Hormone ontogeny in the ovine fetus. XXV. Somatotrope desensitization to growth hormone releasing factor (GRF) independent of short-latency, ultrashortloop GH feedback.

Plasma ovine growth hormone (oGH) concentrations are strikingly elevated in the ovine fetus and decline at birth towards the low levels observed in the newborn lamb. We postulated that developmental changes in somatotrope function secondary to GH-releasing factor (GRF) desensitization and GH feedback play a role in the developmental pattern of oGH secretion and tested this hypothesis in vito in chronically catheterized ovine fetuses (123-145 days gestation; term 147 days) and newborn lambs (1-18 days). In the first set of studies, two consecutive intravenous GRF(1-44 amide) boluses (1 microgram/kg) were administered. When the GRF boluses were given 90 min apart, they elicited similar oGH responses, both in fetuses and in newborn lambs. In contrast, when the GRF boluses were given 20 min apart, a significant oGH response was evoked by the first GRF but an oGH response was not detected after the second GRF, either in fetuses or in newborn lambs. When the oGH response GRF(1-44 amide; 1 microgram/kg i.v.) was evaluated 40 min after the start of a human GH infusion (25 micrograms/kg hGH bolus followed by 0.5 microgram/kg/min hGH for 80 min, resulting in mean hGH plasma concentrations of 80 ng/ml), the exogenous hGH did not after the oGH response to GRF, either in fetuses or in newborn lambs. The present in vivo results demonstrate that the fetal and the neonatal somatotrope can be desensitized to GRF and suggest that a short-term latency, ultrashortloop GH feedback mechanism is not operative, either in the ovine fetus or in the newborn lamb.(ABSTRACT TRUNCATED AT 250 WORDS)