A&P: Endocrine Note Package

Coordination of Body Functions

• The nervous and endocrine systems collaborate to coordinate bodily functions.
• The nervous system uses nerve impulses and neurotransmitter release to act.
• The endocrine system uses hormones to regulate cell activity in distant areas.
• Hormones are mediator molecules released in one part of the body, but regulate the activity in different areas.
• Most hormones circulate in the bloodstream and act by binding to or in their target.
• Hormones are very effective, at very low concentrations.
• The response of the endocrine system is slower and lasts longer than the nervous system.

Hormone Functions

• Hormones help regulate chemical composition and internal environment volume (interstitial fluid).
• Hormones help regulate metabolism and energy balance.
• Hormones control smooth and cardiac muscle fiber contractions.
• Hormones help regulate glandular secretions and some immune activities.
• Hormones control growth and development.
• Hormones regulate the operation of reproductive systems, and establish circadian rhythms.

Comparing Nervous and Endocrine Systems

Gland Types

• Exocrine glands secrete their products into ducts that carry secretions into body cavities, organ lumens, or the body's surface, like sebaceous, mucous, and digestive glands.
• Endocrine glands secrete products (hormones) into the interstitial fluid surrounding secretory cells, diffusing into blood capillaries and carried to target cells, like the pituitary, thyroid, parathyroid, adrenal, and pineal glands.
• Some organs/tissues that aren't exclusively endocrine glands (hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart, adipose tissue, placenta) also secrete hormones.

Hormone Activity

• Hormones affect target cells by chemically binding to specific protein receptors.
• Only target cells have receptors for a specific hormone.
• Receptors are constantly synthesized and broken down, ranging from 2,000 to 100,000 receptors per target cell.
• Down-regulation happens when excess hormones are present so the number of receptors decrease, making the cell less sensitive, and receptors undergo endocytosis and are degraded.
• Up-regulation happens when hormone deficiency increases the number of receptors, making the target tissue more sensitive to the hormone.

Hormones: Circulating vs. Local

• Endocrine hormones are circulating hormones, passing from secretory cells to interstitial fluid then into the blood.
• Paracrine hormones are local hormones that act on neighboring cells.
• Autocrine hormones act on the same cell that secretes them.
• Local hormones inactivate quickly.
• Circulating hormones last longer and are inactivated by the liver and excreted by the kidneys.
• Nitric Oxide (NO), released by endothelial cells lining blood vessels, relaxes nearby smooth muscle fibers, causing vasodilation and exemplifies local hormones.

Lipid-Soluble Hormones

• Steroid hormones are derived from cholesterol, differing in attachment sites for chemical groups on the ring, like testosterone and estrogen.
• Thyroid hormones (T3 and T4) attach iodine to tyrosine which makes them lipid soluble.
• Nitric Oxide (NO) acts as both a hormone and neurotransmitter.
• Lipid-soluble hormones bind to transport proteins for blood transport, making them temporarily water-soluble, slowing their passage through the kidneys' filtration system, and providing a hormone reserve in the bloodstream.

Water-Soluble Hormones

• Amine hormones use amino acids as their base, retaining their amino group (NH3+), including epinephrine and norepinephrine.
• Peptide and protein hormones are amino acid polymers, classified as small or large, including oxytocin (peptide), insulin, and human growth hormone (protein).
• Eicosanoid hormones are derived from arachidonic acid (a 20-carbon fatty acid), including prostaglandins and leukotrienes.

Hormone Action

• The response to the hormone depends on the hormone and the target cell, including the synthesis of new molecules, changing permeability of the plasma membrane, stimulation of transport of a substance into or out of a cell, altering the rate of reactions, and causing contraction in smooth or cardiac muscle.
• Each target cell responds differently, for example in liver cells, insulin stimulates glycogen synthesis while in adipocytes, insulin stimulates triglyceride synthesis.
• Hormone response depends on hormone concentration, the number of hormone receptors, and influences by other hormones.
• The permissive effect requires simultaneous or recent exposure to the second hormone, enhancing the action of the first hormone.
  • Epinephrine weakly stimulates triglyceride breakdown, but with the presence of T3 or T4, epinephrine stimulates breakdown more powerfully.
• Synergistic effects happens when two hormones acting together have greater effects than each hormone acting alone.
  • Normal oocyte development requires both follicle-stimulating hormone and estrogens.
• Antagonistic effect happens when one hormone opposes the action of another hormone.
  • Insulin stimulates glycogen synthesis by liver cells but glucagon stimulates breakdown of glycogen in the liver.
• Lipid-soluble hormones and water-soluble hormones act differently.
• Lipid-soluble hormones must bind to their receptor within the target cell, while water-soluble hormones' receptors are part of the plasma membrane of the target cells.

Lipid-Soluble Hormone Mechanism

1. Free lipid-soluble hormone molecules diffuse from the blood, through interstitial fluid, and through the lipid bilayer into a cell.
2. The hormone binds to and activates receptors in the cytosol or nucleus. The activated receptor-hormone complex alters gene expression.
3. DNA is transcribed, mRNA forms, leaves the nucleus, and directs synthesis of a new protein on ribosomes.
4. New proteins alter cell activity, causing responses typical to that hormone.

Water-Soluble Hormone Mechanism

• Water-soluble hormones can't diffuse through the plasma bilayer so they bind to receptors on the cell's surface.
• Receptors are integral transmembrane proteins.
• Hormone binding to a receptor creates a 1st messenger, production of a 2nd messenger inside the cell, such as cAMP.

1. The water-soluble hormone diffuses from the blood through interstitial fluid and then binds to receptors on the surface of the target cell. The receptor-hormone complex activates a protein called G protein which in turn activates adenylate cyclase.
2. Adenylate cyclase converts ATP to cyclic AMP (cAMP).
3. cAMP activates one or more protein kinases, which are enzymes that phosphorylate other cellular proteins.
4. Activated protein kinases phosphorylate cellular proteins, activating some and inactivating others.
5. The phosphorylated proteins cause reactions that produce physiological responses.
6. After a period of time, phosphodiesterase acts to inactivate cAMP.

• Other 2nd messengers include calcium ions, cGMP, inositol triphosphate (IP3), and diacylglycerol (DAG).
• Hormones induce their effects at very low concentrations because they initiate a cascade; each step amplifies the initial effect.
  • A single hormone molecule binds to a receptor, activating 100 G-proteins, which activate 1000 cAMP, which then acts upon substrate molecules.
• Hormone secretion happens in short bursts; stimulated release occurs more frequently and increases hormone concentration in the blood. When there is no stimulation, hormone blood levels decrease.

Regulation of Secretion

• Hormone secretion is regulated by signals from the nervous system, chemical changes in the blood, and other hormones.
• Most hormones work via negative feedback, but a few use positive feedback.
  • Low blood glucose triggers glucagon release to stimulate glycogen breakdown, increasing blood glucose. Rising blood glucose stops glucagon release (negative feedback).
  • During childbirth, oxytocin is released, increasing uterine contractions; increased contractions stimulate further oxytocin release (positive feedback).

Hypothalamus & Pituitary

• The hypothalamus is a brain region below the thalamus, acting as a major link between the nervous and endocrine systems.
• The hypothalamus synthesizes at least 9 hormones, with the pituitary gland secreting 7.
• Together, these hormones regulate growth, development, metabolism, and homeostasis.
• The pituitary gland is a pea-shaped structure (1-1.5cm) in the hypophyseal fossa of the sella turcica of the sphenoid bone.
• It attaches to the hypothalamus via the infundibulum stalk.

Pituitary Sections

• There are two separate portions:
  • The anterior pituitary (adenohypophysis) is consisted of the pars distalis (larger portion) and pars tuberalis (forms a sheath around the infundibulum).
  • The posterior pituitary (neurohypophysis) is consisted of the pars nervosa (larger portion) and the infundibulum.

Hypophyseal Portal System

• Hypothalamic hormones use this system to reach the anterior pituitary.
• A portal system features blood flowing from one capillary network into a portal vein, then into a second capillary network without passing through the heart.
  • Blood flows from capillaries in the hypothalamus into portal veins to capillaries of the anterior pituitary.
• Superior hypophyseal arteries (branches of the internal carotid arteries) supply blood to the hypothalamus.
• At the hypothalamus-infundibulum junction, arteries divide into the primary plexus of the hypophyseal portal system.
• Blood then drains into hypophyseal portal veins passing down the infundibulum's outside.
• In the anterior pituitary, portal veins split again to form the secondary plexus of the hypophyseal portal system.

Neurosecretory Cells

• Located near the medial eminence and above the optic chiasm.
• Specialized neurons produce hypothalamic releasing and inhibiting hormones in their cell bodies.
• Hormones are packaged inside vesicles and reach terminals through axonal transport.
• Nerve impulses cause vesicles to undergo exocytosis.
• Hormones diffuse into the primary plexus of the hypophyseal portal system, moving to secondary plexus.
• This direct route allows hypothalamic hormones to act immediately.
• Hormones secreted by the anterior pituitary pass into the secondary plexus, which drains into anterior hypophyseal veins and the general circulation.

Anterior Pituitary Activity

• Releasing hormones stimulate the release of anterior pituitary hormones.
• Inhibiting hormones from the hypothalamus suppress it.
• There are 5 types of anterior pituitary cells.

Anterior Pituitary Cell Types

1. Somatotrophs secrete human growth hormone or somatotropin which stimulates tissue to secrete insulinlike growth factors to simulate growth and metabolism.
2. Thyrotrophs secrete thyroid-stimulating hormone (TSH) or thyrotropin to control thyroid gland secretion.
3. Gonadotrophs secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) which stimulates secretion of estrogens, progesterone, and the maturity of oocytes.
4. Lactotrophs secrete prolactin to initiate milk production in mammary glands.
5. Corticotrophs secrete adrenocorticotropic hormone (ACTH) or corticotropin to stimulate the adrenal cortex to secrete glucocorticoids like cortisol. Additionally, corticotrophs secrete melanocyte-stimulating hormone (MSH).

• Neurosecretory cells secrete 5 releasing hormones and 2 inhibiting hormones to regulate hormone secretion.
• Negative feedback happens when hormones released by target glands decrease the secretion of the three types of anterior pituitary cells and happens when their target gland hormones rise, impacting thyrotrophs, gonadotrophs, and corticotrophs.

Human Growth Hormone (hGH)

• The most plentiful anterior pituitary hormone.
• Promoting synthesis and secretion of insulinlike growth factors (IGFs) which enter the bloodstream or act locally in other tissues.
• IGFs cause cell growth and multiplication by increasing amino acid uptake and accelerating protein synthesis.
• IGFs decreases protein breakdown and amino acid use for ATP production.
• The released fatty acids increase lipolysis in adipose tissue to be used for ATP production.
• IGFs decreases glucose uptake to ensure it is available to neurons for ATP production.
• Somatotrophs release hGH every few hours, especially during sleep.
• Secretion is controlled by growth hormone-releasing hormone (GHRH) and growth hormone-inhibiting hormone (GHIH).
• HYPOGLYCEMIA happens when low blood glucose stimulates the hypothalamus to release GHRH, stimulating somatotrophs to release hGH.
• HYPOGLYCEMIA: hGH stimulates insulinlike growth factor secretion (breakdown of liver glycogen) to cause glucose to enter the blood faster.
• The blood glucose rises and inhibits GHRH release.
• HYPERGLYCEMIA happens when high blood glucose stimulates the hypothalamus to secrete GHIH, which travels to the anterior pituitary to inhibit hGH secretion.
• Low levels of hGH slows glycogen breakdown in the liver.
• The blood glucose falls and inhibits GHIH release.
• Other stimuli that promotes hGH: decreased fatty acids, increased amino acids in blood, deep sleep, increased SNS activity.

Thyroid-Stimulating Hormone (TSH)

• Thyrotrophs produce TSH.
• TSH stimulates the synthesis and secretion of T3 and T4, both produced by the thyroid gland.
• Thyrotropin-releasing hormone (TRH) from the hypothalamus controls TSH secretion.
• It has no inhibitory hormone.

Follicle-Stimulating Hormone (FSH)

• Gonadotrophs produce FSH, targeting the ovaries.
• Each month, FSH initiates the development of secondary ovarian follicles and stimulates follicular cells to secrete estrogens.
• in men, FSH stimulates sperm production in the testes.
• Gonadotropin-releasing hormone (GnRH) stimulates FSH release.
• Negative feedback systems use estrogen in females and testosterone in males.

Luteinizing Hormone (LH)

• Gonadotrophs produce LH.
• LH triggers ovulation (the release of a secondary oocyte) by an ovary and stimulates the formation of the corpus luteum in the ovary and the secretion of progesterone by corpus luteum.
• Together, FSH and LH stimulate secretion of estrogen.
• Estrogen and progesterone prepare the uterus for implantation of fertilized ovum.
• LH stimulates cells in testes to secrete testosterone.
• Controlled by GnRH.

Prolactin

• Lactotrophs produce prolactin.
• Prolactin initiates and maintains milk secretion by the mammary glands.
• The action of estrogen, progesterone, glucocorticoids, hGH, thyroxine, and insulin are needed to bring about milk secretion.
• The hypothalamus secretes both inhibitory and excitatory hormones that regulate prolactin secretion.
• Prolactin-inhibiting hormone (PIH) = dopamine, inhibits the release of prolactin most of the time.
• PIH decreases just before menstruation begins each month, and blood levels of prolactin rise (this is cause of breast tenderness before menstruation).
• Prolactin releasing hormone (PRH) causes a rise in prolactin levels during pregnancy.
• Function unknown in men.

Adrenocorticotropic Hormone (ACTH)

• Corticotrophs produce ACTH.
• ACTH controls cortisol and other glucocorticoid production/secretion by the adrenal glands' cortex (outer portion).
• It is regulated by corticotropin-releasing hormone (CRH).

Melanocyte-Stimulating Hormone (MSH)

• Corticotrophs produce MSH.
• The function is unknown in humans but increases skin pigmentation in amphibians and may influence brain activity.

Posterior Pituitary

• Posterior pituitary hormone production and hormone storage does not occur here; rather it stores and releases 2 hormones made in the hypothalamus.
• Cell bodies of neurosecretory cells are in paraventricular and supraoptic nuclei of the hypothalamus.
• Axons form the hypothalamohypophyseal tract from the hypothalamus to blood capillaries in the posterior pituitary.
• The paraventricular nucleus synthesizes oxytocin.
• the supraoptic nucleus produces antidiuretic hormone (ADH) or vasopressin.
• Hormones move by fast axonal transport to neuron terminals in the posterior pituitary.
• Blood supply is from inferior hypophyseal arteries which drain into the capillary plexus of the infundibular process, then into posterior hypophyseal veins.

Oxytocin

• Enhances contraction of smooth muscle cells in the uterine wall and stimulates milk ejection from mammary glands in response to the suckling infant.
• Function in men and nonpregnant women is unclear.

Antidiuretic Hormone (ADH)

• Also called vasopressin.
• Acts to decrease urine production.
• Stimulates water reabsorption by the kidneys and arteriolar constriction, causing the kidneys to return more water to the blood.
• In the absence of ADH, urine output increases more than tenfold.
• Alcohol inhibits the secretion of ADH.
• ADH decreases water lost through sweating and constricts arterioles, increasing blood pressure.

ADH Regulation

1. High blood osmotic pressure (low blood pressure) stimulates osmoreceptors (neurons in the hypothalamus that monitor blood osmotic pressure).
2. Osmoreceptors activate hypothalamic neurosecretory cells to synthesize and release ADH.
3. This generates nerve impulses, causing exocytosis of ADH vesicles into the posterior pituitary, liberating ADH, which diffuses into blood capillaries.
4. Blood carries ADH to the kidneys, sweat glands, and smooth muscle in blood vessel walls. Kidneys retain more water, sweat gland activity decreases, and arterioles constrict, increasing blood pressure.
5. low osmotic pressure of blood (higher blood volume) inhibits osmoreceptors.
6. Inhibition of osmoreceptors reduces ADH secretion. Kidneys retain less water, sweat gland activity increases, and arterioles dilate. Pressure/blood volume returns to normal.

Thyroid Gland

• The butterfly-shaped thyroid gland is located inferior to the larynx.
• It has a right and left lobe connected by an isthmus.
• Spherical sacs called thyroid follicles make up most of the gland.
  • Each follicle's wall consists of follicular cells, extending to the lumen (internal space) of the follicle.
  • The basement membrane surrounds each follicle.
• Follicular cells range from low cuboidal/squamous in shape when inactive to cuboidal to columnar when active.
• Follicular cells produce thyroxine (T4) and triiodothyronine (T3), both thyroid hormones.
• Some cells called parafollicular cells (C cells) produces calcitonin.

Thyroid Hormone Formation

• The thyroid gland stores its secretory products in large quantities.
• Thyroid hormones are synthesized from iodine and tyrosine in thyroglobulin (TG).
• Hormones are transported in the blood by plasma proteins, including thyroxine-binding globulins (TBG).

Thyroid Hormone Creation Rundown

1. Iodide trapping: Follicular cells trap iodide ions (I-) via active transport from the blood into the cytosol.
2. Synthesis of thyroglobulin: Follicular cells synthesize thyroglobulin (TGB), a glycoprotein produced in the rough ER.
3. Oxidation of iodide: Tyrosines become iodinated and iodide ions are oxidized to iodine (2I- -> 2 I2).
4. Iodination of tyrosine: Iodine molecules react with tyrosines to form either T1 or T2. This creates a sticky material called colloid.
5. Coupling of T1 and T2: Either two T2 molecules combine to make T4 or a T2 and a T1 molecule to form T3
6. Pinocytosis and digestion of colloid: Droplets of colloid reenter follicular cells and merges with lysosomes.

Thyroid Hormone Release

• T3 and T4 are lipid-soluble and diffuse through the plasma membrane into interstitial fluid and blood.
• More T4 than T3 circulates, but T3 is more potent.
• most T4 is converted to T3 once it enters a body cell.
• Over 99% combines with transport proteins in the blood, typically thyroxine-binding globulin (TBG).

Thyroid Hormone Secretion

• remember thyrotropin-releasing hormone (TRH) from hypothalamus and thyroid-stimulating hormone (TSH) from anterior pituitary.
• T3 & T4 synthesize/release.

1. Low blood levels of T3 and T4, or low metabolic rate, stimulates the hypothalamus to secrete TRH.
2. TRH flows to the anterior pituitary and stimulates thyrotrophs to secrete TSH.
3. TSH stimulates cell activity (iodine trapping, and growth of follicular cells).
4. Follicular cells release T3 and T4 into the blood until the metabolic rate normalizes.
5. Elevated T3 inhibits the release of TRH and TSH (negative feedback).

Functions of Thyroid Hormones

1. Increased BMR, rate of oxygen consumption by stimulating use of cellular oxygen to produce ATP.
2. Stimulates the synthesis of more sodium-potassium pumps (Na-K ATPase) increasing ATP use.
3. Stimulates synthesis of protein, increased use of glucose and fatty acids, and enhances cholesterol excretion.
4. Enhances of catecholamines.
5. Works with human growth hormone and insulin.

• Hyperthyroidism symptoms: increased heart rate, forceful heartbeats, and blood pressure. Other increasing factors: cold, hypoglycemia, high altitude, pregnancy.

Calcitonin's Role

• Parafollicular cells in thyroid gland produces this hormone.
• Calcitonin can decrease calcium in the blood.
• It is done by Inhibit osteoclast which leads to bone extracellular matrix breakdown.
• It is also done by accelerating uptake of calcium and phosphates into bone extracellular matrix.
• Miacalcin: extract is from salmon. It can prescribed 10x because it is more potent.
• Also used to treat osteoporosis

Parathyroid Glands

• Embedded in the posterior of the thyroid gland
• attached one superior and one inferior set
• Consist of two epithelial cells: - numerous (PTH or principal) produces PTH - Oxyphil: function remains unkown

PT H

• Major regulator (magnesium, calcium, and ions)

1. increase activity and number in osteoclast
2. PTH affects kidneys:
   • less loss with with calcium and magnesium
   • calcium is increased PTH is increased.

Adrenal Glands

• Two paired kidneys located superior.
• Has cortex which is outer and medulla.
• Medulla are responsible to three hormones (norepinephrine/epinephrine is dopamine)

Adrenal Cortex

• Divided into 3 different parts:
• secretes MIN which capsule
• Z.F is widest with long columns

Mineralcorticoids

• major hormone regulates K+ ions.
• Helps with volume (blood)
• Secretes aldosterone

RAA

1. stimulus to start includes decrease/dehydration
2. volume blood decreases

Functions of ATII

• vasoconstriction with muscle contractions of walls

4. Blood increases

Gluco

• Includes the stress factors
• cortisol is hormone in zona facis.
• controls by CRH

Effects of Gs

• increase liberation in amino acids:
• glucose can be used

Androgen

• Reticularis secretes weak hormones
• testosterone after puberty

Medulla

1. ganglia autonomic modified
2. hormones is secreted 4, ANS has direct influence
3. increases heart rate and blood flow. and fats increase

Pancreas

• Has exocrine
• Is located and consists tail, body and head.

Regulations

• glucogon levels high
• acts more
• Hypogl
• glucose increases
• high glucose levels stimulates insulin with beta cells

Testicles and Ovarines

• hormones
• estro and tester
• Test stim
• FSH is testes.

Pineal

• melato is produced

EIsnsads

• in chem stimulation.

Inflammtion

• reprodcutve secretio
• transmite impulse.

GF

• increase growht.

GAS

Exhaustion

• causes decrease. can result in failure.

Disorder

• pituitary failure
• slows growth.
• can lead is acromegaly is excess HGH
• Diabetes: cannot reproduce. results volume large and increase thirst.

Disorders

Auto

• cortex is damaged/failure.
• lethargy vomiting occurs.

Tumor

• causes heart increase rates
• Islets will fail to work.
• Hyper too much from diabetes.

Type 1 DM

• Needs injection. Has fatty acids

Type 2 DM

• cells are reduce or sensitize.
• Hyperinsulim: increase glucose uptake. trem tremor happn and increase heart rate.
• This chapter shows the interrelations hormones and the importance.