title: Effect of phorbol esters on the release of growth hormone and prolactin from rat pituitary cells cultured in monolayer.
abstract: The effect of phorbol diester tumour promoters on the release of growth hormone (GH) and prolactin (Prl) was studied in rat pituitary cells cultured in monolayer. 12-O-tetradecanoyl phorbol-13-acetate (TPA), the most potent phorbol ester, stimulated GH accumulation in the cultured medium in a dose-dependent manner. TPA also stimulated Prl accumulation. A time course study indicated that TPA mainly stimulates release of GH. The maximal stimulation of GH release by TPA (100 ng/ml) was 3-4-fold over control. Phorbol-12,13-dibutyrate (PDB), another tumour-promoting phorbol ester, stimulated GH release to an extent similar to that of TPA, while a biologically inactive compound, phorbol-12,13-diacetate (PDA), had no effect. TPA-stimulated GH release was not affected by the presence of indomethacin, an inhibitor of prostaglandin (PG) synthesis, indicating that PG is not involved in the process of TPA-stimulated GH release. Co++, a competitive antagonist of Ca++, at 2.0 mM completely suppressed the GH release induced by TPA, and this inhibition was partially reversed by the addition of 2.0 mM Ca++. Verapamil, a Ca++ channel blocker, reduced TPA-stimulated GH release, and trifluoperazine, an inhibitor of Ca-calmodulin formation, had a similar effect. Somatostatin (SRIF) also inhibited the GH release by TPA. These observations are compatible with the idea that Ca++ may be involved in the process of TPA-stimulated GH release. Since TPA has been reported to activate a Ca++- and phospholipid-dependent protein kinase (protein kinase C), it is possible that TPA stimulate GH release by activating the enzyme. Further studies are required to clarify this point.
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D013006:Growth Hormone / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D010703:Phorbol Esters; D010704:Phorbols; D014268:Trifluoperazine; D013004:Somatostatin; D011388:Prolactin; D013006:Growth Hormone; D014700:Verapamil; D006821:Hyaluronoglucosaminidase; D002118:Calcium; D007213:Indomethacin