Prolactin-induced polyamine biosynthesis in spleen and thymus: specific inhibition by cyclosporine.
The induction of ornithine decarboxylase (ODC) in the rat spleen and thymus in response to prolactin shows a dose-dependent sensitivity to cyclosporine (CsA), a known immunosuppressive drug. Marked inhibition of prolactin-stimulated ODC activity occurred at 0.12 mg CsA/kg body weight, and nearly total inhibition was detected at 1.2 mg CsA/kg, a dose comparable to that used to suppress organ rejection processes. CsA blocked ODC induction in response to prolactin injection in both intact and hypophysectomized rats, suggestive of a direct effect of prolactin on spleen and thymus. Furthermore, we were able to demonstrate specific 125I-prolactin binding sites on the rat spleen and thymus. Although growth hormone was capable of elevating ODC activity in spleen, this elevation was not inhibited by CsA. ODC activity in response to cyclic AMP-mediated hormones and to steroid analogs such as dexamethasone was not affected by CsA. Agents known to alter calcium channeling mostly had random enhancing capacity when administered with CsA. The most potent elevation occurred in spleens in response to aminophylline plus CsA. It should be noted, however, that aminophylline alone slightly inhibited the basal level of ODC in the spleen. Insulin, which elevated ODC in the thymus and spleen in a dose-dependent manner, also was not affected by concurrent CsA administration. Prolactin administration altered the RNA and DNA content of spleen and thymus indicating its ability to alter metabolic function. We conclude that prolactin may regulate immune function in spleen and thymus. Studies are in progress to identify the regulation of specific gene products by prolactin.
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Larson
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D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D003524:Cyclosporins / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology; D007016:Hypophysectomy; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009696:Nucleic Acids / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011073:Polyamines / Q000096:biosynthesis*; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D011981:Receptors, Prolactin; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D003524:Cyclosporins; D006728:Hormones; D009696:Nucleic Acids; D011073:Polyamines; D011956:Receptors, Cell Surface; D011981:Receptors, Prolactin; D009020:Morphine; D011388:Prolactin; D000242:Cyclic AMP; D009955:Ornithine Decarboxylase