Cyclosporine inhibits prolactin induction of ornithine decarboxylase in rat tissues.
Cyclosporine (CyA), formerly cyclosporin A, significantly inhibited the ability of prolactin (PRL) to elevate ornithine decarboxylase (ODC) activity in a variety of rat tissues. Administration of PRL to hypophysectomized rats also resulted in an induction of ODC activity which was inhibited markedly in all tissues studied in the presence of CyA. Transglutaminase ( TGase ) activity was not affected in any significant manner by PRL or CyA in most tissues studied. However, it was elevated in the adrenal by 10(-8) M PRL. Bromocryptine, which selectively antagonizes pituitary PRL release, decreased the kidney ODC basal levels to 30% of vehicle control and serum PRL level to 4.3 +/- 1.4 compared to 28 +/- 10 in controls, suggestive of PRL maintenance of steady-state ODC activity in the kidney. CyA administration did not affect the action of glucagon, a known cyclic AMP-mediated hormone, or 8-bromo-cyclic AMP on kidney ODC activity. The elevation of rat kidney ODC activity by dexamethasone and triiodothyronine (T3), compounds which elevated serum prolactin levels in all cases, was also blocked by administration of CyA. Epidermal growth factor (EGF), which did not induce rat kidney ODC activity by itself, was capable of producing a small increment in ODC activity in the presence of CyA. The marked effect of CyA to selectively block ODC induction by PRL may be due to the ability of CyA to interact with receptor-required phospholipids in membranes and thus to antagonize hormone-receptor interaction.
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology*; D004790:Enzyme Induction; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D007016:Hypophysectomy; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011503:Transglutaminases
D003524:Cyclosporins; D006728:Hormones; D007328:Insulin; D001971:Bromocriptine; D011388:Prolactin; D013006:Growth Hormone; D000242:Cyclic AMP; D000217:Acyltransferases; D011503:Transglutaminases; D009955:Ornithine Decarboxylase