SOMATOSTATIN PLAYS A DUAL, STIMULATORY INHIBITORY ROLE IN THE CONTROLOF GROWTH-HORMONE SECRETION BY 2 SOMATOTROPE SUBPOPULATIONS FROM PORCINE PITUITARY/

Previous results from our laboratory demonstrated the existence of two subpopulations of porcine somatotropes of low-(LD) and high density ( HD) that exhibit differences in ultrastructure and respond in an oppos ite manner to somatostatin (SRIF) in vitro. In LD cells, SRIF did not affect basal growth hormone (GH) release but partially blocked the sti mulatory effect induced by GH-releasing factor (GRF). Conversely, SRIF paradoxically stimulated the secretory activity of HD somatotropes. H ere, we have analysed in detail the basic parameters that characterize this differential response, To this end, tie time-and dose-dependent effects of SRIF-14 were evaluated on separate monolayer cultures of bo th subpopulations. Likewise, the direct effect of the peptide on indiv idual somatotropes from each subset was assessed by cell immunoblot as say. Finally, we compared the effects of SRIF-14 and SRIF-28 on cultur es of LD and HD cells. SRIF-14 (10(-7) M) induced a rapid (30 min) and sustained (4 h) 2-fold increase in GH release from HD cells, whereas it did not affect GH secretion from LD somatotropes. Surprisingly, a l ow dose of SRIF (10(-15) M) stimulated GH release from both LD (154.1 +/- 8.2% of basal, P <0.05) and HD (337.2+/-55.5% of basal, P<0.05) su bpopulations, even more effectively than higher doses of the peptide. Results from cell blotting showed that SRIF stimulatory effects were e xerted directly upon individual somatotropes. Finally, SRIF-28 elicite d similar responses to those observed for SRIF-14 in both somatotrope subpopulations, yet 10(-15) M SRIF-28 was less potent than the same do se of SRIF-14 in stimulating GH release from HD cells. Our present fin dings demonstrate that SRIF can function as a true GH-releasing factor in cultures of porcine pituitary cells by acting specifically and dir ectly upon somatotropes. Furthermore, together with previous observati ons, these results strongly suggest that SRIF is not merely an inhibit or of GH release in pigs, but might play a dual modulatory role, Heter ogeneity of the somatotrope population contributes greatly to this div ergent effect of SRIF.