into blood capillaries at the base of the hypothalamus. 

Each hormone delivered by hypothalamohypophysial portal system regulates secretion or inhibition of a specific anterior pituitary hormone.

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Hypothalamic Hormones: Gondotropin RF

Corticotropin RF

Thyrotropin RF

Growth Hor RF

Prolactin RF

(CRF)

Pituitary Hormones: Follicle SH & Lutenizing Hor.

Adrenocorticoptropin Thyrotropin SH Growth Hormone Hormone (ACTH)

Prolactin

Target Gland or Structure:

Ovaries & Testes (androgens, estrogen)

Adrenal Gland

Thyroid Gland

(cortisol)

(thyroxine)

Cells of body

Bones, breasts & cells of body 27

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Anterior pituitary cells and hormones Cell type

Pituitary Product population

Target

Corticotroph

15-20%

Adrenal gland Adipocytes Melanocytes

Thyrotroph

3-5%

ACTH β-lipotropin MSH TSH

Gonadotroph

10-15%

LH, FSH

Gonads

Somatotroph

40-50%

GH

Lactotroph

10-15%

PRL

All tissues, liver Breasts gonads

Thyroid gland

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What do these anterior ?pituitary hormones do Growth Hormone: stimulates cells to grow and divide  increases amino acid transport rate and protein synthesis  increases fat metabolism Typically, GH is secreted during sleep. GH secretion increases when malnourished 

GH influences bone growth via somatomedin: GH in blood GH arrives in liver liver secretes somatomedin cartilage divides bones grow!

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Problems with GH

 Too

much GH in children leads to gigantism  Too much GH in adults leads to acromegaly  Too little GH in children leads to dwarfism

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Other Anterior Pituitary Hormone Functions ACTH: 

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works on the cortex of the adrenal gland, influencing the release of cortisol stress can increase CRH secretion which will increase ACTH secretion negative feedback when adrenal cortex hormones in blood decrease CRH secretion

LH & FSH: 

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LH in females and in males leads to sex hormone secretion FSH in females causes growth and development of egg cellcontaining follicles in the ovary, and causes estrogen secretion FSH in males stimulates sperm production both hormones are regulated by GnRH, which is not significant in concentration until puberty 31

More Anterior Pituitary Hormone Functions PRL: 

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In females, PRL promotes lactation PRL decreases LH secretion (note that too much PRL cause sterility) Controlled by both PRH and PIH

TSH: 

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works on thyroid gland to cause secretion of hormones works on thyroid gland to affect its growth (too much TSH leads to a goiter) negative feedback via thyroid hormones in blood stress or cold temperatures can change TSH secretion 32

Posterior Pituitary Gland  Pituitary

gland hangs by a stalk from the hypothalamus of the brain.  

anterior pituitary - appears glandular posterior pituitary - appears fibrous

 Neurons

produce antidiuretic hormone (ADH) and oxytocin. 

stored in, and released from, the posterior pituitary gland in response to neural stimulation from the hypothalamus 33

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Function of Posterior Pituitary Lobe Hormones ADH: 

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as an “antidiuretic,” ADH decreases urine formation by having kidneys conserve water also can contract smooth muscle cells, as found in blood vessels-this causes an increase in blood pressure ADH release triggered by osmoreceptors and inhibited by stretch receptors in blood vessels

OT: 

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In females, contracts the uterine wall smooth muscles In females, helps to eject milk when lactating

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Effects of ADH

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Major Pituitary Gland Hormones

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The Thyroid Gland Structure:

This bi-lobed gland contains many follicles. A follicle is a group of cells encircling a lumen. The lumen contains material called colloid (a glycoprotein) within it. As hormones are produced by the cells, the hormones are either released into the colloid or directly into the blood. There are also extra follicular hormone-secreting cells, called C cells. These are found between lumina.

Hormones Produced: 

Thyroxine (T4)

made in follicle

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Triiodotyronine (T3)

made in follicle

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Calcitonin

made by C cells

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Regulation of Thyroxine Secretion

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...About the Thyroid Hormones T3 and T4: 

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Function: metabolism regulation (break down carbohydrates and fats, synthesize proteins) Can only be made by follicular cells when iodides are available Somewhat hydrophobic and get carried by proteins in the blood. Controlled by anterior pituitary lobe TSH T3 more effective, T4 more abundant

Calcitonin: 

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Function: decrease blood calcium levels and blood phosphate levels (by helping them get deposited in bone, and by stimulating excretion of them by kidneys) Controlled by blood calcium levels

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Problems with the Thyroid Gland

Hyperthyroidism:  

high metabolic rate, hyperactivity, sensitivity to heat, protruding eyes Grave’s disease: when hyperthyroidism is due to an autoimmune problem.

Hypothyroidism:   

in the adult: low metabolic rate, sensitivity to cold, sluggishness in an infant: cretinism-- stunted growth, mental retardation, abnormal bone formation Hashimoto’s disease: when hypothyroidism is due to an autoimmune problem (autoantibodies attack and destroy follicular cells) 41

Thyroid and Parathyroid Glands  Parathyroid

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gland and calcium homeostasis

four small glands attached to the thyroid 

produces parathyroid hormone (PTH)  

one of the essential hormones for survival stimulates osteoclasts in bone to dissolve calcium phosphate crystals and release Ca++ into the blood

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Regulation of Blood Calcium Levels

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Adrenal Glands

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The Adrenal Medulla Acts very much like a part of the sympathetic nervous system (fight or flight) Secretes two amines:  norepinephrine (20%)  epinephrine (80%) Stimulated by preganglionic neurons directly, so controlled by the hypothalamus as if part of the autonomic nervous system, NOT by tropic hormones 45

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Adrenal Glands  Adrenal 

cortex

Hormones from adrenal cortex are collectively referred to as corticosteroids. 

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Cortisol maintains glucose homeostasis, and modulates some aspects of the immune response. Aldosterone stimulates the kidneys to reabsorb Na+ and secrete K+ into the urine.

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More about Adrenal Cortex Hormones Aldosterone:

Cortisol:

Considered a mineralocorticoid

Considered a glucocorticoid

Regulates “mineral electrolyte” levels in the blood (for example: Na+ and K+ ions) How is aldosterone controlled?  blood plasma ion concentrations affect its secretion directly (but not always strongly)  kidney secretes renin in response to altered electrolyte levels, which triggers angiotensin activation in the blood, which leads to aldosterone secretion  ACTH from the anterior pituitary can cause

Overall effect of cortisol:  Helps to keep blood glucose concentration within a normal range between meals Specific actions of cortisol:  increases amino acid concentration in the blood (by inhibiting protein synthesis in select tissues)  promotes use of fat for energy production in our bodies (rather than glucose)  stimulates the liver to synthesize glucose (not from carbohydrates, 47 but from amino acids and

The Pancreas  This

gland has both endocrine and exocrine functions… (exocrine is for digestion)  The endocrine portion of the gland contains three types of cells, each making a different hormone, arranged into groups called Islets of Langerhans   

alpha cells: secrete glucagon beta cells: secrete insulin delta cells: secrete SS (somatostatin)

 Note

that these pancreatic hormones are involved in blood glucose regulation, and problems with them can lead to diabetes. 48

Blood Glucose Regulation by the Pancreas Insulin: Glucagon: It works on the liver to It works on the liver to cause remove glucose from the the production of glucose blood via:  making glycogen via:  

glycogenolysis gluconeogenesis

It is regulated by blood glucose levels directly: 

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preventing gluconeogenesis increasing glucose transport into cells

secreted when blood glucose It is also regulated by blood glucose levels directly drops (before next meal)

Prevents hypoglycemia

Prevents hyperglycemia

Note: glucagon and insulin work in opposition, and their combined effects control blood glucose 49

Antagonistic Actions of Insulin and Glucagon

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Gonads & Hormones

LH & FSH

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Pineal Gland Secretes only one hormone: melatonin Involved in your circadian rhythm (your recognition of day and night times):  

melatonin secretion decreases in the day melatonin secretion increases at night

Melatonin is also involved in longer rhythms, like monthly and seasonal… and is thought to be involved in the female menstrual cycle and maybe in the onset of puberty 52