Physiology of Endocrine System Lectures 2024 PDF

PHYSIOLOGY Physiology of Endocrine System Dr. Salah Al-shuaiby M.B.B.S , MSc in medical physiology, MD.Diagnostic Radiology (assistant professor ) 2024  Intruduction Endocrinology is a study of the endocrine glands and their...

PHYSIOLOGY Physiology of Endocrine System Dr. Salah Al-shuaiby M.B.B.S , MSc in medical physiology, MD.Diagnostic Radiology (assistant professor ) 2024  Intruduction Endocrinology is a study of the endocrine glands and their functions. The endocrine system is one of the control systems in the body. Functions of the endocrine system: The endocrine system controls: 1- Development and Growth. 2- Energy regulation (storage & mobilization). 3- Internal homeostasis (fluids, ions). 4- Reproduction (menstruation, pregnancy, lactation). 5- Control responses to stress and immune system.. Other functions:  Control Heart rate & blood pressure by catecholamines and thyroxine.  Control Appetite & sleeping and waking cycles by leptin and melatonin. Dr.Salah AL-SHUAIBY  Major Endocrine Glands & Organs  Endocrine gland:  Are glands of the endocrine system that secrete their products (hormones) directly into the blood rather than through a duct (ductless). Or: it’s mainly group of cells that secrete hormones to the interstitial fluid, to the blood, to different targeted organs & cells. Dr.Salah AL-SHUAIBY Major Endocrine Glands & Organs Dr.Salah AL-SHUAIBY  Major Endocrine Glands & Organs 1- Hypothalamus A connection between nervous and endocrine system. Connected to pituitary gland. Controls anterior pituitary gland. By releasing control hormones (by hypothalamo -hypophyseal portal circulation ) a) Releasing hormones. b) Inhibitory hormones. Secretes hormones. Send hormones to posterior pituitary gland (by hypothalamo -hypophyseal tract) a) ADH : through supra Optic chiasm nucleus. b) Oxytocin : through para palpator ventricular nucleus. Has adrenaline center. Control adrenal medulla that secrete adrenaline and noradrenaline. Dr.Salah AL-SHUAIBY  Major Endocrine Glands & Organs 2- Pituitary gland (hypophysis cerebri) A.Anterior : control other glands (slow) a) Thyroid gland : has generalized action b) Suprarenal [adrenal] cortex : Has specific action c) Gonads :have specific action I. testes in male II. ovaries in female B. Posterior : store ADH and oxytocin. 3- Parathyroid glands. rapid & uncontrolled 4- Endocrine pancreas. rapid & uncontrolled Dr.Salah AL-SHUAIBY  Major Endocrine Glands & Organs 5- Organs with endocrine function - Certain organs contain endocrine cells that synthesize and release hormones, thus adding an endocrine function to these organs. Examples: a- Liver: secretes [Erythropoietin, somatomedines, vitamin D (calcidiol)]. b- Kidney: secretes [Erythropoietin, active form of vitamin D (calcitriol)]. c- Gastrointestinal tract: secretes [e.g. Gastrin, Secretin, CCK, etc] d- Heart : atrial natriuretic peptide (ANP) e- Pineal gland: secretes melatonin hormone. f- Placenta: secretes [Estrogen, Progesterone, Relaxin, HCG, HCS]. g- Skin : secretes [leptin , vitamin D (cholecalciferol )]. h- Adipose tissue. secretes : Leptin is involved in appetite control, and stimulates increased energy. expenditure reduce dietary intake and fat storage. Adiponectin – enhances sensitivity to insulin.  Hormones Definition : ž Hormone is a chemical substance released by group of cells to control the function of other type of cells. Types of hormones: ž Affect many different types of cells (eg. GH and Thyroxin) Affect only specific target cells (eg. ACTH and estrogen) Endocrine glands essential for life ž Deficiency of their hormones causes death in a short time. These include: - The anterior lobe of the pituitary gland ( “ACTH”) - The adrenal cortex (Cortisol) - The parathyroid gland (PTH) What are target cells? ž Target cells refer to cells that contain specific receptors (binding sites) for a particular hormone. Dr.Salah AL-SHUAIBY Endocrine Hormones  Chemical Messengers: 1-Endocrine are released by glands or specialized cells into the circulating blood and influence the function of target cells at another location in the body. 2-Neuroendocrine are secreted by neurons into the circulating blood and influence the function of target cells at another location in the body. a) Neurotransmitters: Ach, dopamine b) Neurohormones : vasopressin or norepinephrine. 3-Paracrines are secreted by cells into the extracellular fluid and affect neighbouring target cells of a different type. 4-Autocrines are secreted by cells into the extracellular fluid and affect the function of the same cells that produced them. Dr.Salah AL-SHUAIBY  Classification of hormones (chemical) 1. Protein and peptide hormones: Synthesized from amino acids & They're stored in secretory vesicles until needed Examples: a) Pituitary hormones. b) Parathormone. c) Pancreatic hormones. d) Hypothalamic hormones 2-Steroid hormone:. Derived from cholesterol &They diffuse across the cell membrane (lipophilic), so they're not stored. Examples: a) Adrenocortical hormones [Cortisol, Aldosterone, Androgens]. b) Sex hormones [Estrogen, Progesterone, Testosterone]. 3-Amine hormone: derived from one amino acid (Tyrosine). Examples: a) Thyroid hormones [T3 & T4]. b) Adrenomedullaryhormones (catecholamines) [Adrenaline & Noradrenaline]. Dr.Salah AL-SHUAIBY  1. Protein and peptide hormones: ❖ Synthesized as preprohormone post-translational modification to prohormone then hormone. ❖ Example of protein hormone: Insulin. 1- In the nucleus, the gene for the hormone is transcribed into an mRNA. 2- The mRNA is transferred to the cytoplasm and translated on the ribosomes to the first protein product, a preprohormone. 3- The signal peptide is removed in the endoplasmic reticulum, converting the preprohormone to a prohormone. 4- The prohormone is transferred to the Golgi apparatus, where it is packaged in secretory vesicles. In the secretory vesicles, proteolytic enzymes cleave peptide sequences from the prohormone to produce the final hormone. 5- The final hormone is stored in secretory vesicles until the endocrine cell is stimulated. Dr.Salah AL-SHUAIBY  2-Steroid hormone: Are made from cholesterol, are lipophilic & can enter target cell. Are immediately released from cell after synthesis. Interact with cytoplasmic receptors. Activate genes (DNA) for protein synthesis. Are slower acting and have longer half-life than peptide hormones. Examples: cortisol, estrogen & testosterone Dr.Salah AL-SHUAIBY  3-Amine hormone: Derived from tyrosine or tryptophan (One type of amino acid (tyrosine).) 3 groups: ž 1. Tryptophan → Melatonin 2. Tyrosine → Catecholamines ○ behave like peptide hormones 3. Tyrosine → Thyroid hormones ○ behave like steroid hormones Dr.Salah AL-SHUAIBY Classification of Stimuli Dr.Salah AL-SHUAIBY Humoral Stimuli Dr.Salah AL-SHUAIBY Neural Stimuli Dr.Salah AL-SHUAIBY Hormonal Stimuli Dr.Salah AL-SHUAIBY  Transport of hormones dissolve in blood then move through openings in the endothelium to reach the targeted cell & attach to the receptor to produce action. Action of the protein hormones either direct on the cytoplasm or through the nucleus & produce gene regulation. - Steroid hormones are traveled in blood combined with protein & once it reaches the targeted cell it will be released from the protein to produce it’s action (needs to go through the nucleus to produce gene regulation). -Takes long time to produce action. - If steroids is low in blood & we give external hormones the action will take a long time.  Transport of hormones 1. The lipid insoluble (water soluble) hormones : a) Catecholamines (epinephrine and norepinephrine) b) Peptide/protein hormones. a) Pituitary hormones. b) Parathormone. c) Pancreatic hormones. d) Hypothalamic hormones. 2. The lipid soluble hormones : a) Thyroid hormones b) Steroid hormones a) Adrenocortical hormones: [Cortisol, Aldosterone, Androgens]. b) Sex hormones [Estrogen, Progesterone, Testosterone].  Receptors: Hormonal receptors are large proteins. 2000-100,000 receptors/cell. Receptors are highly pecific for a single hormone. Receptor’s Location: 1. Cytosolic or Nuclear: Lipophilic ligand enters cell. Often activates gene. Slower response (Due the time consuming transcription & translation processes). Example: In the cell cytoplasm (Steroids). In the cell nucleus (thyroid hormones). 2. Cell membrane (surface): Lipophobic ligand can't enter cell. Outer surface receptor. Fast response (The binding of the ligand to the receptor will cause a cascade of actions). Example: proteins, peptides & catecholamines.  Regulation of hormonal receptors (Receptors does not remain constant): Inactivated or destroyed. Reactivated or manufactured. And they undergo: 1. Up-regulation: The hormone induces greater than normal formation of a receptor or intracellular signaling proteins.Lead to: 1. Increase synthesis. 2. Decrease degradation. 3. Activation. EXAMPLE : GH, prolactin (For breast-milk synthesis; once it’s secreted the number of the receptors will increase hence,increase the breast-milk production). 2. Down-regulation: (Used in case of primary hyperthyroidism; no negative feedback mechanism to regulate the hormone release. So, we down-regulate the receptor using one of these mechanisms). Increase hormone concentration leads to: 1. decrease in the number of active receptors & synthesis. 2. Increase degradation. 3. Inactivation. EXAMPLE :T3 hormone.  Mechanism of actions of hormones Hormones are working on proteins which are 2 types : 1. Enzymes : by activation of enzymes Or 2. Channels : by opening of channels. Either directly or by G protein Lipid soluble hormones>> synthesis of protein >> slow Lipid insoluble hormones >> activation of proteins>>fast  G-protein Cell membrane protein. Connected to guanosine. It’s inactive, If connected to guanosine diphosphate It’s Active, If connected to guanosine triphosphate Is a regulatory protein which is 2 types: 1. Stimulatory G proteins: Stimulate enzymes Open the channels 2. Inhibitory G proteins : Inhibit enzymes Close the channel Mechanism of action of hormones & target tissue Target tissue :Target cells refer to cells that contain specific receptors (binding sites) for a particular hormone. Each hormone has it’s own specific receptors on target cells. Peptide and Protein Hormones 1-Hormone-receptor interaction (1st messenger) 2- Enzyme activation. 3- Release of the second messenger: (a) Adenylate Cyclase-cAMP. (b) Phospholipase C-IP3/DAG. (c) Calcium-calmodulin complex. (d) Tyrosine Kinase System. 4-Effects on cellular function Dr.Salah AL-SHUAIBY  A-Second messenger (Adynylate cyclase-cAMP): 1. Hormone binds with the receptor on cell membrane 2. The receptor is bound to G-protein which is bound to GDP after the hormone is connected with the receptor the G-protein will get activated by acquiring GTP and releasing GDP (enzyme activation) 3. The changes to G-protein will make it move across the cell membrane to the adenyl cyclase receptor that will convert ATP to cAMP (release of secondary messenger) 4. cAMP will then activate protein kinase which will cause the effect on cellular functions  B-Second messenger (Phospholipase C-IP3): 1. Hormone binds with receptor that is connected to inactivated g-protein (bound to GDP). 2. The binding will activate the G-protein which will move across the membrane to activate the phospholipase C (enzyme activation), then cleaves the inositol phospholipid into two parts IP3 and DAG. 3. The IP3 (secondary messenger) will go to the endoplasmic reticulum and stimulate the release Ca, the increase of Ca will cause the effect on cellular functions. Dr.Salah AL-SHUAIBY  C- Second messenger (calcium-calmodulin complex): 1. Receptor operated by a ligand (hormone). The binding will cause a conformational change that will allow the Ca to enter the cell. 2. Once Ca level inside the cell rises, Ca will bind to calmodulin and form calcium-calmodulin complex (secondary messenger). 3. Ca-calmodulin complex will activate protein kinase by phosphorylation. Activated protein kinase will phosphorylate Protein-P and then will cause several cellular changes.  D- Second messenger (Tyrosine Kinase System): Is used by insulin & many growth factors to cause cellular effects. Surface receptor is tyrosine kinase. ○ Consists of 2 units that form active dimer when insulin binds. Activated tyrosine kinase phosphorylates signaling molecules. Induction of hormone/growth factor effects. Tyrosine kinase receptor has two domains, when insulin binds to the receptor the domains will come together (dimerization). Activation will cause phosphorylation of the receptor by ATP, and the receptor will phosphorylate other signaling molecule that will produce the action of insulin which is opening some channels that brings glucose inside the cell. Dr.Salah AL-SHUAIBY Mechanism of action In case of steroid & thyroid hormones  Regulation of Hormone Secretion* Regulation of hormone secretion by neural or feed back mechanism 1-Negative feedback means that some feature of hormone action, directly or indirectly, inhibits further secretion of the hormone. Release of hormone A stimulates the release of hormone B→Hormone B inhibits the release of hormone A. For example, LH from pituitary stimulates the testes to produce testosterone which in turn feeds back & inhibits LH secretion. - Short loop: the feedback is directly on the chief gland secreting it. - Long loop: when the feed back is all the way back to the hypothalamus. - Ultra-short loop: the gland secretes hormone & that’ll directly act on it “autocrine”.  Regulation of Hormone Secretion* 2-Positive feedback Means that some feature of hormone action causes more secretion of the hormone. - Release of hormone A stimulates the release of hormone B →Hormone B stimulates further release of hormone A. For examples: include LH stimulation of estrogen which stimulates LH surge at ovulation. - “Self- augmenting” Hormone release will further increase its secretion. E.g. oxytocin will cause uterus contraction & lead to cervix expansion which will further increase oxytocin release.  Clearance of hormones: - Two factors control the concentration of a hormone in the blood: (Hormones have half-life that’s why we need them to be regularly synthesized). 1. The rate of its secretion (release). 2. The rate of its inactivation & removal (metabolic clearance). Hormones are cleared by: 1. Metabolic destruction by tissues. 2. Binding with tissues. 3. Excretion by the liver into bile. 4. Excretion by the kidney into urine. Clearance of protein bound hormones is slower than clearance of peptide hormones - So if the rate of secretion is greater than the removal high levels of the hormones in blood. - steroid hormones are slow because they are attached to proteins while peptide hormones are fast.  Hypothalamus -Hypothalamus is located at the base of the brain & Composed of number of nerve cells. - It is part of the limbic system, which controls the autonomic nervous system and the endocrine systems. Hypothalamus Composed of number of nerve cells. Hypothalamic-Pituitary Axis: coordinate Thyroid gland, adrenal gland & reproductive gland. It also controls growth, milk production and osmoregulation. ❖ Hypothalamic control of pituitary gland by: - Hypothalamo-hypophyseal portal system/ portal vessels/circulation - Hypothalamo-hypophyseal tract/ neural tract / neural axons ❖ Almost all secretions by the pituitary are controlled by either: - Hormonal secretion of hypothalamus to the portal system to (Anterior pituitary). - Nervous signals from hypothalamus to the neural tract to (Posterior pituitary).  Control of Posterior Pituitary By Hypothalamus: Collection of nerve axons + supporting cells (Straight forward neural relationship). Supraoptic nuclei. 1. Antidiuretic hormone (ADH) (vasopresson) For water regulation. Paraventricular nuclei. 2. Oxytocin :For production of milk &contraction of uterus. Hormones release from posteriorpituitary are synthesis in hypothalamus and go all the way to posterior pituitarythrough tract, and than release from posterior pituitary into blood. Dr_ Salah AL-shuaiby  Control of Anterior Pituitary By Hypothalamus: 1- Anterior pituitary gland is connected to hypothalamus by portal system: “hypothalamic- hypophyseal portal vessels” 2-Special neurons in the hypothalamus synthesize and secrete the hypothalamic releasing and inhibitory hormones that control secretion of anterior pituitary. Both neural and endocrine control. 3- Neurons send their nerve fibers to the median eminence (extension of hypothalamic tissue into the pituitary stalk). 4- Hormones are secreted to the tissue fluids, absorbed into the hypothalamic-hypophyseal portal ystem and transported to the sinuses of the anterior pituitary.  Hypothalamic Releasing and Inhibiting Hormones of Anterior Pituitary 1- Growth hormonereleasing hormone(GHRH) & Growth hormone inhibiting hormone(GHIH) (somatostatin.) GHRH Stimulates release of Growth Hormone. GHIH inhibit release of Growth Hormone. - Hypothalamus will secrete GHRH that will act on Anterior pituitary to stimulate secretion of GH. -GH will reach bloodstream and reach target tissue to cause its effect. A byproduct of GH is called somatomedin. Majority of GH acts by somatomedin (indirect), and the rest acts direct. 1- GHRH inhibits its own secretion from the hypothalamus via an ultrashort loop feedback 2- Somatomedins inhibit secretion of GH by ant.p. 3- Both GH & somatomedin stimulate secretion of somatostatin by the hypothalamus. The overall effect is inhibitory (negative feedback) because somatostatin inhibits GH secretion. Dr_ Salah AL-shuaiby Thyrotropin releasing hormone (TRH) ❖ function: Stimulates the release of Thyroid Stimulating Hormone (TSH). It will be secreted by hypothalamus and act on thyrotrophs of anterior pituitary gland to cause secretion of TSH. - TSH then acts on thyroid gland to stimulate secretion of T3 and T4 (thyroid hormones). T3 and T4 inhibit secretion of TSH (-ve feedback) Dr_ Salah AL-shuaiby  Corticotropin releasing hormone (CRH) ❖ function : Stimulates the release of Adrenocorticotropic Hormone (ACTH). - CRH will act on corticotrophs of anterior pituitary gland to secrete ACTH. - ACTH which will work on adrenal cortex and cause secretion of adrenocortical hormones. This will feedback on hypothalamus and Ant pituitary to inhibit further release of hormone. -main stimulus of prolactin secretion is limitation of dopamine compared to TRH Dr_ Salah AL-shuaiby Gonadotropin releasing hormone(GnRH) ❖ function Stimulates the release of two gonadotropic hormones: ❖ Luteinizing hormone (LH). ❖ Follicle-stimulating hormone (FSH). - GnRH is secreted by the hypothalamus and acts on gonadotrophs of the anterior pituitary gland can cause secretion of LH and FSH that will work on gonads (ovary/testicles). Dr_ Salah AL-shuaiby Prolactin inhibitory hormone (PIH)(Dopamine) function : Inhibit the secretion of Prolactin. There are two regulatory pathways from hypothalamus: 1) inhibitory via dopamine and 2)stimulatory via TRH. In persons who are not pregnant or lactating, prolactin secretion is tonically inhibited by dopamine (PIF) from the hypothalamus. The inhibitory effect of dopamine dominates and overrides the stimulatory effect of TRH. Dr_ Salah AL-shuaiby Hypothalamic Releasing and Inhibiting Hormones of Anterior Pituitary Clinical Application* Cutting pituitary stalk Cutting the connection between the hypothalamus & ant. Pituit. results in inhibition of all the ant. pituit. hormones except prolactin  Why? Dr_ Salah AL-shuaiby Summary  Pituitary gland Pituitary gland (Hypophysis): is a 1cm gland that weigh 0.5-1g. The pituitary gland lies in the sella turisca In the anterior cranial fossa It consists of two parts : Anterior pituitary gland (Adenohypophysis) Posterior Pituitary gland (Neurohypophysis) Origin of Pituitary [embryology]: Anterior pituitary originates from Rathke's pouch ( pharyngeal epithelium ) Posrterior pituitary originates from hypothalamus (glial-type cells) [remember it’s neural tissue so it originates from neuroectoderm] Dr_ Salah AL-shuaiby  Anterior pituitary gland ⚫ There are 5 cell types in the anterior pituitary : ⚫ Somatotrophs secrete GH ⚫ Thyrotrophs secrete TSH ⚫ Gonadotrophs secrete FSH & LH ⚫ Corticotrophs secrete ACTH. ⚫ Lactotrophs secrete Prolactin Dr_ Salah AL-shuaiby  Anterior pituitary gland Anterior Lobe of pituitary gland is called “ Adenohypophysis”: Adeno = Glandular part Hypophysis = Pituitary gland Anterior pituitary gland is connected to hypothalamus by portal system: “ hypothalamic-hypophyseal portal vessels ”. 6 Hormones are secreted by the ant pituitary gland: 1-growth hormone. 2- Prolactin. 3-ACTH= Adrenocorticotropichormone. 4 - TSH=Thyroid stimulating hormone. 5- FSH= FOLLICLE STIMULATING HORMONE 6- LH = LEUTINIZING HORMONE Dr_ Salah AL-shuaiby Growth Hormone(Somatotropin) Mechanism of action: Dr_ Salah AL-shuaiby  Functions of GH: A) Long term effects (Promotion of growth): (takes years to occur) - Increase cellular sizes & mitosis - Increase tissue growth & organ size (Increased Chondrogenesis and Increased Osteoblastic activity) Bone growth: Mechanisms of bone growth 1. Linear growth of long bones: Long bones grow in length at epiphyseal cartilages, causing deposition of New Cartilage ( collagen synthesis) followed by its conversion into bone. When bony fusion occurs between shaft & epiphysis at each end, no further lengthening of long bone occur. 2. Deposition of New Bone ( cell proliferation) On surfaces of older bone & in some bone cavities, thickness of bone. Occurs in membranous bones, e.g. jaw, &skull bones. Dr_ Salah AL-shuaiby Bone growth:  B. Short term: (occurs daily)Metabolic effects: Protein metabolism (Anabolic): Increase rate of protein synthesis in all cells through: Increase amino acids transport into cells. Increased nuclear transcription of DNA to form RNA. Enhancement of RNA translation to cause protein synthesis. Decrease protein catabolism “protein sparer”. (because fatty acids are used as an energy source instead of proteins) Increases lean body mass. Fat metabolism (Catabolic): Increase mobilization of free fatty acids from adipose tissue stores. Conversion of fatty acids to acetyl CoA to provide energy. Stimulate triglyceride breakdown and oxidation in adipocytes. (Provides Fats as a Major Energy Source (Ketogenic effect) Dr_ Salah AL-shuaiby  B. Short term: (occurs daily) CHO metabolism (Hyperglycemic): Decreases glucose uptake by tissues (skeletal muscles and fat). Decreases the rate of glucose utilization throughout the body. (fat is the alternative of glucose for energy). Increases glucose production by the liver. (↑gluconeogenesis) Increases Insulin resistance (↑FFA2) insulin resistance (anti-insulin activity) “Diabetogenic”. -GH prevents the activation of Glut-4 by insulin, which stops the transport of glucose from blood into cells. Dr_ Salah AL-shuaiby  Other effects of growth hormone: - Increases calcium absorption from GIT. - Strengthens and increases the mineralization of bone. - Retention of Na+ and K+. - Increases muscle mass. - Stimulates the growth of all internal organs excluding the brain. - Contributes to the maintenance and function of pancreatic islets Stimulates the immune system. Dr_ Salah AL-shuaiby  Control of GH secretion: 1. The hypothalamus: a. GHRH : increase GH secretion. (Somatoliberin) b. GHIH (somatostatin): decrease GH secretion 2. Hypoglycemia (fasting): ↑ GH secretion. (N.B. glucose intake : ↓GH secretion). 3. Muscular exercise : ↑GH secretion. 4. Deep sleep: more in children. ↑GH secretion. 5. Stress conditions, e.g. trauma or emotions ↑ GH secretion. 6. Testosterone & estrogen increase GH secretion. 7. FFAs: ↓ GH secretion 8. Grelin (stomach): ↑GH secretion. Grelin is a hormone secreted by the stomach. Dr_ Salah AL-shuaiby Abnormalities of GH secretion  Dwarfism Deficiency of GH before puberty causes dwarfism (characterized by short stature with intact mental function) whereas deficiency of GH after puberty causes minor metabolic abnormalities and increased sensitivity to insulin.  Def. of GH. in adults ⚫ Deficiency of GH in adults ( after closure of epiphysis ) will lead toPremature Aging. ⚫ Reduced muscle mass and exercise capacity – Increased body fat. – Reduction in bone mineral density. – Wrinkling of skin. – Dyslipidemia. – Increased risk of vascular disease  Prolactin Synthesized by lactotrophs (15%) Chemically, prolactin is related to growth hormone, having 198 amino acids. - In addition to the anterior pituitary, it is also secreted by the endometrium & the placenta. The major function of prolactin is milk production. Prolactin release is inhibited by PIH (dopamine). - In persons who are not pregnant or lactating, prolactin secretion is tonically inhibited by dopamine. Suckling response inhibits PIH release leading to increase prolactin release. Dr_ Salah AL-shuaiby  Regulation of secretion - TRH → stimulates the production of prolactin - Dopamine → inhibits the production of prolactin. - Prolactin Stimulates the secretion of dopamine in median eminence (inhibits its own secretion) (negative feedback). - other than breastfeeding, the hypothalamus continuously secrets dopamine (Tonic inhibition) - Breastfeeding→ will inhibit the inhibitor which is Dopamine. Dr_ Salah AL-shuaiby  function of prolactin Effect on the breast - The major function of prolactin is milk production - Breast development. (Increase in all factors that make mammary glands produce milk ) - Lactogenesis. (Lactose, lipid, casein) Parturition. - Increases mRNA and Increases production of casein and Lactalbumin. - Other effects: Stimulates the secretion of dopamine in median eminence (inhibits its own secretion) During Pregnancy: Growth of mammary glands. (no milk production due to the inhibitory effect of placental hormones) (The high levels of estrogen and progesterone, which are required to maintain pregnancy, will inhibit milk production) After delivery: PRL initiates and maintains milk production. (suckling stimulation. PRL release) The placenta detaches -> estrogen and progesterone levels will decrease -> Prolactin will increase.  function of prolactin Gonadotropins: inhibits the effects of gonadotropins (Inhibition of ovulation “GnRH”). Decreases the sensitivity of ovaries to gonadotropins FSH / LH leading to suppression of menstrual cycle. Occurs in 50% of lactating women, physiological birth control. As long as she is lactating their will be no ovulation and no menstruation because of the gonadotrophins inhibition, but this is not sufficient for birth control, abolishing of gonadotrophins inhibition can occur and ovulation happens while the menstruation is absent and she gets pregnant because ovulation appears before menstruation. Why will it lead to infertility? Increase in Prolactin -> Inhibit the release of GnRH from hypothalmus -> derease in LH and FSH -> No ovulation or menstrual period. Control of secretion Dr_ Salah AL-shuaiby  Abnormalities PRL excess: - Caused by pituitary tumors (chromophobes adenoma). - Characterized by: o Infertility in both males and females due to inhibition of gonadotropin effects. o Amenorrhoea in females (absence of the menstrual cycle). o Impotence & loss of lipido in males. o Osteoporosis in females (due to low estrogens resulting from the inhibition of gonadotropins). o Galactorrhoea (milk production). Excessive prolactin Treated by Bromocriptine (Dopamine agonist). Prolactin deficiency → Failure to lactate. Dr_ Salah AL-shuaiby  ADRENO-CORTICOTROPHIC HORMONE (ACTH) Characteristics - A single chain polypeptide (39 amino acids); synthesized from Corticotrophs in the anterior pituitary. Control CRH released from the hypothalamus and stimulate the Ant.pituitary gland to release another hormone(ACTH) that act on adrenal cortex so they release Cortisol , and it will cause the negative feedback when it’s increased to maintain it within the normal value. Dr_ Salah AL-shuaiby  Factors affecting the secretion Stimulatory factors: all types of stress: (physical stress “exercise”, emotional stress “fear”, hypoglycemia, cold exposure and pain. - Decreased blood cortisol level. Inhibitory factors: Increase blood cortisol level. Effects of ACTH - Trophic effect on the adrenal cortex: Increases cellularity, vascularity and secretion of cortisol from the adrenal cortex. - increases the responsiveness of the adrenal cortex to subsequent doses of ACTH. - Pigmentation of the skin. Dr_ Salah AL-shuaiby  Abnormalities Excess ACTH: - Caused by: o Pituitary tumors that secrete ACTH (= cortisol excess of secondary Cushing’s syndrome). o Lung tumors that secrete ACTH (= cortisol excess of ectopic Cushing’s syndrome) , o Adrenal problems causing cortisol deficiency due to loss of the negative feedback on the pituitary (= Primary Addison’s disease). Deficiency of ACTH: - Caused by: o Pituitary tumors, which destroy the cells that secrete ACTH. (= decreased cortisol secretion from the adrenal cortex = secondary Addison’s disease) o Diseases of the adrenal cortex that cause excessive cortisol secretion. (= primary Cushing’s disease) are associated with low ACTH due to the negative feedback mechanism. Dr_ Salah AL-shuaiby  THYROID STIMULATING HORMONE (TSH) Characteristics - Glycoprotein (211 amino acids) consisting of two subunits: alpha & beta. Regulation: - From the hypothalamus by thyroid releasing hormone (TRH). - Negative feedback mechanism by TSH itself (short loop –ve feedback) & by the thyroid hormones from the thyroid gland (long loop –ve feedback). Dr_ Salah AL-shuaiby  (TSH) Factors affecting the secretion o Stimuli: Cold o Inhibitors: Heat and stress Effects 0Trophic effect on the thyroid gland: Increases cellularity, vascularity and secretion of thyroid hormones from the thyroid gland. Abnormalities TSH excess - Caused by: o Pituitary tumors that secrete TSH (= high T3 & T4 = secondary hyperthyroidism) o Thyroid diseases that decrease T3 & T4 secretion (= primary hypothyroidism) TSH deficiency - Caused by: o Pituitary tumors that decrease T3 & T4 secretion (= secondary hypothyroidism) o Thyroid diseases that increase T3 & T4 secretion (= primary hyperthyroidism) Dr_ Salah AL-shuaiby FOLLICLE STIMULATING HORMONE (FSH) & LEUTINIZING HORMONE (LH) Characteristics - Known as gonadotrophins “or gonadotropins” because of their trophic effects on the gonads. - They are glycoproteins. Each consists of 2 subunits: alpha & beta (similar to TSH & hCG). - Half life: FSH= 3 hours and LH= 1 hour. Control of secretion o From the hypothalamus by the gonadotrophin releasing hormone(GnRH). o Negative feedback mechanism by FSH and LH and by the sex hormones that are released from the gonads in response to them (estrogens, progesterone and testosterone). Release of GnRH starts at puberty Inhibitors: Stress and Prolactin (possibly inhibits their effects at the level of the ovary) Dr_ Salah AL-shuaiby  Actions - Trophic effect on the gonads: Increase vascularity, cellularity and secretion of sex hormones from the gonads in both males and females. - Control of gonadal functions: production of sperms in males and the menstrual cycle including ovulation in females (see the reproductive system). Dr_ Salah AL-shuaiby  PITUITARY INSUFFICIENCY (PAN-HYPOPITUITARISM) Causes: Tumors (e.g. craniopharyngioma or pituitary tumors) Surgical removal of the pituitary (for eradication of a tumor) Sheehan’s syndrome (pituitary infarction following postpartum hemorrhage, due to severe vasoconstriction as a body response to shock) - Infiltration of the pituitary (e.g. by iron as in hemochromatosis) - Infections (e.g. tuberculosis or meningitis). Features: - (Combined features of hupothyroidism, Addison’s disease, hypogonadism & low GH). - Skin pallor due to loss of the melanocyte stimulating activity of ACTH. o Intolerance to cold due to decreased rate of metabolism caused by low TSH GH & ACTH. o Loss of menstrual cycle in females due to low LH & FSH. o Failure of lactation due to low prolactin. 0 Hypoglycemia & increased sensitivity to insulin (due to low GH & ACTH which antagonize insulin).  Features 0 Hypopituitarism improves diabetes mellitus. - Increased sensitivity to stress (due to lowACTH) 0 Atrophy of some endocrine glands (e.g. gonads & adrenal cortex (zona fasciculata & zona reticularis, but not zona glomerulosa) 0 Polyuria due to absence of ADH; However, this is not very severe because the decreased metabolism is associated with decrease in the osmotic load that should be excreted. Dr_ Salah AL-shuaiby Posterior pituitary gland Dr. Salah Al-shuaiby (assistant professor ) 2024  Posterior pituitary gland The posterior pituitary gland is composed mainly of glial-like cells called pituicytes. Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH). Secretions of the posterior pituitary are controlled by nervous signals from hypothalamus (under hypothalamic control) The synthesized hormones in the cell bodies are transported along the (hypothalamic hypophyseal tract) in combination with “carrier” proteins called neurophysins down to the nerve endings in the posterior pituitary gland. (stored). Dr_ Salah AL-shuaiby  Posterior pituitary hormones 1- Antidiuretic Hormone (ADH). Synthesis: Synthesized as pre-prohormone a nonapeptide (nine amino acids) in the cell bodies of hypothalamic supraoptic nucleus. At the nerve termini the secretory granules containing the mature hormone and its associated neurophysin are stored until a subpopulation of neurons is stimulated to release its contents into the adjacent capillaries for transport into the general circulation. Dr_ Salah AL-shuaiby  Receptors for ADH Receptors for ADH (3 types): 1. V1A 2. V1B 3. V2 V1A : mediate vasoconstriction (blood vessels) – also in liver glycogenolysis. V1B :are unique to anterior pituitary mediate increased ACTH secretion. V2: are located in the principle cells of distal convoluted tubule and collecting ducts in kidney.  Mechanism of action of ADH -ADH binds to V2 receptors on the peritubular (serosal) surface principal cells of the distal convoluted tubules and medullary collecting duct.(Serosal means near the blood vessel not the lumen). After the hormone binds to the receptor it stimulates the production of secondary messenger (adenylate cyclase) which will stimulate the conversion of ATP to cAMP. Once cAMP is formed it will activates protein kinase A leading to phosphorylation of some proteins that will cause production and insertion (movement) of aquaporin2 (channels for water absorption) into the luminal membrane and open pores to allow water to be reabsorbed from the tubules back to the blood. By this action it enhances the permeability of the collecting tubules to water only. Increased membrane permeability to water permits back diffusion of solute-free water, resulting in increased urine osmolality (concentrates urine). (Means that it will lead to production of concentrated urine and prevent water loss). When ADH is removed, the water channels withdraw from the membrane and the Dr_ Salah AL-shuaiby Dr_ Salah AL-shuaiby  Osmotic Stimuli of ADH Stimuli: increase plasma solutes (Na+) will lead to↑ in plasma osmolality which will stimulates both ADH release and thirst via: Receptors: osmoreceptors in or near the hypothalamus. Sensitivity: changes of 1-2% → ↑ ADH secretion, so it’s very sensitive to changes in osmolality. Effect: ADH secretion is very sensitive to changes in osmolality by (osmoreceptors). Fasting or dehydration → increase plasma osmolality (salt > water) → osmoreceptors (in brain) sense that → shrinking → membrane action potential from hypothalamus → reach posterior pituitary and thirst center → ADH released and drinking water → decrease osmotic pressure.. ↑ Osmotic pressure/osmolality → ↑ ADH secretion. ↓ Osmotic pressure/osmolality → ↓ ADH secretion. Dr_ Salah AL-shuaiby  Non-osmotic stimuli:Volume effects Stimuli: low blood volume (hypovolemia) & low blood pressure. Receptors: baroreceptors in carotid artery & aortic arch (pressure receptors) mediated by vagus Nerve + stretch receptors in left atrium and pulmonary veins. Normally: pressure receptors tonically inhibit ADH release. Sensitivity: senses changes 15 - 25% in volume → ↑ ADH secretion,sensitivity to baroreceptors is less than osmoreceptor. Effect: ↑ blood pressure or ↑ blood volume → ↓ ADH secretion. ↓ blood pressure or ↓ blood volume → ↓ neural input from baroreceptors (pressure receptors) → relieves the source of tonic inhibition on hypothalamic cells → ↑ ADH secretion. Dr_ Salah AL-shuaiby  Non-osmotic stimuli:Others Stimuli that increase ADH secretion (Physiological Stress): - Pain, nausea, trauma, surgical stress, emotional stress and fear. Stimuli that decrease ADH secretion: - Alcohol intake (they lose their ability to control urination → urinate on themselves due to decreased ADH) Dr_ Salah AL-shuaiby  ADH Disorders ADH deficiency: “diabetes insipidus” A disorder resulting from deficiency of ADH or its action. Characterized by: passage of copious amounts of dilute urine. (a urine that has a lot of water and little electrolytes). 1- Neurogenic (central): failure of hypothalamus or neurohypophysis to synthesize or secrete ADH. (The amount of ADH is abnormal, but the receptors are intact) It can be treated by synthetic ADH (desmopressin “DDAVP”) given by nasal inhalation. 2- Nephrogenic: failure of the kidney to respond appropriately to ADH. When the renal tubules of the kidney fail to respond to circulating ADH. (The amount of ADH is normal, but it’s unable to act on the receptors) If you have increase ADH= nephrogenic If you have decrease ADH/ neurogenic Dr_ Salah AL-shuaiby  2-Oxytocin Function of Oxytocin: A) Breast feeding Oxytocin triggers milk ejection (“letdown” reflex) (or milk ejection reflex). Contracts the myoepithelial cells of the alveoli. Mechanosensory information from the nipple reaches the magnicellular neurons, causing the release of oxytocin into the general circulation. Oxytocin acts on receptors on myoepithelial cells in the mammary gland acini leading to the release of milk into the ductal system and, ultimately, the release of milk from the mammary gland. Contracts the myoepithelial cells of the alveoli (classic neuroendocrine reflex). Dr_ Salah AL-shuaiby  Function of oxytocin B) Childbirth (parturition) In late pregnancy, uterine smooth muscle (myometrium) becomes sensitive to oxytocin (positive feedback) Oxytocin is a strong stimulant of uterine contraction. Regulated by a positive feedback mechanism This leads to increased intensity of uterine contractions, ending in birth. oxytocin use in clinical, in the third stage of delivery: when the head of the baby come out give the patient injection of oxytocin help her in contraction. C) Ejaculation In males secretion increases at time of ejaculation (contraction of smooth muscle of vas deferens) Dr_ Salah AL-shuaiby  Regulation of oxytocin Stimulate secretion: In Both Sexes: 1. Hugging, touching & orgasm. 2. Stress. In female: 1. Sounds of baby cry. 2. During delivery when the head of the baby reaches the cervix. In male:Contraction of smooth muscle of vas deferens(ejaculation). Inhibit secretion: In Both Sexes: Alcohol. Dr_ Salah AL-shuaiby Physiology of Thyroid Gland Dr. Salah Al-shuaiby (Assistant Professor ) 2024  Thyroid gland * The first recognized endocrine gland. * It is located below the larynx on either sides and anterior to the trachea. - It consists of two lobes that are connected by the thyroid isthmus. * 20g in adult. - Concerning its histology, it is made up of multiple acini (or follicles). Each follicle is surrounded by a single layer of cells and filled witha protein material (known as the colloid). - The type of protein in the colloid is known as the thyroglobulin. Hormones : T4 (tetraiodothyronine) (thyroxine) 90%. T3 (Triiodothyronine)10%. - T4 is the major product. - T3 is the most active form. Dr_ Salah AL-shuaiby Thyroid Hormones [T3 - T4] synthesis Biosynthesis: by the follicular cells. Steps in biosynthesis :- 1- Thyroglobulin formation and transport: - Glycoprotein. - Combined of 140 Tyrosine that happened in Rough endoplasmic reticulum and Golgi apparatus. 2- Iodide pump or iodide trap: - Active transport (because the concentration in thyroid is more than in blood) - It is stimulated by TSH. 3- Oxidation of iodide to iodine : BY Thyroid peroxidase. - It is located in or attached to the apical membrane. 4- Organification (iodination) of thyroglobulin : - Binding of iodine with thyroglobulin. - Catalyzed by thyroid peroxidase, to form - Remain attached to thyroglobulin until the gland stimulated to secret. *MIT: mono iodo tyrosine & *DIT: di iodo tyrosine Dr_ Salah AL-shuaiby  Thyroid Hormones [T3 - T4] synthesis 5- COUPLING REACTION: DIT + DIT T4 (faster) (= 35% ) DIT + MIT T3 (= 7%) Uncoupled residues “MIT & DIT” (= 56% ) - Catalyzed by thyroid peroxidase. - It is stored as colloid in lumen. - Is sufficient for 2-3 months. 6- Endocytosis of thyroglobulin to intracellular. 7- Fusion of lysosomes immediately with the vesicles. 8- Hydrolysis of the peptide bond to release DIT+MIT+T4+T3 from the thyroglobulin. 9- Delivery of T4 and T3 to the systemic circulation. 10- Deiodination of DIT and MIT by thyroid deiodinase (recycling). Dr_ Salah AL-shuaiby Thyroid Hormones in The Circulation  RELEASE OF T4&T3 TO THE TISSUES 1)The release is slow because of the high affinity of the plasma binding proteins. - ½ of T4 in the blood is released every 6 days. - ½ of T3 in the blood is released every one day. 2) T4 & T3 readily diffuse through the cell membrane. 3) Stored in the targeted tissues (days to weeks). 4) Most of T4 is deionized to T3 by iodinase enzyme. T3 is in blood is much smaller amounts but, is 4 times as potent as T4. 5) In the nucleus, T3 mainly binds to “thyroid hormone receptor” and influence transcription of genes. Dr_ Salah AL-shuaiby Action of Thyroid Hormones Dr_ Salah AL-shuaiby Action of Thyroid Hormones cont.. Dr_ Salah AL-shuaiby Regulation of thyroid HormonesSecretion It is regulated by the hypothalamic-pituitary axis. 1. Hypothalamic control: TRH → ↑ TSH. 2. Pituitary control: TSH→ ↑ T3 & T4. 3. Somatostatin [GHIH] → ↓ TSH. 4. Negative feed back control: ↑ T3 &T4 in the blood → ↓ TSH. 5. Iodine supply: -chronic ↓ Iodine in the diet→ hypothyroidism. - acute ↓ Iodine in the diet→ hyperthyroidism. Dr_ Salah AL-shuaiby Disease of The Thyroid Gland Dr_ Salah AL-shuaiby Hyperthyroidism & Hypothyroidism Dr_ Salah AL-shuaiby  Parathyroid Gland & Calcium Homeostasis Dr. Salah Al-shuaiby M.B.B.S , MSc in medical physiology, MD.Diagnostic Radiology (assistant professor ) 2024  Distribution of Calcium in Body - 0.1% in ECF - 0.99 % in ICF “ endoplasmic reticulum “ - 99% in skeleton and teeth (Bones) - we are going to talk about the calcium which is exist in the plasma (ECF) Total conc of calcium in ECF=10 mg/dl ,2.5mmol/L plasma calcium is distribution in 3 forms: 1- calcium bond to protein 41% ( since it's bind to protein it's not diffusible). 2- calcium complexed to anions 9% ( diffusible). 3- ionized calcium 50% ( free ) ( responsible for nerve and muscle action potentials). * any increase in complexed calcium will affect the level of ionized calcium. ( ionized calcium will decrease). * if there is decrease in Ca level this will increase the influx of Na and will cause spontaneous action potentials. Dr_ Salah AL-shuaiby  Bone Composition - Organic Matrix (Tensile Force)(30%): 1. Collagen Fibers → 95% 2. Ground Substance: ECF and Proteoglycans → 5% - Bone Salts (Compressional Force)(70%): 1. Salts of Calcium and Phosphate in the form of Hydroxyapatite crystals Ca10(PO4)6(OH)2→ 99% 2. Mg, Na, K, Carbonate ions. 3. Amorphous salts: exchangeable calcium that plays a role in the rapid regulation of ionized Calcium level in ECF. Always in equilibrium with Calcium in ECF. 0.4-1% of total bone Ca2+ so that when calcium level drops, these salts can quickly re-establish equilibrium. Osteocytes are provided with pumps to move this calcium.. Dr_ Salah AL-shuaiby  Calcium & phosphate Ca × P = constant Approximately 85 % of the body’s phosphate is stored in bones,14-15 % is in the cells. Only Less than 1% is in the extracellular fluid. Although extracellular fluid phosphate con. is not nearly as well regulated as calcium concentration, phosphate serves several important functions and is controlled by many of the same factors that regulate calcium. Phosphorous is an essential mineral necessary for ATP and cAMP second messenger systems Phosphate plasma concentration is around 4 mg/dL. Forms: - Ionized (diffusible) around 50% of total - un-ionized (non-diffusible) protein- bound (50%) Dr_ Salah AL-shuaiby  Calcium Physiology Physiological importance of Calcium: 1-Calcium salts in bone provide structural integrity of the skeleton.(support) 2-Calcium ions in extracellular and cellular fluids is essential to normal function for the biochemical processes such as: Neuromuscular excitability. Hormonal secretion. Enzymatic regulation. Blood coagulation. When we took a blood sample and put it in a tube it will coagulate but calcium function here is to prevent the coagulation. Second messenger. It helps also in muscle contraction. ^ all of these functions are done by ionized calcium. Dr_ Salah AL-shuaiby  Calcium metabolism Normal calcium intake from diet is 1000mg/day, vitamin D promotes the absorption of about 35% of calcium (around 350mg/daily) the remaining is unabsorbed and excreted in the feces. (650mg/day). An additional 250 mg/day of calcium enters the intestines via secreted gastrointestinal juices and sloughed mucosal cells. Thus, about 90% (900 mg/day) of the daily intake of calcium is excreted in the feces + excretion (urine 100) equals the intake (1000). At the level of the bone there will be always equilibrium between deposition and absorption.. If there someone needs more calcium, what will happen? There will be increase in absorption at the level of the intestine and kidneys or decrease excretion of calcium‫ز‬ Dr_ Salah AL-shuaiby  Regulation of Calcium Level -Non-Hormonal mechanisms: Can rapidly buffer small changes in plasma concentrations of free Calcium. - Hormonal mechanisms: Provide high-capacity, long-term regulation of plasma Calcium and Phosphate concentrations. Hormones Vitamin D (Diet and sun) Parathyroid hormone. (Parathyroid gland) Calcitonin Thyroid gland - [Ca2+] < 9-10.5 mg/dl → Tetany + seizures + excitation of the nervous system. - [Ca2+] > 9-10.5 mg/dl → Renal stones + depression of the nervous system. Hormones that regulate Ca++ Dr_ Salah AL-shuaiby Parathyroid hormone Dr_ Salah AL-shuaiby Functions of Parathyroid hormone Dr_ Salah AL-shuaiby Hormones that regulate Ca++(PTH) Dr_ Salah AL-shuaiby Hormones that regulate Ca++) Calcitonin( Dr_ Salah AL-shuaiby Functions of Calcitonin Dr_ Salah AL-shuaiby )Calcitonin( Dr_ Salah AL-shuaiby Hormones that regulate Ca++) Vitamin D( Vitamin D is a prohormone that must undergo two successive hydroxylation reactions to become the active form known as 1,25-dihydroxy vitamin D or calcitriol. - It is formed in the skin from (7- dehydrocholesterol) by Ultraviolet B light. - Then stored in the liver. - Converted in the liver to 25- Hydroxycholecalciferol - Feedback control limits concentration. - Converted to the active form in the kidney: (parathyroid hormone (PTH) stimulates 1α hydroxylase which makes 1,25- Dihydroxycholecalciferol (calcitriol) - Under the feedback control of (PTH). Dr_ Salah AL-shuaiby )Vitamin D( actions Dr_ Salah AL-shuaiby Dr_ Salah AL-shuaiby Abnormalities of PTH Dr_ Salah AL-shuaiby Signs of hypoparathyroidism:Hypocalcemia Dr_ Salah AL-shuaiby Physiology of Pancreas & Insulin Dr. Salah Al-shuaiby M.B.B.S , MSc in medical physiology, MD.Diagnostic Radiology (Assistant Professor ) 2025  Pancreas A triangular gland, which has both exocrine and endocrine cells, located behind the stomach. - Acinar cells produce an enzyme-rich juice used for digestion (exocrine product). - Pancreatic islets (islets of Langerhans) produce hormones involved in regulating fuel storage and use (endocrine product).. Cells of Islets Of Langerhans : - 1-2 million islets. - Beta (β) cells produce insulin (70%). - Alpha (α) cells produce glucagon (20%). - Delta (δ) cells produce somatostatin (5%). - F (PP) cells produce pancreatic polypeptide (5%). - G cells produce gastrin (1%),  Insulin Secreted by β cells in response to elevated blood glucose. Functions: Increases transport of glucose to skeletal muscle, liver and adipose tissue (lowers blood glucose levels). The ONLY metabolically active hormone capable of lowering blood glucose levels. Every other metabolically active hormone causes hyperglycemia except Insulin. Degraded within the liver, kidneys, muscles, and less in most of other tissues. 80% metabolized in the liver. Half-life of about 5-6 minutes. Glucose Transporters (facilitated diffusion): Factors controlling insulin secretion. Mechanism of glucose stimulation of insulin Secretion 1. Glucose enters through GLUT-2 (insulin-independent) into the beta cells of pancreas, this way beta cells function as glucose-sensing cells. 2. This glucose is used for ATP synthesis 3. The ATP is used to close KATP channels which traps more potassium inside the cells and help the cells reach the voltage needed to open voltage-gated calcium channels. 4. Calcium enters the cells, which acts as a key to stimulate exocytosis and release of insulin. Regulation Of Insulin Secretions Physiological roles of insulin Physiological roles of insulin  Glucagon Hormone secreted by Alpha cells of the islets of Langerhans, in the lower gastrointestinal tract, and in the brain. A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent. Secreted When blood glucose concentration falls (skipping meals, fasting), Glucagon has several functions that are opposed to those of insulin. Like insulin, glucagon is a large polypeptide. Regulation Of glucagon Secretions Physiological roles of glucagon Diabetes mellitus  Types of Diabetes Diabetes Mellitus Type I insulin dependent (Autoimmune attack) (10%) Mainly affects children. Cause : Immune-mediated selective destruction of β cells, leading to: Hyposecretion of insulin. Management and Treatment: Insulin dependent, so the treatment is: Insulin Injection. Diabetes Mellitus Type II (90%-95%) More common in some ethnic groups. - Late onset, genetic and family related risk factors. - In most cases, onset of type 2 diabetes occurs after age 30 years, often between the ages of 50 and 60 years, and the disease develops gradually. Therefore, this syndrome is often referred to as adult- onset diabetes. Cause: - Unhealthy foods and inactive lifestyles with sedentary behaviour - Resistance of body cells to insulin keeps blood glucose too high Management and Treatment: - Lifestyle modification with physical activity and/or healthy diet - Diet and oral hypoglycemic agents Summary of the effects of DM Adrenocortical Hormones Dr. Salah Al-shuaiby (Assistant Professor ) 2025  Adrenal Gland There are two adrenal (suprarenal) glands that lie at the superior pole of the two kidneys. ❖ Paired, small pyramidal-shaped organ atop the kidneys. ❖ Weigh 4/6-10 g. ❖ Structurally and functionally, Divide into two morphologically and distance regions they are two glands in one : Adrenal cortex, Adrenal medulla. Dr. Salah Al-shuaiby Dr.Salah AL-SHUAIBY  Adrenal Cortex ❖ 80%-90% glandular tissue derived from embryonic mesoderm. ❖ Synthesizes and releases/Secrete group of steroid hormones called corticosteroids. ❖ All synthesized from the steroid cholesterol. ❖ Have different functions. ❖ Different corticosteroids are produced in each of the three layers. Dr.Salah AL-SHUAIBY  Synthesis Of Steroid Hormones Steroids are derivatives of cholesterol. Cholesterol is from the lipid droplets in cortical cells (cholesterol esters in LDL) Steroidogenic Acute regulatory protein (StAR protein) transfers cholesterol to the inner membrane of the mitochondria. steroid hormones are synthesized and secreted on demand (not stored) e.g.Aldosterone. The first step in the synthesis of all steroid hormones is conversion of cholesterol to pregnenolone by the enzyme cholesterol desmolase. Newly synthesized steroid hormones are rapidly secreted from the cell. Following secretion, all steroids bind to some extent to plasma proteins: CBG (transcortin) and albumin. Dr.Salah AL-SHUAIBY Synthesis Of Steroid Hormones  Main Glucocorticoids in Humans Cortisol: Very potent. Account for 95% of glucocorticoid activity. Corticosterone: Account for about 4% of total glucocorticoid activity. Less potent than cortisol. Cortisol: Corticosterone: Produced in humans in a ratio of 10:1 Glucocorticoids Produced by the fasciculata and reticularis layers of the adrenal cortex. Glucocorticoids (cortisol): recognized early to increase plasma glucose levels: ○ Mobilization of amino acids from proteins. ○ Enhance liver gluconeogenesis. Target tissues: most body tissues Dr.Salah AL-SHUAIBY  Regulation of Glucocorticoid Secretion CRH from hypothalamus is the major regulator of ACTH secretion. ADH is also secretagogue for ACTH. ACTH from anterior pituitary stimulates cortisol synthesis and secretion. CRH (and ACTH) are secreted in pulses. The greatest ACTH secretory activity occurs in the early morning hours and diminish late in the afternoon. Cortisol has a direct negative feedback effect on both the hypothalamus and ant. pituitary. Dr.Salah AL-SHUAIBY Actions of Glucocorticoids Dr.Salah AL-SHUAIBY Actions of Glucocorticoids Dr.Salah AL-SHUAIBY  Cushing’s Syndrome Cushing’s syndrome results from continued high glucocorticoid levels. When Cushing's syndrome is secondary to increased ACTH secretion by the anterior pituitary: Cushing's disease, when it is from any other source it is called Cushing’s syndrome. Onset 3rd - 6th decade, 4:1 females: Males. Causes 1. Adenomas of the anterior pituitary → Increased ACTH. 2. Abnormal function of the hypothalamus → increased CRH. 3. Ectopic secretion of ACTH by a tumor elsewhere in the body, such as an abdominal carcinoma. 4. Adenomas or carcinoma of the adrenal cortex. 5. Pharmacologic: Cushing's syndrome may occur when large amounts of glucocorticoids are administered over prolonged periods for therapeutic purposes. (Chronic inflammatory states like rheumatoid arthritis) Dr.Salah AL-SHUAIBY Cushing’s Syndrome Dr.Salah AL-SHUAIBY Cushing’s Syndrome Dr.Salah AL-SHUAIBY