Regulation of Growth Hormone mRNA and Pro-Opiomelanocortin mRNA Levels by Cyclic AMP in Rat Anterior Pituitary Cells in Culture

Abstract

To understand the hormonal regulation of steady-state growth hormone (GH) mRNA levels, we investigated the interaction between somatostatin and agents known to increase intracellular cAMP activity on GH mRNA, GH synthesis, cell content of GH, and GH release in primary cultures of rat anterior pituitary cells. We simultaneously studied the modulation of the steady-state of pro-opiomelanocortin (POMC) and mRNA levels by cAMP. In four independent experiments, a 48-hr exposure to 0.3 mM 3-isobutyl-1-methylxanthine (IBMX) or 3 mM 8-bromoadenosine 3'',5''-cyclic monophosphate (8Br-cAMP) increased GH mRNA levels from 70 to 170% and from 70 to 150% above control (p < 0.001), respectively. Parallel increases in GH release accompanied by a corresponding decrease in the intracellular content of GH were also obtained. Following a 48-hr incubation with 100 nM somatostatin alone, no change in GH mRNA levels was observed whereas GH release was inhibited by 90%, GH cell content doubled, and GH synthesis decreased by 40%. Surprisingly, somatostatin potentiated the enhancing effect of 8Br-cAMP on GH mRNA levels. In the same cell preparation, a 48-hr exposure to IBMX or 8Br-cAMP stimulated adrenocorticotropin release by 9.4- and 18.0-fold, respectively, and increased POMC mRNA levels by 2.4- and 2.3-fold (p < 0.001), respectively. No change in .beta.-actin mRNA was observed after these treatments. These data indicate that increased intracellular cAMP concentrations increase the steady-state level of GH mRNA. In addition, somatostatin alone, despite its potent inhibitory effect on GH release, fails to inhibit GH mRNA levels, but, rather, it enhances the stimulatory effect of 8Br-cAMP on GH mRNA levels. These data also demonstrate, for the first time, that cAMP enhances POMC mRNA accumulation.