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|Title:||Studies of Aldosterone Synthase-Antibody-Reactive-Proteins in the ACTH-Stimulated Adrenal Gland||Authors:||Inchirah N. Iskandarani||Supervisor:||Dr. Behling Cheng||Keywords:||Aldosterone Synthase-Antibody-Reactive-Proteins , ACTH-Stimulated Adrenal Gland||Issue Date:||2016||Publisher:||Kuwait university - college of graduate studies||Abstract:||Rat adrenocortical tissue is organized into three concentric zones with a centripetal distribution from glomerulosa (ZG), fasciculata (ZF) to reticularis (ZR). ZG expresses aldosterone synthase (CYP11B2) and synthesizes aldosterone, whereas ZF and ZR produce corticosterone. Aldosterone-target cells express 11β-hydroxysteroid dehydrogenase-II (11βHSD-II) to protect the binding of aldosterone to mineralocorticoid receptor (MCR) against glucocorticoid interference. Stimulation of rats with ACTH for four consecutive days results in elevated corticosterone production without a decrease in aldosterone synthesis. The hormone action sustains the CYP11B2 protein level and induces a 68 kDa protein, detected by Western blot using an anti-CYP11B2-antibody. The present research was designed to (I) further characterize CYP11B2 and the 68 kDa protein in ACTH-stimulated rats, and (II) determine if ACTH up-regulates the adrenal MCR protein level. The results are summarized as follows. (a) The cells immunostained for CYP11B2 primarily reside in ZG. Strikingly, ACTH stimulation causes a pronounced appearance of the cells throughout ZF and ZR, but less in ZG. Since ACTH action reportedly suppresses CYP11B2 gene expression, the altered distribution might be a consequence of accelerated migration of the cells into the inner cortex. (b) ACTH stimulation up-regulates adrenal MCR protein level by 127%. Treatment of rats with dexamethasone (which blocks the endogenous ACTH) down-regulates the protein level. The cells immunostained for MCR predominantly reside in ZG, but become scattered throughout the inner cortex upon the hormone stimulation. (c) Subcellular fractionation studies revealed that MCR and 11βHSD-II are both localized in the microsomal fraction. ACTH-stimulation does not result in the translocation of MCR into the nuclear fraction, suggesting a non-genomic mechanism. Unexpectedly, a sub-fraction of CYP11B2 (but not CYP11B1 and cytochrome oxidase) was observed in the cytosol, although they are all mitochondrial enzymes. (d) Study of the 68 kDa protein by two different anti-CYP11B2-antibodies indicates that the previous observation of the protein was nonspecific. Above data support a hypothesis that aldosterone may act as an autocrine/paracrine signal to regulate glucorticoidogenesis, through a synchronized mechanism by which CYP11B2-expressing cells and increased MCR protein levels are both made available in the inner adrenal cortex to cope with repetitive ACTH-stimulation.||URI:||http://hdl.handle.net/123456789/354|
|Appears in Programs:||0540 Medical Biochemistry (M.Sc.)|
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