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Endocrinology

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Published in: Biology | Physiology
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Introduction to Endocrinology

Subhamoy M / Kolkata

10 years of teaching experience

Qualification: M.Sc (Presidency College - 2011), B.Sc (Surendranath College - 2009), B.Ed (WBUTTEPA - 2019)

Teaches: Biology, Botany, Physiology, Zoology, Bio-medical, Food & Nutrition, Medical Entrance Exams, NEET

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  1. PHYSIOLOGY: Introduction to Endocrinology CHEMICAL MESSENGER SYSTEMS: 3. TYROSINE DERIVATIVES (AMINES) secreted by • Adrenal medulla (epinephrine and norepinephrine) 1. 2. 3. 4. 5. 6. NEUROTRANSMITTERS - released by triiodothyronine and T4 tyroxine) on their axon terminals and act locally to affect nerve cell fxns. ENDOCRINE HORMONES - produced by glands and released into the bloodstream to act on cells from a distance and have longer lasting effects. NEUROENDOCRINES - released by neurons and released into the bloodstream to act on cells in another location. PARACRINES released by cells into the interstitial fluid to act on cells surrounding it. AUTOCRINES released by cells into the interstitial fluid and influence activity same cell responsible for its production by interacting with receptors bound to its membrane. CYTOKINES - released into the ECF and may function as paracrine, autocrine, or endocrine. • Lymphokines and interleukins — released by helper cells and act on the cells of the immune system. • The different messenger systems of the body interact with one another to maintain homeostasis. Example: o Neuroendocrine cells from the hypothalamus release their neurohormones including ADH oxytocin and hypophysiotropic hormones which stimulate the release of anterior pituitary hormones (endocrine) o Adrenal medullae and pituitary gland function in response to neural stimulation. • Endocrine hormones are carried by the circulatory system and may affect multiple types of cells or only a specific type of cell which has the receptor for that hormone. ovarian hormones and adrenocorticotropic hormone) CHEMICAL STRUCTURES HORMONES: and SYNTHESIS of 1. 2. PROTEINS AND PEPTIDE HORMONES: , Proteins 100 amino acids • Synthesized as large preprohormones in the rough ER and then later cleaved to become prohormones which are biologically inactive • Transferred into the Golgi apparatus and packed into vesicles containing enzymes that cleave the prohormones into smaller more active forms. • Vesicles are stored in the cytoplasm and usually bind to the cell membrane. Exocytosis occurs as the vesicles fuse with the cell membrane. Stimulus for exocytosis include: o Increased intracellular CA++ due to depolarization of the cell membrane o Increased cAMP due to stimulation of the cell via receptors on its surface. • Proteins are water soluble hence they may be released into the bloodstream. STEROIDS • Synthesized from cholesterol. They are lipid-soluble which allows them to simply diffuse out of the cell (i.e. exocytosis is not needed for their release) and hence are not stored. • Cholesterol needed for its synthesis is either stored as cholesteryl esters in vacuoles or synthesized by steroid producing cells. Most of cholesterol utilized however, is found in PROTEINS AND POLYPEPTIDES - comprises most of the bodies hormones and include: Anterior and posterior pituitary hormones • Pancreas (insulin and glucagons) , Parathyroid (PTH) , others STEROIDS - secreted by: • Adrenal cortex (cortisol and aldosterone) • Ovaries (estrogen and progesterone) Testes (testosterone) Placenta (estrogen and progesterone) the plasma. TYROSINE-DERIVED (AMINES) HORMONES • Formed by action of cytosolic enzymes. • Thyroid hormones:
  2. o Incorporated into thyroglobulin before it is • Metabolic destruction by cells stored, and is released once cleaved from • Binding to tissues the polypeptide • Excretion by the liver into bile o Once in the blood, it binds to plasma • Excretion by the kidneys into the urine proteins, especially thyroxine binding globulin o Clearance by endocytosis • Hormone-receptor complexes in the cell Adrenal medullary hormones (catecholamines): membranes are endocytosed. 0 4x more epinephrine are secreted than • Receptors are recycled back into the membrane while hormones are metabolized norepinephrine. o Stored in preformed vessels and released within the cell. via exocytosis o May exist as plasma in conjugated or fcéå/ater-soluble hormones are rapidly metabolized by form. CLEARANCE the blood and tissues then excreted by the urine or liver. o Protein-bound hormones take longer to be metabolized. Hormones have varying onset and duration of activity. o Norepinephrine and epinephrine are secreted within seconds after stimulation of the glands and may exert their actions still within seconds. o Growth hormones and thyroxine may require months before they take full effect. Concentrations and hence, secretion are in very low amounts. , FEEDBACK CONTROL: o Negative feedback — variable controlled is the activity of the target tissue. o Positive feedback — results to surges in hormone levels. (example: LH influence release of estrogen, which will in itself trigger the release of more LH from pituitary gland) o Cyclical variations may result from level of activity of neural pathways involved in controlling hormone release. (example: growth hormone is released mostly during the first hours of sleep and less in the later stages of sleep) , TRANSPORT: o Water soluble hormones (proteins, peptides and catecholamines) are dissolved in the blood and easily diffuse through the capillaries into the ISF and ultimately into their target cells. o Steroids (derived from cholesterol and hence are lipid soluble) and thyroid hormones are bound to plasma proteins, and therefore are incapable of diffusing through the capillaries. As a result, they remain inactive while bound to the plasma proteins. , CLEARANCE: o Metabolic clearance rate = Rate of disappearance of hormone from the plasma/Concentration of hormone in each milliliter of plasma o Hormones may be cleared from the blood by: MECHANISM OF ACTION OF HORMONES , LOCATIONS OF RECEPTORS: o In or on the cell membrane peptide and catecholamines o In the cytosol — steroid hormones protein, o In the nucleus — thyroid hormones • Regulation of receptors affect the sensitivity of target cell to the hormone. o Down regulation results from the decrease in number of the receptors, and hence, to a decreased sensitivity to a particular hormone. This may be due to: • Inactivation of some receptor molecules • Decrease in intracellular signaling proteins (cAMP?) • Internalization (endocytosis) of receptors • Lysosomal degradation after internalization • Decreased production of receptors o Up regulation results to increased sensitivity to a hormone. , TYPES OF RECEPTORS: o Ion channel-linked receptors Neurotransmitters Causes opening/closing of ion channels Effects are a result of influx/efflux of ions o G-protein linked receptors Have seven segments; intracellular segment is bound to G-protein G- PROTEIN - has three parts (trimeric); alpha, beta, gamma subunits. named for their ability to bind guanosine nucleotides. In
  3. inactive state GDP is bound to• Activation of receptor by hormone allows alpha subunit. binding of G-protein to receptor. - May either be stimulatory (Gs)• GS will stimulate adenylyl cyclase which will or inhibitory (Gi) convert intracellular ATP to cAMP. • cAMP activates cAMP-dependent protein • Activation of receptor causes GDP- kinase which will phosphorylate specific bound trimeric G-protein to associate intracellular proteins, leading to the cell's with receptor and exchange GDP for response. GTP. • Gi inhibits adenylyl cyclase and, consequently, GTP causes alpha subunit to dissociate cAMP formation. from remaining subunits and instead• cAMP usually activates a cascade of enzymes binds to other intracellular proteins (i.e. activation of one enzyme leads to activation which would either activate ion of a second one and so forth), hence a small channels or intracellular enzymes. amount elicits a response of great magnitude. • Alpha subunit inactivates itself by converting its GTP to GDP and bindingCeII membrane phospholipids second messenger once again with beta and gammasystem subunits. • Stimulation of transmembrane receptor activates phospholipase C, which breaks down • Activation of receptor have two possible membrane phospholipids,especially phosphatidylinositol bisphosphate (PIP2) into either diacylglycerol (DAG) or inositol opening of ion-channels triphosphate (IP3). 2. activation of intracellular enzymes o Enzyme-linked receptors • Pass through membrane only once in contrast to G protein-linked receptors • Most have intrinsic enzymatic activity. However, there are a few that rely on their associated enzymes for altering cell function. • Example: Leptin released by adipose cells that act through JAK2 and STAT. • Example: transmembrane receptor which, when activated, becomes adenylyl cyclase (a membrane bound enzyme) that catalyzes formation of cAMP, a second messenger. o Intracellular receptors • For lipid soluble vitamins that easily passes through the cell membrane to reach receptors in the cytosol or nucleus. (steroid and thyroid hormones, vitamin D, retinoid hormone) • Hormone-receptor complex binds to a promoter region (hormone response element) in the DNA and either inhibits or promotes the formation of mRNA. • Influence on mRNA allows their effects to last for days. , SECOND MESSENGER MECHANISMS o Important second messenger mechanisms: • calcium ions associated with calmodulin • products of breakdown o Adenylyl cyclase system membrane phospholipids — cAMP second messenger DAG — activates phosphokinase C which in turn activates intracellular proteins leading to cell's reponse INOSITOL TRIPHOSPHATE - mobilizes calcium ions from mitochondria and ER. (Calcium ions exert their own effects on the cell.) o Calcium-calmodulin 2nd messenger system • Operates in response to influx of calcium into the cell as a result of: 1. changes in cell membrane potential that opens calcium channels 2. binding of hormones to receptors that open calcium channels • Calcium binds to calmodulin upon entering the cell. • Calmodulin has four sites and is activated when three or all four sites are bound to calcium. • Activated calmodulin then activates calmodulin-dependent protein kinases, which in turn activates intracellular proteins that are responsible for the cell's response to the hormone. HORMONES ACTING DIRECTLY ON GENETIC MACHINERY OF THE CELL • Steroids increase protein synthesis • Steroids diffuse through the cell membrane (since they are cholesterol derived and hence lipid soluble) and into the cytosol where their receptors are found.
  4. • Sequence of events unfolds as mentioned earlier regarding intracellular receptors. Thyroid hormones increase gene transcription • Receptor proteins are in the nucleus itself (intranuclear receptors), in contrast to intracellular receptors of the steroid hormones. • Their effect may last for days or longer.

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