Molecular mechanisms of phorbol ester, thyrotropin-releasing hormone, and growth factor stimulation of prolactin gene transcription.
The polypeptide thyrotropin-releasing hormone (TRH) and epidermal growth factor (EGF) stimulate, within seconds to minutes, the transcription of the prolactin gene in a rat pituitary cell line (GH4). Because a series of agents that act to stimulate prolactin secretion fail to alter prolactin gene transcription, it is suggested that secretory events are neither obligatory for nor causal of hormone-induced transcriptional stimulation. Elevation of cytosolic-free calcium does not stimulate prolactin gene transcription; however, several agents that act to antagonize calcium-dependent processes inhibit or abolish both TRH and EGF stimulation of prolactin gene transcription and a specific hormone-dependent nuclear phosphorylation. In contrast, inhibitors of the slow calcium channel exert minimal effects on TRH-stimulated prolactin gene expression, suggesting that calcium influx through membrane channels is not crucial for the observed nuclear actions of TRH. Activation of protein kinase C by phorbol esters mimics the nuclear actions of TRH. In the presence of increased intracellular calcium levels, the effects of 12-O-tetradecanoyl phorbol 13-acetate on prolactin gene transcription are quantitatively identical to those observed in response to TRH or EGF.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005711:Gallopamil / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D010704:Phorbols; D005711:Gallopamil; D013973:Thyrotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D011388:Prolactin; D011493:Protein Kinase C; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium