Rapamycin, FK506 and cyclosporin A inhibit human prolactin gene expression.
In this work we demonstrate that transcription of the human prolactin gene is inhibited by the immunosuppressants FK506 (IC50 = 25 nM), cyclosporin A (IC50 = 190 nM) and rapamycin (IC50 = 25 nM). Whereas the effect of FK506 and cyclosporin A is specific for prolactin gene transcription, rapamycin has a more general effect on transcription and/or translation in pituitary cells. In view of recent work demonstrating the immunoactivating role of prolactin, these results suggest that inhibition of prolactin gene expression in the pituitary may contribute to the mechanism of action of immunosuppressants.
Wera
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Laboratoire de Biologie Moléculaire et de Génie Génétique, Université de Liège, Sart-Tilman, Belgium.
Belayew
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Martial
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JA
D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D011090:Polyenes / Q000494:pharmacology*; D011388:Prolactin / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D051381:Rats; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D011090:Polyenes; D016572:Cyclosporine; D011388:Prolactin; D000242:Cyclic AMP; D020123:Sirolimus; D016559:Tacrolimus