EFFECTS OF GROWTH-HORMONE (GH)-RELEASING FACTOR AND SOMATOSTATIN ON GH SECRETION FROM EARLY TO MIDGESTATION HUMAN FETAL PITUITARIES

Using explant cultures of human anterior pituitary glands (9-19 weeks fetal age) and an acute (3-h) test protocol, we investigated fetal somatotrope responsiveness to human GH-releasing factor [hGRF-(1-44)] and somatostatin [SRIF-(1-14) and SRIF-(1-28)] as a function of age. Ontogenic data were analyzed using three age groups: 9-10, 12-13, and 15-19 weeks fetal age. Both daily (24-h) and acute test (3-h) basal GH secretion increases as a function of fetal age, with the greatest increase occurring after 12-13 weeks; however, the 3 h/24 h secretion ratio remains unchanged, at approximately 12%. GRF (0.1-10 nm) stimulates GH release in a dose-related fashion, regardless of fetal age; there is a significant increase in the response to both 1 nm (P < 0.05) and 10 nm (P < 0.01) GRF between 9-10 and 15-19 weeks fetal age and to 10 nm GRF (P < 0.05) between 12-13 and 15-19 weeks. Pretreatment of cultures (9-19 weeks) with 1 or 10 nm GRF for 24 h does not alter basal 3-h GH secretion, but significantly decreases subsequent responses to 1 or 10 nm GRF, respectively (P < 0.01). Pretreatment with 1 nm GRF does not alter a subsequent 3-h response to 10 nm GRF. SRIF-(1-14) (1-100 nM) causes a dose-related inhibition of basal GH secretion from as early as the ninth week of fetal life; there is a small age-related increase in the somatotrope response to 100 nm SRIF-(1-14) between 12-13 and 15-19 weeks fetal age (P < 0.05). In a group of 11- to 14-week-old fetal pituitaries, SRIF-(1-28) had a significantly (P < 0.05) greater inhibitory effect than SRIF-(1-14) at both 1 and 10 nm; the two peptides decreased basal GH secretion to a similar extent at 100 nm (52.8 +/- 4.0% of control value; P < 0.01). SRIF-(1-14) (10 and 100 nm) does not significantly alter 10 nm GRF-stimulated GH release from 9- to 10-week-old fetal pituitaries. However, by 12-13 weeks, 10 nm SRIF-(1-14) reduces GRF-stimulated GH secretion by 60% (P < 0.01), while 100 nm SRIF-(1-14) decreases it by 80% (P < 0.01); similar inhibitory effects are observed with 15- to 19-week-old fetal somatotropes. In a group of 11- to 14-week-old fetal pituitaries, SRIF-(1-28) had a significantly (P < 0.01) greater inhibitory effect than SRIF-(1-14) on GRF-stimulated GH release. Pretreatment of cultures (9-17.5 weeks) with 100 nm SRIF-(1-14) had no effect on subsequent 3-h basal, GRF-stimulated, or SRIF-inhibited GH release. These data demonstrate that 1) from 9-19 weeks of fetal life, there is a significant increase in fetal somatotrope activity (basal, GRF-stimulated, and SRIF-inhibited), with the greatest changes occurring after 12-13 weeks; 2) 24-h pretreatment with GRF causes a partial desensitization of the fetal somatotrope to subsequent 3-h GRF stimulation, while a similar pretreatment with SRIF has no effect; and 3) SRIF- (1-28) is often more potent than SRIF-(1-14) in inhibiting basal as well as GRF-stimulated GH secretion.