Molecular mechanisms of phorbol ester, thyrotropin-releasing hormone, and growth factor stimulation of prolactin gene transcription

• Published in: The Journal of biological chemistry Vol. 260; no. 21; pp. 11852 - 11858
• Main Authors: Murdoch, G H, Waterman, M, Evans, R M, Rosenfeld, M G
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 25-09-1985; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Biological and medical sciences; Calcium - physiology; Cells, Cultured; Epidermal Growth Factor - pharmacology; Fundamental and applied biological sciences. Psychology; Gallopamil - pharmacology; Gene expression; Molecular and cellular biology; Molecular genetics; Nifedipine - pharmacology; Phorbols - pharmacology; Phosphorylation; Prolactin - genetics; Prolactin - metabolism; Protein Kinase C - physiology; Rats; Tetradecanoylphorbol Acetate - pharmacology; Thyrotropin-Releasing Hormone - pharmacology; Transcription, Genetic - drug effects; Human; TSH-RH; Regulation(control); Transcription; Prolactin; Tumor promotor; Peptide hormone; Hormonal regulation; Activation; Gene expression; Glycoprotein hormone; Growth factor
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)39109-3

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.