Human Physiology Endocrine Review Guide(SARC – Beau M.)

-Chapter 15: The Endocrine System -The endocrine system and nervous system are the major information centers between different cells and tissues of the body. -Hypothalamus: “President” of the Endocrine System >inferior region contains the Pituitary Gland-Pituitary Gland: “Vice President” of the Endocrine System >has 3 lobes: Anterior, Intermediate, Posterior-Peripheral glands: “citizens”, includes the Adrenal Gland, Thyroid Gland, Ovaries, Testes

-Mechanisms of Hormone Secretion-Endocrine Hormones: a chemical substance which is produced and secreted by the cells of an Endocrine gland and released into blood circulation, which carries it to its target cells. Endocrine hormones all require specific receptors on their target cells, without receptors they cannot bind to the target cell, and the cell will not carry out the physiological action that the hormone is signaling for (stimulation or inhibition).

Exocrine Hormone: a chemical substance produced in exocrine cells that is NOT secreted into the circulatory system but instead secreted into interstitial fluid, the surface of tissue, or into a cavity. This includes: -Pancreatic enzymes secreted by: Pancreas -Saliva secreted by: Salivary glands (Sublingual, Submandibular, Parotid) -Sweat secreted by: Sweat glands-Exocrine hormones are produced in the Acinus and secreted out of the gland by ducts (Pancreatic duct, Common Bile duct, Parotid duct, etc.), which open into the cavity/surface of the target organ/tissue. >Paracrine Hormones: stimulate/inhibit the actions of neighboring target cells. Target cells may or may not be hormone-producing. For example: Somatostatin inhibits Insulin secretion in Pancreatic β-cells. >Autocrine Hormones: give feedback to their own cell to stimulate/inhibit cellular activity. They bind to their own receptors on their own cell surface. >Intracrine Hormones: stimulate/inhibit cellular activity inside their own cell without being secreted. For example: Insulin can inhibit its own secretion from pancreatic β-cells.

-Hormone Synthesis-Protein hormones: Are produced the same way as other cellular protein products. Includes GH, Prolactin, and PTH.Peptide hormones: Are produced from cleaving off a portion from larger protein precursors. Includes Insulin, ACTH, and Glucagon. Thyroid hormones: Are produced by “Organification”, the combination of Iodine and Tyrosine (residues of Thyroglobulin proteins), and the “Coupling” of the different molecules produced by those combinations.Steroid hormones: Are produced from a cholesterol precursor molecule.

-Protein Hormones vs Steroid Hormones-Binding Site:

-Protein hormones bind to: cell-surface receptors -Steroid hormones bind to: Nuclear (intracellular) receptors

Lipophobic vs Lipophilic: -Protein hormones: are Lipophobic (lipid repulsed) -Steroid hormones: are Lipophilic (lipid-loving)

Hydrophobic vs Hydrophilic: -Protein hormones: are Hydrophilic (water loving) -Steroid hormones: are Hydrophobic (water repulsed)

Requires a Carrier/Transport molecule in the blood: -Protein hormones: DO NOT require a carrier, can circulate freely in the blood -Steroid hormones: DO require specific carriers to move through blood to reach their target cell -Thyroid hormones: DO require carriers

Duration of the hormone action on their target cell: -Protein hormones: Short because they have no transporter/carrier -Steroid hormones: Long because they must dissociate from their transporter/carrier before binding

Precursor: -Protein hormones: amino acid precursor (and peptide hormones) -Steroid hormones: cholesterol precursor -Thyroid hormones: iodide (I-) precursor and amino acid: _____ Tyrosine _________

-Hormone Receptors- -Cell surface receptors -are located on target cell membrane surface -bind protein and peptide hormones -ex: Insulin, Growth Hormone, and Prolactin

-Nuclear receptors (intracellular receptor) -are located inside the target cell at the nucleus -bind steroid and thyroid hormones -ex: Testosterone, Androgen, Estrogen, Progesterone, Aldosterone, Cortisol, T3, T4, and vitamin D

-Hormone Effects-Synergistic Effects: When two or more different hormones have similar functions and effects on their target cell, and work in harmony for a specific outcome. For example: Aldosterone and Norepinephrine both increase blood pressure, and Cortisol and Insulin both regulate blood glucose.

Permissive Effects: When one hormone gives “permission” for the action of a second hormone. It can also enhance the responsiveness of a target cell to the second hormone, or it can increase the activity of the

second hormone. Antagonistic Effects: When the binding of one hormone inhibits the effects of another. This effect is typically used when designing drugs like synthetic hormones, so they can recognize and bind to natural hormone receptors to block natural hormones from binding there (inhibits a process that may have become pathological). For example: Propranolol is an antagonist for β1 receptors by binding and blocking Norepinephrine from being able to bind.Agonists: act like natural hormones and bind to natural hormone receptors. For example: in Hormone Replacement Therapy, Growth Hormone (GH) receptors are bound by synthetic Growth Hormones to treat growth conditions like Dwarfism.

-Steroid and Thyroid hormone mechanisms-Step 1 – Steroid or Thyroid hormones diffuse across the target cell membraneStep 2 – hormone binds to the cytoplasmic site on its Nuclear receptor proteinStep 3 – Nuclear receptor undergoes conformational changes to expose DNA-binding site of the target geneStep 4 – The target gene is transcribed, resulting in an mRNA sequence of that target geneStep 5 – The new mRNA sequence is translated to produce a specific protein product that will satisfy the cellular physiological reaction to the binding of the initial hormone signal

-HYPOTHALAMUS SECRETIONS AND FUNTIONS--The Hypothalamus controls many things including body temperature, sleep, memory, learning, emotional and sexual behavior (associated with the Limbic System), Autonomic Nervous System, and Endocrine System.

1 – CRH (Corticotropin Releasing Hormone): The blood vessel connecting the Hypothalamus and Anterior Pituitary, HPPS (Hypothalamic Pituitary Portal System), releases Releasing Hormone (RH) from Hypothalamic nuclei into the Anterior Pituitary, which contains Trophic cells. CRH is released from Hypothalamus into the HPPS vessel and carried into the Anterior Pituitary, where there are Corticotropic cells. CRH binds to these cells to stimulate the secretion of ACTH (Adrenocorticotropic Hormone), which is then carried by the blood to the Adrenal Cortex (of the Adrenal Gland) in order to bind to Adrenal Cortex cell-surface receptors to stimulate secretion of zone-specific hormones.

2 – TRH (Thyrotropin Releasing Hormone): Released through HPPS and binds to surface receptors on Thyrotropic cells in the Anterior Pituitary in order to stimulate the cells to secrete TSH (Thyroid Stimulating Hormone), which enters the blood to stimulate the Thyroid Gland to secrete T3 and T4 hormones. TRH (for Dr. Flory its PRH) can also stimulate the Anterior Pituitary to secrete Prolactin.

3 – GnRH (Gonadotropin Releasing Hormone): stimulates Gonadotropic cells in the Anterior Pituitary to secrete FSH (Follicle Stimulating Hormone) and LH (Luteinizing Hormone).

4 – GHRH (Growth Hormone Releasing Hormone): secreted by Hypothalamus into Anterior Pituitary to bind to receptors on Somatotropic cells to stimulate the secretion of GH (Growth Hormone). GH is also secreted by the Placenta in pregnant females.

-Anterior Pituitary Hormones- 1 – TSH (Thyroid Stimulating Hormone) & PL (Prolactin): TRH is secreted by Hypothalamus through HPPS

vessels into the Anterior Pituitary and binds to Thyrotropic cell receptor to stimulate the cell to secrete TSH & Prolactin:

>TSH: binds to the surface of follicular cells in the Thyroid Gland (to a GPCR Receptor) and uses cAMP as a secondary messenger. Helps control the development of fetal Thyroid Glands (along with the T3 and T4 it stimulates) and helps with the development of the Central Nervous System (including Brain), and bones. >Prolactin (PL) (for Dr. Flory it’s stimulated by PRH): -in females: develops mammary glands for breastfeeding when pregnant, excess PL can cause infertility because it suppresses other sex hormones such as FSH and LH to inhibit menstruation and ovulation BUT during pregnancy Prolactin this is necessary to avoid spontaneous miscarriage of the fetus. -in males: PL helps control emotional and sexual behavior, but excess can cause infertility because it suppresses other sex hormones -Dopamine inhibits release of Prolactin -Hyperprolactinemia is treated with synthetic Dopamine (Bromocriptine)2 – ACTH (Adrenocorticotropic Hormone): Hypothalamic CRH stimulates Corticotropic cells to secrete ACTH from the Anterior Pituitary lobe. -ACTH enters the blood to stimulate cells in the Adrenal Cortex, which leads to secretion of: Cortisol, Aldosterone, & Androgen 3 – GH (Growth Hormone): Hypothalamic GHRH stimulates Somatotropic cells to secrete Growth Hormone (GH) from the Anterior lobe of the Pituitary gland. GH is also secreted by the Placenta in pregnant females. -Effect of GH (growth hormone): GH stimulates cell proliferation (increase in cell number) and cell growth in child and in fetus (active during embryogenesis, and development of brain, heart, blood vessels, soft tissue). -GH levels increase in pregnancy & in childhood -GH levels decrease after puberty -GH excess during childhood may cause Gigantism, where the child grows extremely tall, and have an enlarged heart. This is usually treated preventatively with synthetic Somatostatin. -excess GH secretion after puberty or in adults causes Acromegaly (enlarged face, hands, and feet) -GH deficiency can lead to Dwarfism, which is treated with Synthetic Growth Hormone.

4 – FSH (Follicle Stimulating Hormone) & LH (Luteinizing Hormone): Hypothalamic GnRH stimulates Gonadotropic cells to secrete Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH):

-Effect of FSH & LH in females: Receptors in the ovaries. Controls development of follicle and ovum during first two weeks of menstrual cycle (Follicular Phase), when FSH level increases to control maturation and development of a follicle. By the Midcycle (day 13, 14, or 15) FSH level decreases & LH level increases for the beginning of Ovulation. LH takes over last steps of maturation of follicle after FSH. LH causes the rupture of follicle cell, elimination of ovum from follicle, and the migration of ovum toward fallopian tube. After ovulation, if there is no sperm there is no pregnancy.

-Effect of FSH & LH in males: FSH has receptors in the testes, and controls development of sperm from germ cells. LH has receptors in the testicle on Leydig cells, where it stimulates Testosterone secretion. Testosterone is important for the development of testicles in male fetus, development of external genitalia in

fetus and child, and in the descent of testes from the abdominal cavity to the scrotum in the fetus. >Testosterone controls secondary sex characteristics: muscles, voice, libido >Testosterone: Controls body temp, increases red blood cell production, controls mood, sleep, appetite, body metabolism >Testosterone deficiency in the fetus leads a failure of testicular descent

-Posterior Pituitary Hormones--The cell bodies of two nuclei, the Supraoptic and Paraventricular nuclei are contained in the Hypothalamus, but their axons project into the Posterior Pituitary lobe. When stimulated, they produce and secrete 2 hormones from their axon terminals: >ADH (Antidiuretic Hormone): (also called Vasopressin) osmoreceptors in large blood vessels are sensitive to blood osmolarity and are stimulated when blood becomes too concentrated (possible dehydration). These osmoreceptors are under the control of two cranial nerves: CN X (Vagus) and CN IX (Glossopharyngeal) and they carry information about blood osmolarity to two Hypothalamic nuclei: Supraoptic nuclei and Paraventricular nuclei, which stimulates them to secrete ADH into the Posterior Pituitary when the blood volume is low (dehydrated). ADH is released into the blood and carried to the Renal System, where it binds to the Vasopressin-2 (V2) surface receptor on the Collecting Tubule of the Nephrons. This stimulates reabsorption of H2O into the Peritubular capillaries to decrease osmotic pressure in the tubules and increase blood volume by diluting the blood. This decreases urination and relieves dehydration. >Oxytocin: -in females: is important for lactation in mammary glands, and in the uterus it has receptors on the myometrial cells of the uterus smooth muscle layer (Myometrium) to control contractions during labor and childbirth. -in males: is important in the control of ejaculation and vasoconstriction

-Adrenal gland (Cortex)--Adrenal glands (Suprarenal glands) are located on the upper pole of each kidney. -Each gland is 90% outer layer (Adrenal Cortex) and 10% inner layer (Adrenal Medulla). -Adrenal Cortex secretion is regulated by ACTH from the Anterior Pituitary-The Adrenal Cortex has 3 layers: Zona Glomerulosa, Zona Fasciculata, & Zona Reticulata >Androgen: sex hormone seen in males and females (important in females to begin puberty) -sex hormone produced in the Zona Reticulata of the Adrenal Cortex -binds to a Nuclear receptor -crucial hormone in puberty, involved in Axillary and Pubic hair growth, and acne >Aldosterone: increase NaCl and H2O reabsorption in Nephron, increases blood pressure & volume -is a “mineralocorticoid” produced in the Zona Glomerulosa of the Adrenal Cortex -binds to a Nuclear receptor in cells of the Collecting Tubule of Nephron -involved in the Renin-Angiotensin System (see below) -Increases NaCl, H2O, and HCO3

- reabsorption, increases blood pressure -Increases excretion of H+ and K+ into urine -Activated when blood pressure is low

>Cortisol: “stress hormone”, maintains blood glucose, metabolism and appetite -is a “glucocorticoid” produced in the Zona Fasciculata of the Adrenal Cortex -binds to a Nuclear receptor on target cells -increases metabolic break down of proteins (Proteolysis) and lipids (Lipolysis) -suppresses immune system and inflammation -Stimulates gluconeogenesis and

-More on Aldosterone: >Renin-Angiotensin-Aldosterone System: activates when blood pressure, blood volume or Na+ level is low → stimulates Renin secretion → Renin converts Angiotensinogen (Ag) into Angiotensin-1 (Ag1) → Then ACE (Angiotensin Converting Enzyme) secreted from the lungs converts Ag1 into Ag2 (Angiotensin 2) → Ag2 acts as a vasoconstrictor and stimulates the production of Aldosterone from Corticosterone in the Zona Glomerulosa of the Adrenal Cortex → Aldosterone is carried by the blood to the Nephron and binds to its receptor on the Collecting Duct and Late Distal Tubule → stimulates Peritubular capillaries to reabsorb NaCl and H2O, absorb HCO3

-, and excrete K+ and H+ into the urine. In this way Aldosterone increases blood pressure & volume and Na+ blood concentration.-Excessive amounts of K+ in the blood (Hyperkalemia) increase Aldosterone secretion, and Aldosterone then increases K+ secretion into the urine to regulate its level in the blood.

-Adrenal gland (Medulla)--Secretes Catecholamines: Adrenaline/Epinephrine and Noradrenaline/Norepinephrine -Adrenal Medulla is NOT under the control of the Pituitary gland or Hypothalamus. (Neither are Pancreas or Parathyroid) -The Adrenal Medulla is derived from embryonic Ectoderm tissue (which is neural and gives rise to the CNS and PNS as well)-Noradrenaline & Adrenaline have receptors in the Liver for controlling Gluconeogenesis and Glycogenesis.

-Norepinephrine: is produced by Chromaffin cells in the Adrenal Medulla, CNS, and in Peripheral Sympathetic nerves. These hormones also act as neurotransmitters. It controls smooth muscles (including the smooth muscles layer around blood vessels and the viscera lining of organs) in the GI, Respiratory System, Sweat glands, and Heart. Heart activity, heart rate, conduction velocity, and contractility are all influenced by Norepineprine as well. -Effects of Norepinephrine depend on the type of receptor it binds to: >α1: vasoconstriction, contraction of smooth muscles (including sphincters), blood pressure increases >α2: relaxation of smooth muscle, dilation of sphincter, vasodilation >β1: increased heart rate, myocardial contractions, and conduction velocity. Propranolol and Atenolol are Antagonists (β-blockers). >β2: Relaxes bronchi. Albuterol is an Agonist for Norepinephrine at this receptor

-Epinephrine: is produced by Chromaffin cells in the Adrenal Medulla. Controls blood pressure, Controls glucose formation and absorption in liver

-Adrenaline and Noradrenaline Synthesis:-Precursor amino acid Tyrosine is catalyzed by the enzyme Tyrosine Hydroxylase to become Dihydroxyphenylalanine (DOPA), which is catalyzed by the enzyme DOPA-decarboxylase to become Dopamine, which is catalyzed by enzyme Dopamine-β-hydroxylase to become Norepinephrine, which can be catalyzed by enzyme Phenylethanolamine-N-methyltransferase to become Epinephrine

-Thyroid gland--The located alongside the Hyoid bone and the 1st ring of the Trachea in the throat. -Has 2 lobes (Left & Right). -The blood supply to the Thyroid gland is important and brings Iodide (I-), a precursor for hormones (T3 & T4). -Blood from the Inferior Thyroid Artery (a branch of the Thyrocervical trunk, which comes from the Subclavian artery) supplies the Inferior lobe of the Thyroid gland. -Blood from the Superior Thyroid Artery (a branch of the External Carotid artery, which comes from the Common Carotid artery) supplies the Superior lobe of the Thyroid gland. -Venous blood drains from the Thyroid gland into the Inferior & Superior Thyroid veins → to the Internal Jugular vein in the neck → to the Brachiocephalic vein → then into the Superior Vena Cava. -Thyroid nerve supply is controlled by the Autonomic Nervous System (Parasympathetic & Sympathetic).-The Thyroid gland derives from embryonic Endoderm tissue. -Internal Structure: The Thyroid gland has a single layer of follicular cells, which have receptors for TSH on the basolateral surface of the cells, which faces the bloodstream. Inside the follicular lumen is “colloid” fluid which contains Thyroglobulin proteins (containing Tyrosine amino acids) which act as a precursor for T3 and T4 production.

-Thyroid Hormones--The thyroid gland produces two hormones: Thyroxine (T4) and Triiodothyronine (T3)-In the circulatory system, ~99.9% of all T4 and ~99.5% of all T3 in the blood are bound to plasma carrier proteins, most commonly Thyroxine Binding Globulin (TBG), to inhibit Renal excretion into the urine.-When TSH binds receptors on the basolateral-surface of follicular cells it activates the apical surface of the cell to reabsorb Thyroglobulin and Iodide to begin synthesis of Thyroid Hormones T3 and T4.-T3 and T4 bind to Nuclear receptors in their target cells and are critical in cell differentiation during development, and help in maintaining thermoregulation and metabolic homeostasis in the body.

-Synthesis of Thyroid Hormones-1 – Na+/I- symport pump transports iodide into follicle cells:-After TSH binds to its receptor on the follicle cell membrane, it activates the cells to uptake Thyroglobulin and iodide, which symports into the cell along with sodium. 2 – Iodide Oxidation: Iodide (I-) is catalyzed by Peroxidase enzyme to oxidize into iodine (I 2 ) , which is now reactive and ready to form the inactive forms of T3 and T4 by the process of “Organification”.

3 – Organification combines Iodine molecules with Tyrosine residues from Thyroglobulin:-when 1 molecule of Iodine (I2) and 1 molecule of Tyrosine combine, they form Monoiodotyrosine (MIT). -when 2 molecules of Iodine (I2) and 1 molecule of Tyrosine combine, they form Diiodotyrosine (DIT).

4 – Coupling makes combinations of MIT and DIT to form T3 and T4:-While MIT and DIT are attached to the Tyrosine residues of Thyroglobulin, two coupling reactions occur:

> 1 MIT + 1 DIT = T3 > 1 DIT + 1 DIT = T4-These reactions are catalyzed by Peroxidase enzyme, and result in the active forms of thyroid hormones.-More T4 than T3 is synthesized in this process, although T3 is more potent and active in bodily mechanisms.-T4 can be modified into T3 at the site of target tissue.

-Thyroid Hormone Physiological function: -T3 and T4 are both active independent of each other but can collaborate in function.-T4 can pass through Placenta membrane and converts to T3 to control the development of the CNS, bone, and Thyroid gland in the fetus. >More specifically, T3 is synergistic with GH and Somatomedin hormones for fetal bone formation-In adults, Thyroid hormones control memory, learning, body metabolism and temperature, increases O2 consumption in different cells (except in the Brain, Spleen, and gonads), increases glucose absorption from the GI, controls glucose metabolism, gluconeogenesis & glycogenolysis in the Liver, increases Lipolysis and Proteolysis, increases sensitivity in α1 and β1 sympathetic receptors, increase ventilation rate, control heart rate, contractility of myocardium, and blood pressure.

-Parathyroid glands--Glands consist of 4 pea-sized lobes located posterior to the Thyroid Gland-They are sensitive to Phosphorus and Ca2+ levels in the blood (10 mg/dL is the normal Ca2+ value)-Chief cells secrete Parathyroid Hormone (PTH), which regulates blood levels of Ca2+ and Phosphorus >If PTH increases one the other will decrease-PTH secretion is controlled by a negative feedback loop, high levels of Ca2+ will decrease PTH secretion-PTH binds to receptors on bone (bone resorption) to remove Phosphate and Ca2+ from the bone and release it into the Extracellular fluid. This does not directly translate to increased serum levels of Ca2+ because the Phosphate will associate with Ca2+. By inhibiting Phosphate reabsorption in the Proximal Tubule of the Nephrons in the Renal System, Phosphates can be excreted into the urine in larger amounts (Phosphaturia), causing Phosphate to dissociate from Ca2+ to replace what was lost, then Ca2+ can enter blood serum to increase Ca2+ levels. -PTH receptors on the Distal Tubule of Nephrons results in Ca2+ reabsorption directly to the blood.-PTH also has receptors on the Epithelial cells of the small intestine and binds to increase Ca2+ absorption from Chyme in the small intestine.-Slight decreases in Mg2+ increase PTH secretion, but deficiencies in Mg2+ inhibit PTH secretion, which can lead to Hypoparathyroidism and Hypocalcemia.-PTH has receptors in the Distal Tubule of Nephron and binds to convert the inactive form of vitamin D (25-hydrocholecalciferol) into its active form (1,25-dihydroxycholecalciferol), which is then absorbed into the Peritubular capillaries. This process can generate cAMP for intracellular energy, which is then expelled as waste into the urine.-The vitamin D then travels to the GI to assist with Ca2+ absorption from epithelial cells in the small intestine.-Deficiency of PTH causes a deficiency of vitamin D, which causes a deficiency of Ca2+ and Osteoporosis.

-Hyperparathyroidism also causes Osteoporosis since excess PTH removes too much Ca2+ from the bones, weakening them.

-The Importance of Calcium in the Body--Calcium is important for muscular contractions and is seen in large amounts in the mechanism of the Neuromuscular Junction.-Calcium is used in large amounts in Cardiac Muscle to regulate contractility of myocardium, and in contractions of the smooth muscle layer of blood vessels, muscularis mucosa of the GI tract, and smooth muscle layers of internal organs.-Calcium regulates action potentials of SA (Sinoatrial) and AV (Atrioventricular) node in the right atrium of the Heart, and we see in Hypercalcemia, that excess Ca2+ increases heart rate by stimulating the SA and AV nodes-Calcium (and vitamin D) are important for maintaining bone density and development.

-Pancreas--The Pancreas is located between the second part of the Duodenum and the Spleen. It has both Exocrine and Endocrine function.-The Exocrine portion of the Pancreas has acini (acinar cells) which secrete digestive enzymes: >Lipases, Amylases, Proteases-The Endocrine portion of the Pancreas, called the islet of Langerhans contains 4 major cell types:α-cells: located in the outer rim of islet, secrete Glucagonβ-cells: located in the central part of the islet, secrete Insulin δ-cells: are found throughout the Pancreas and secrete Somatostatin and GastrinPP cells: produce less than 1% of Pancreatic polypeptide, which can act as Paracrine hormones (that act like Somatostatin)-Gap-junctions link β-cells to β-cells, α-cells to α-cells, and β-cells to α-cells to facilitate more rapid cell to cell communication.

-Pancreatic Endocrine Hormones--Glucagon (α-cells):-Glucagon secretion depends on blood level of glucose; low levels increase Glucagon secretion which increases blood glucose in response. Glucagon has receptors in the Liver and in Adipose tissue that stimulate the production of Glucose from stored Glycogen.-Glucagon is very efficient in small amounts, 1 g/kg of Glucagon elevates blood levels of Glucose by 20 mg/dl within 20 minutes.-Glucagon elevates blood glucose levels by increasing the rate of Glycogenolysis (Glycogen → Glucose) and inhibiting Glycogenesis (Glucose → Glycogen) in the Liver.-Glucagon also increases blood glucose by increasing Gluconeogenesis along with Cortisol. This process utilizes lactic acids, fatty acids, amino acids and glycerol to produce new glucose molecules. Lipolysis generates glycerol, fatty acids and ketoacids. Proteolysis generates amino acids from protein degradation, and any unused amino groups are dumped into urea (increasing urea production) for excretion in the urine.

-Somatostatin ( δ-cells) : Down-regulates Insulin and Glucagon by inhibiting their secretion, indirectly decreases peristalsis, indirectly decreases secretion and absorption in the GI tract by inhibiting Histamine and Gastrin action on G-cells, therefore inhibiting secretion in Parietal cells. Prolongs digestive window for nutrient

assimilation from the small intestine into blood.

-Insulin (β-cells):-Is increased when blood glucose levels are high to facilitate cellular uptake of glucose and decrease blood levels to normal (70-110 mg/dl)-Insulin has receptors in most types of tissue but most importantly in the: Liver, muscles, & Adipose tissue-target cell uptake of glucose from blood facilitates the production of ATP-Hyperglycemia increases Insulin secretion, while Hypoglycemia increases Glucagon secretion.-Hyperglycemia occurs when blood glucose exceeds 120 mg/dl - Insulin increases and Glucagon decreases-Hypoglycemia occurs when blood glucose drops below 50-60 mg/dl – Insulin decreases an Glucagon increases-When blood glucose is too high: >Insulin stimulates Glycogenesis (Glucose → Glycogen) in the Liver >Insulin inhibits Glycogenolysis (Glycogen → Glucose) and >Insulin decreases Gluconeogenesis by increasing levels of fructose-2,6-biphosphate by promoting phosphofructokinase enzyme activity. >Insulin decreases Lipolysis and increases fat storage, which decreases ketoacid formation by decreasing the acetyl CoA by-product formed by Lipolysis. >Decreases blood levels of K+ by closing cell membrane K+ channels during Glucose uptake

-Glycogenesis: creation of glycogen from glucose. Glucose->Liver->glucose-6-phosphate-> glucose-1-phosphate->Glycogen. Glycogen synthase enzymes catalyze this process. Glucagon is secreted by Pancreatic alpha-cells and stimulates the Liver to inhibit this process.

-Glycogenolysis: The reverse process, when the body needs more glucose, the Liver breaks down stored Glycogen back into Glucose. Glycogen->glucose-1-phosphate->glucose-6-phosphate->Glucose. Glucagon from Pancreatic alpha-cells stimulates Liver to begin this process.

-Gluconeogenesis: Stimulated by Glucagon and Cortisol. The formation of glucose from fatty acid, lactic acid, glycerol, and amino acid in the Liver, which is carried to the muscle for use.

-Pineal gland--Is located in posterior region of the 3rd ventricle of the brain and secretes Melatonin to control sleep. -The absence of light stimulates melatonin secretion to induce sleep. -As you age, Pineal glands may atrophy or calcify, causing sleep loss. >This can be treated with synthetic melatonin.-Melatonin Synthesis: Serotonin precursor is a neurotransmitter that is derived from its precursor, Tryptophan, an amino acid. Pineal cells install acetyl functional groups (Acetylation) and -CH3 groups (Methylation) onto Serotonin to convert it into Melatonin. This process is dependent on the amount of light exposure to the eyes, as abnormal light exposure inhibits this process and may result in sleep issues.

-The effects of Light-Dark exposure: When the retina of the eye is exposed to decreasing amounts of light (like when the sun is setting) it stimulates a signal to activate the Suprachiasmatic nucleus found in the Hypothalamus, which is an organ that regulates many biological processes including sleep and our natural

Circadian rhythm. Nerve fibers extend down the spinal cord to transmit the activation signal to the Superior Cervical Ganglia, which sends the signal back up the spinal cord along its post-ganglionic nerve fibers to innervate the Pineal Gland to begin hormone synthesis and secretion.

-Prostaglandins--Every cell has prostaglandin secretion, which can stimulate a wide variety of functions, including: >blood vessel – vasodilation & vasoconstriction >smooth muscle – contraction & relaxation > blood pressure regulation > inflammation regulation-Prostaglandin secretion increases: >During erections, where it vasodilates the dorsal vein in the penis. -Synthetic prostaglandin is used to treat Erectile Dysfunction. >During labor it dilates the cervix of the uterus >During menstruation it can irritate the pelvic cavity and cause pain-Prostaglandin-E2 can irritate the temperature center in the Hypothalamus and cause fever -Forms from the precursor Arachidonic acid which is converted by Cyclooxygenase enzyme -Common types of Prostaglandins (PG):-PGI2: active in Antiplatelet aggregation (inhibits blood clotting) and vasodilation-PGE2: active in smooth muscle relaxation, vasodilation, and is the causative agent in fevers -PGF2α: active in smooth muscle contractions and vasoconstriction >PGE2 and PGF2α both involved in uterine contractions during childbirth-TXA2 (Thromboxane-A2): active in platelet aggregation (blood clotting) and vasoconstriction

-Prostaglandin precursor Arachidonic acid can also be oxidized by Lipoxygenase enzyme to form Leukotrienes inside specialized leukocytes. Leukotrienes are mostly active in asthmatic reactions to induce bronchial inflammation, bronchoconstriction and vasoconstriction in the Respiratory System. -Leukotrienes and specialized Prostaglandins are usually synthesized at the same time as they act synergistically in Asthmatic inflammatory reactions.

-Prostaglandin Inhibitors:-Certain drugs can inhibit Cyclooxygenase enzyme from being able to catalyze Prostaglandin synthesis, including NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) like Aspirin, Ibuprofen, Naproxen, and Indomethacin (preferred for babies with heart conditions)

-Hormones of the Gonads and Placenta--Prolactin: prepares mammary gland for breast feeding-Precursors: for TSH, ACTH & GH secreted by Placenta-Growth factors: secreted by the Placenta, which are important for embryonic cell proliferation and growth-Relaxin: relaxes the Pelvic joints and prepares the pelvic cavity for pregnancy, relaxes cervix for delivery-Testosterone, Progesterone, and small amounts of Estrogen are also secreted by the Placenta-Estrogen- -Is secreted by the gonads once puberty begins, and from Placenta during pregnancy

-Estrogen in excess can suppress Testosterone and cause infertility in males-Estrogen is important in the development of genitalia in female fetus, for the development of the ovaries and the descent of ovaries from the abdominal cavity and into the pelvic cavity-Estrogen levels increase after menstruation for the regeneration of the Endometrium layer in the uterus.-Estrogen is important for the development of Secondary Sex Characteristics including breast development, changes in body shape, and the accumulation of fat for the rounding of the hips and legs. -Estrogen deficiency can cause depression, anxiety, nervousness, and infertility. -Before and during menstruation Estrogen levels decrease and commonly causing feelings of depression. -Depression caused by Estrogen deficiency can occur in menopausal and post-menopausal people due to Estrogen levels decreasing significantly and permanently.-Progesterone--Important for preparing and maintaining the Endometrium of the uterus for implanting a fertilized ovum. -Secretion is controlled by follicles that develop into the Corpus Luteum (of pregnancy) in the ovary, during the 1st trimester of Pregnancy. -In the 2nd & 3rd trimester, the control of Progesterone secretion is taken over by the placenta. -Progesterone deficiency can cause spontaneous abortion (miscarriage). -Testosterone--LH stimulation of the Leydig cells in testicles induces Testosterone secretion-High levels of Testosterone can inhibit LH secretion via negative feedback-A male sex hormone important in the development of testicles in the male fetus, and the descent of testicles from the abdominal cavity and into the scrotum during intrauterine life. -Controls the development and growth of genitalia after birth as well. -Dihydrotestosterone is another sex hormone complementary to Testosterone-Testosterone is important in the development and maintenance of Secondary Sex Characteristics during and after puberty, including muscle development, voice changes and increased libido -Controls production of sperm after puberty. -Testosterone deficiency can cause infertility and depression, since it controls mood to an extent (though emotions are also under the control of serotonin and dopamine neurotransmitters and the Limbic System) -Important for fluid absorption into the blood, in this way it has a hand in regulating blood volume -Testosterone can stimulate an increase in red blood cell production-Ovaries secrete small amounts of Testosterone since it is molecularly similar to Estrogen and can be converted into Estrogen via Aromatase enzyme. Adipose tissue can increase Aromatase levels, so obese males with Testosterone deficiencies may be infertile due to Aromatase catalyzed conversion into Estrogen.

-Chapter 16: The Reproductive System--Spermatogenesis: the production of mature sperm from germ cells, which is regulated by FSH. During pregnancy the embryo is connected to its yolk sac, which produces XY germ cells that migrate to the gonads (testes in males). In Spermatogenesis, the fetal germ cells are converted into Spermatogonia type A, which stay dormant within seminiferous tubules in the testes until puberty. During puberty Spermatogonia type B undergo Mitotic cell proliferation and growth to become diploid (XY) Primary Spermatocytes, which each undergo their first Meiotic reduction division to become 2 haploid (X or Y) Secondary Spermatocytes, which then undergo a second Meiotic division to become 4 haploid Spermatid, which eventually enter Spermiogenesis to mature into 4 Spermatozoa (sperm).

>FSH (Follicle Stimulating Hormone) in males: FSH has receptors on some cells in the testes, and controls maturation of sperm and Spermatogenesis from germ cells. When the rate of sperm production is too high, Sertoli cells secrete Inhibin to prevent FSH from sending feedback to the Anterior Pituitary (for more FSH), in this way it inhibits further FSH secretion.

>LH (Luteinizing Hormone) in males: LH has receptors on specific testicular cells called Leydig cells. LH binding to these receptors stimulates secretion of Testosterone (used in reproductive regulation & puberty) -Oogenesis- -Oogenesis is controlled by FSH and LH, which are both controlled by GnRH.-The development of mature Oocytes from germ cells. During embryonic development, germ cells (XX) migrate to the primitive gonads of the fetus (the ovaries), during week 4 of pregnancy. Then the germ cells are converted into Oogonia, which begin Mitotic cell division to proliferate (as opposed to sperm which begin Mitosis during puberty). After proliferation the Oogonia grow and develop into Primary Oocytes, collecting an outer single layer of connective tissue that later becomes a follicle. The Primary Oocyte begins its first Meiotic division during fetal life but does NOT complete it. Female newborns are therefore born with a limited number of Primary Oocytes “arrested” in Meiosis I . The Primary Oocyte stays dormant due to follicular cell secretions of Oocyte Maturation Inhibitor (OMI) until puberty, where it then continues to enlarge, and the single layer of connective tissue cells around it develops into cuboidal epithelial cells to form a protective Primary Follicle. Further maturation of the follicle into a Secondary Follicle results in stratified cuboidal epithelia. During puberty, once a follicle begins this maturation process, the Primary Oocyte inside grows and completes its first Meiotic cell division, becoming a Secondary Oocyte, where it stays “arrested” until Ovulation. Upon ovulation a single Secondary Oocyte (sometimes 2 or more) will begin Meiosis II but will NOT complete this second Meiotic division unless fertilization occurs. -If fertilization occurs then the second Meiotic division completes, and the Secondary Oocyte becomes a fertilized oocyte (also called a Zygote, or mature ovum).-If fertilization does NOT occur, then menstruation follows ovulation, and the Secondary Oocyte is shed along with the Endometrial lining of the uterus.-Typically, one follicle containing one Primary Oocyte matures per monthly ovulation cycle

-Birth control: can cause a reduction in Oocyte maturation, although by the age of 50-55 there is a complete reduction in Primary Oocytes which causes the onset of Menopause, where infertility is permanent. Contraceptives can increase blood pressure and may cause hypertension, acne, weight gain, emotional changes, and decreased or inhibited menstruation. Contraceptive pills typically consist of synthetic Estrogen and Progesterone, which suppresses FSH to inhibit ovulation and the menstrual cycle by mimicking the hormone levels present during pregnancy. This false pregnancy state keeps the ovary from maturing follicles and oocytes for fertilization, since in a real pregnancy this would cause a miscarriage.

-FSH (Follicle Stimulating Hormone) & LH (Luteinizing Hormone) in females: see menstruation & ovulation

-The testes- -Sertoli cells: line the inner wall of Seminiferous Tubules and help regulate Spermatogenesis via Inhibin secretion to regulate FSH levels. These cells DO NOT divide-Leydig cells: secrete Testosterone as a response to LH secretion. The highest level of Testosterone secretion occurs during the morning.

-Female Fertility--The Menstrual Cycle: goes through 3 phases over 28 days.-1 st Phase ( Follicular ): First 2 weeks of the cycle, FSH levels increase to mature a follicle in the ovary-2 nd Phase (Luteal Phase): FSH decreases and LH increases during the midcycle (days 13-15), and Ovulation begins about 12-24 hours following the increase in LH. The follicle develops an avascular spot (without blood supply) called the Stigma, where the follicle ruptures to release the Secondary Oocyte. The remnants of the follicle convert into Corpus Luteum, which secretes Progesterone and Estrogen to help maintain and prepare the Endometrium of the uterus for the possible implantation of a fertilized egg. The Secondary Oocyte, covered in two layers, the Zona Pellucida and Corona Radiata, wait in the Ampulla of fallopian tubes for possible fertilization. -the Zona Pellucida is a protective layer around the Oocyte that consists of glycoprotein material-the Corona Radiata is a protective layer around the Zona Pellucida that consists of follicular cells-3 rd Phase (Secretory Phase) : If no fertilization occurs then Estrogen levels drop, and menstruation occurs to shed the prepared layer of Endometrium and the unfertilized Secondary Oocyte. The Corpus Luteum degrades over 10-12 days following ovulation, becoming scar tissue called the Corpus Albicans. Lasts 5-7 days. After menstruation, Estrogen levels increase again for the regeneration of the Endometrium and the development of another ovum.

-Ovulation: Occurs on days 13-15 of the menstrual cycle and is under the control of LH. If any sperm are present during these days, the ovum has a much higher chance of being fertilized. If fertilization occurs the Corpus Luteum grows into the Corpus Luteum of Pregnancy and increases Progesterone secretions. These secretions are under the control of human Chorionic Gonadotropin (hCG), which stimulates the Corpus Luteum to maintain specific levels of Progesterone secretion during the first trimester while the Placenta develops.-After the first week of pregnancy implantation of the ovum into the endometrium of the uterus occurs, and the formation of the primitive placenta begins. Placenta secretes hCG and maintains the Corpus Luteum during the first trimester. Corpus Luteum secretes Progesterone during the first trimester and then degenerates at the end of the first trimester, so the Placenta takes over Progesterone production for the rest of the pregnancy. -Progesterone deficiency in pregnant females can cause spontaneous abortion (miscarriage) . -If there is no sperm present during ovulation or no fertilization occurs after day 15, the Corpus Luteum degenerates into scar tissue called the Corpus Albicans. LH and Estrogen levels then decrease, and the unfertilized ovum and endometrial tissue layer are shed over the course of 5-7 days during menstruation.-After menstruation FSH and Estrogen levels increase again to start the process over.

-The Female Reproductive System: The uterus has a fundus and body, the wall has 3 layers: Perimetrium, Myometrium, and Endometrium. The Endometrium is full of blood vessels. There are some ligaments supporting the structures and holding them in suspension within the pelvic bowl. For example: the ovarian ligament allows the ovary to be suspended above the uterus but still be directly attached to it (keeps ovary in place so it doesn’t get tangled with the fallopian tube). The fallopian tube covers the ovary with extensions called Fimbriae. The cervix is the lower opening of the uterus into the vagina.

-Labor and Parturition- -The duration of the pregnancy and childbirth is under the control of specific hormones.-Oxytocin causes uterine contractions and the dilation of the cervix to allow the fetus to move into the vaginal canal.-Prostaglandins control labor and delivery: >Prostaglandin-F2α (PGF2A): stimulates smooth muscle contractions and vasoconstriction >Prostaglandin-E2 (PGE2): stimulates smooth muscle relaxation and vasodilation

-hCG (human Chorionic Gonadotropin):-hCG binds to cell-surface receptors on follicle cells -hCG controls the follicle cells in the Corpus Luteum after fertilization to control the secretion of Progesterone, which helps to maintain and prepare the Endometrium layer of the uterus for implantation of the fertilized egg. hCG regulation of Progesterone is important during pregnancy, as a decrease can lead to spontaneous abortions (miscarriage) .