Effects of adrenalectomy on CRH regulation of ACTH release: adenylate cyclase activity, cyclic AMP-dependent protein kinase activity and ACTH release.
Corticotropin releasing hormone (CRH) stimulation of ACTH release and cyclic AMP-mediated events involved in the control of ACTH release were compared in sham-operated and adrenalectomized rats. CRH-stimulated adenylate cyclase activity was decreased in pituitary homogenates from adrenalectomized animals. CRH-stimulated cyclic AMP accumulation was essentially abolished and CRH-stimulated cyclic AMP-dependent protein kinase (A-kinase) activity was decreased in freshly prepared anterior pituitary cells from adrenalectomized animals. Basal and CRH-stimulated ACTH release was elevated in these cells. Since ACTH release is increased in adrenalectomized rats despite the down regulation of CRH-linked pituitary mechanisms, we speculate that the site of action of disinhibition by corticosterone of ACTH release (or synthesis) following adrenalectomy is distal to the generation of cyclic AMP and/or that non-CRH mediated mechanisms assume a greater role in ACTH regulation following adrenalectomy.
Dhillon
G S
GS
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Oleshansky
M A
MA
Kant
G J
GJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011494:Protein Kinases; D000262:Adenylyl Cyclases