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Adrenal Function I

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BIOL 1840U
Peter Cheung

Adrenal Function I. Anatomy & Embryology a. Blood supply i. Cortex—arises from capsular plexus & distributes in an anastomosing network; converge in zona reticularis ii. Medulla—dual blood supply; arterial blood from capsular plexus & venous supply from portal system (comes from cortex branch) 1. portal blood has high concentration of hormones from cortex => effect on medullary fxn b. Embryology i. Cortex—derived from mesoderm along with gonads & kidneys ii. Medulla—derived from neural crest cells (migrate in after cortex cells begin to differentiate) iii. Zones of Cortex during development: 1. fetal zone—very large, inner zone that begins to involute at birth => zona reticularis a. produces androgens (DHEA) during development, but stops at birth b. at 6-7 yrs of age, zona reticularis becomes active again & begins to produce androgens (process = adrenarche) c. ACTH is permissive for adrenarche, but is not the stimulus 2. definitive zone—small in fetus; begins to expand at birth => zona fasciculata iv. Molecular Embryology 1. development of adrenals are dependent on proper activation of many transcription factors a. WT1—expressed in urogenital ridges; mutation => abnormal kidneys, adrenals, & gonads b. Lim1—expressed in urogenital ridges; mutation => embryonic lethal c. SF-1—necessary for differentiation of cells; mutation => loss of adrenals & gonads d. DAX-1—necessary for differentiation of cells; mutation => loss of adrenal gland development II. Adrenal Cortex a. Steroidogenesis i. Are all steroid hormones; synthesized from precursor cholesterol 1. cholesterol is stored in large quantities in cortex cells 2. finished hormones are not stored => diffuse immediately ii. Steps in Steroidogenesis 1. transport into mitochondria via StAR (steroidogenic acute regulatory protein) 2. cholesterol  pregnenolone via SCC (side-chain cleavage enzyme) **Rate limiting Step** 1 3. multiple enzymatic reactions in mitochondria & SER => final product steroid hormones * SCC—determines how much hormone is made * P450c17—determines which hormones are made iii. Zona Glomerulosa—no 17α-hydroxylase is present & aldosterone synthase IS present => produce mineralocorticoid (aldosterone) iv. Zona Fasciculata—activity of 17α-hydroxylase predominates => produce glucocorticoids (cortisol) v. Zona Reticularis—17-20 lyase activity predominates => produce androgens (DHEA & androstenedione) * androgens are 19-C steroids b/c of 17-20 lyase activity b. Mechanism of Steroid Hormone Action i. cross cell membrane & bind to receptor (a member of the nuclear receptor superfamily) ii. action is mediated by stimulation or repression of expression of genes w/ binding sites for hormone receptors c. Glucocorticoids (Zona Fasciculata) i. cortisol = hydrocortisone (human glucocorticoid) ii. circulates mainly in bound form, but only unbound is free => bound serves as reservoir iii. Actions—↑ hepatic glucose, ↑ glycogen synthesis; ↑ vascular responsiveness to norepinephrine iv. Fxn—to prevent fasting hypoglycemia & prevent hypotension * may also be used as an anti-inflammatory or leukemia txt v. Cortisol is a stress hormone => levels rise significantly when stressed / injured vi. Control 1. ACTH—produced in pituitary => ↑ cortisol synthesis 2. CRH—(hypothalamus) => ↑ ACTH secretion 3. Negative Feedback Loop—cortisol inhibits ACTH & CRH
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