Stimulation of chicken growth hormone release by phorbol esters.
Synergism between thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) has been shown in a primary (48 hr) culture of chicken adenohypophyseal cells established in this laboratory. The purpose of the present study was to determine if phorbol esters acting alone or in concert with TRH or hpGRF affect chicken GH release. Collagenase-dissociated chicken adenohypophyseal cells were treated (2 hr) with combinations of TRH, hpGRF, phorbol esters (activators of protein kinase C; PKC), and pharmacologic agents that increase cAMP. Phorbol myristate acetate (PMA) or phorbol dibutyrate (PDBu) alone stimulated GH release in a dose-dependent manner; either phorbol ester (10(-6) M) increased GH release from 100 to 390% over the value obtained in the absence of test agents (control). Similarly, hpGRF (10(-9) M), 8 Br-cAMP (10(-3) M), forskolin (10(-6) M), or isobutylmethylxanthine (IBMX, 10(-3) M) alone elevated GH release by at least 60% over the control value. The combined effects of phorbol esters (either PMA or PDBu) and hpGRF, 8 Br-cAMP, or forskolin on GH release were additive. Only one combination, phorbol esters with IBMX, exerted synergistic effects on GH release. No synergy was shown between TRH (1.3 x 10(-9) M) and either phorbol ester. These findings are the first to implicate PKC in chicken GH release in vitro. In addition, these studies, together with previous results, suggest that TRH and hpGRF synergy occurs via a pathway that arises prior to activation of PKC.
Perez
F M
FM
Department of Anatomy, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
Malamed
S
S
Scanes
C G
CG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002645:Chickens / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D010703:Phorbol Esters; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015240:Phorbol 12,13-Dibutyrate; D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine