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Endocrinology Review.doc

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McGill University
PHGY 210
Ann Wechsler

ENDOCRINOLOGY REVIEW Endocrine signalling: - Involves hormone secretion into the blood by endocrine gland. - To hormone is transported by the blood to a distant target site. - Example of long-distant signalling: o The anterior pituitary gland releases LH and FSH which are transported to the gonads (target site) through the blood vessels. The gonads then release steroid hormones (estrogens in females and androgens in males) Neuroendrocrine signalling: - Involves release of neurohormones from neurones. - These travel to a non-neuronal tissue and elicit hormonal response. Short-distance signalling: - Paracrine signalling: o Ex: parathyroid hormone related peptide is a paracrine signalling hormone - Autocrine signalling: o Ex: cancer cells release factors that tell the cells to divide. Six steps of hormonal communication: 1. Synthesis of the hormone or neurohormone by endocrine cells or neurones. 2. Release of the hormone or neurohormone 3. Transport of the hormone or neurohormone to the target site by the blood stream 4. Detection of the hormone or neurohormone by a specific receptor protein on the target cells 5. Change in cellular metabolism triggered by the hormone-receptor interaction 6. Removal of the hormone, which often terminates the cellular response (often through negative feedback loops) o Many of these steps are site of regulation that allows the control of hormonal communication. o Steps 4 and 5 are universal. They are absolutely necessary for proper communication to occur. o Certain dietary substances also function as hormonal signalling molecules. Classical endocrine organs: - Hypothalamus - Anterior pituitary gland - Posterior pituitary gland - Thyroid gland - Parathyroid gland - Heart (release of atrial natriuretic peptides) - Adrenal glands: cortex and medulla - Pancreas: islets of Langerhans - Gonads o Ovaries in female o Testis in male Hypothalamic-pituitary signalling: - Via blood vessels of the pituitary stalk 1 - Hypothalamic-hypohyseal Portal System: from the hypothalamus to the adenohypohysis. - Hypothalamic neurohormones act on one of the six types of hormone-producing cells in the anterior pituitary. - They can be of two types: o Releasing hormones/factors o Inhibiting hormones/factors Classes of hormones based on their structures: Tells nothing about physiology and receptors (except for steroids) - Glycoproteins: o Polypeptides with sugars attached to their surface - Polypeptides: o Usually small - Steroids: o Very small o Vitamin D is a metabolite of steroids o Lipohilic molecules. They can get in the cell on their own by passing through the phospholipids bilayer and then act on the nuclear receptors in the cytoplasm or in the nucleus. o All steroid hormones are structurally very similar. They all have a common core of four rings. - Amines: o Very small Synthesis of protein hormones - Any hormone that is a protein in nature is encoded by one or many genes. - Synthesis of preprohormones is done on ribosomes attached to the rough ER. - They are then processed in the ER to become prohormones. - They then pass through the Golgi apparatus and are packaged into secretory vesicles for release. Structures of thyroid hormones: 1. T4 has four iodine groups 2. T3 has three iodine groups 3. If you lack thyroid hormones, you end up short and dumb (dwarfism and cretinism) Properties of hormone receptors: 1. Specificity: recognition of single hormone or hormone family. 2. Affinity: high affinity for a hormone = binding hormone at its physiological level. 3. Saturability: finite number of receptors 4. Measurable biological effect: measurable biological response due to the interaction of hormone with its receptor. Receptor regulation: 2 Receptors can be upregulated either by increasing their activity in response to hormone or their synthesis. Receptors can be downregulated either by decreasing their activity or their synthesis. Mechanisms by which a hormone can exert effects on target cells: 1. Direct effects on function at the cell membrane: Usually through series of phosphorylation 2. Intracellular effect mediated by second messenger systems: Ex: G-protein coupling 3. Intracellular effects mediated by genomic or nuclear action Influences expression of a subset of genes Effect on nuclear receptors Feedback control of hormone secretion: - Secreted hormones are precisely regulated by feedback mechanisms - Regulation may be mediated by either hormonal or non-hormonal mechanisms - Non-hormonal feedback is not conceptually different from hormonal feedback - Note: o CRH = corticotropin releasing hormone o ACTH = adrenocorticotropic hormone o Cortisol is a glucocorticoid The pituitary Gland: Anatomy Located under the hypothalamus Two distinctly different tissues: 1. Adenohypophysis (anterior pituitary or pars distalis) endocrine tissue 2. Neurohypophysis (posterior pituitary or pars nervosa) neural tissue Signalling between the hypothalamus and the pituitary: o The hypothalamus is a rich source of hormones o Can have two effects: increase or release of hormones in the pituitary gland. Posterior Pituitary Gland: o Outgrowth of the hypothalamus connected by the pituitary stalk. o Prehormones processed in secretory granules during axonal transport. o Mature hormones liberated from the carrier molecules , neurophysins. Hormones Hypothalamic hormones secreted o Most are peptides in nature o Arginine vasopressin (ADH) and oxytocin differ only by two a.a. They are evolutionary products of a gene duplication. ADH controls blood pressure, while oxytocin controls uterine contractions and lactation. o Dopamine is a prolactin-inhibiting hormone (PIH). o Thyrotropin releasing hormone (TRH) is formed of only 3 a.a. 3 o Somatostatin possesses a disulfide bond. Posterior pituitary: o Oxytocin o Vasopressin (ADH): Secretion increased when body needs water Two receptors, V1 and V2 V1 receptors mainly on smooth muscle cells surrounding blood vessels o Both synthesized in hypothalamus, but secreted in posterior pituitary. o Circulating half-lives 1-3 minutes Effects Vasopressin: o Increase blood pressure Oxytocin: o Uterine contractions o Lactation Mechanism of Vasopressin: interaction with V1 receptors stimulates phospholipases action o Increased formation of inositol triphosphate o Stimulates the mobilization of calcium from endoplasmic reticulum o Increased muscular contraction and vasoconstriction o Increased blood pressure Vasopressin signalling through V2 receptors: o Water in urine is reabsorbed during passage through tubules o ADH signals through V2 receptors in collecting tubules to maximally concentrate urine o V2 signaling activates a G protein, which activates adenylyl cyclase and increases cAMP o Cascade of reactions leading to increased permeability of epithelial cells of collecting tubules to water Control of release Osmotic control of ADH secretion: o Lack of wate
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