ADRENOCORTICAL INSUFFICIENCY - STUD：肾上腺皮质功能不全-螺柱.ppt

ADRENOCORTICAL INSUFFICIENCY THE ADRENALCORTEXBASIS CONCEPTS ADRENOCORTICAL HISTOLOGY The adrenal cortex is composed of three concentric zones with distinct steroid biosynthetic capacities. Zona glomerulosa – biosynthesis of mineralocorticoids Zona fasciculata – biosynthesis of glucocorticoids Zona reticularis – biosynthesis of adrenal androgens. STEROID BIOSYNTHESIS Steroidogenesis results from specific sequential enzymatic conversions of cholesterol substrate into steroid hormones, which exert a wide variety of biological activities. STEROID BIOSYNTHESIS A series of steroidogenic enzymes are compartmentalized either in the mitochondria or in the endoplastic reticulum. Several of these enzymes belong to the superfamily of mixed function oxidase enzymes known as cytochrome P450. STEROID BIOSYNTHESIS Approximately ~80% of adrenal cholesterol sources are provided by circulating low density lipoprotein (LDL). The adrenal cells can also synthesize cholesterol de novo from acetyl coenzyme A. STEROID BIOSYNTHESIS The first rate-limiting step in steroidogenesis involves the removal of six carbons from the lateral chain of cholesterol by integral inner mitochondrial membrane P450 side chain cleavage (CYP11A1) enzyme to generate pregnenolone. Nomenclature for steroidogenic enzymes now utilized Main steroid biosynthetic pathways (mineralocorticoids and glucocorticoids). Main steroid biosynthetic pathways (adernal androgens). REGULATION OF GLUCOCORTICOID SECRETION The secretion of cortisol is regulated by several levels of signals and interactions between the brain, the hypothalamus, the pituitary, and the adrenal glands. Regulation of the hypothalamic-pituitary-adrenal axis. CORTICOTROPIN-RELEASING HORMONE(CRH) ? 41-aminoacid peptide synthesized by neurons in the paraventricular hypothalamic nucleus Action: ? mRNA levels of pro-opiomelanocortin (POMC), the polypeptide precursor of ACTH ADRENOCORTICOTROPIC HORMONE [ACTH] ? 39-aminoacid peptide capable of stimulat