Hormone Ontogeny in the Ovine Fetus

Abstract

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 µg/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 µg/kg i.v.) was evaluated 40 min after the start of a human GH infusion (25 µg/kg hGH bolus followed by 0.5 µg/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. The remarkable similarity of the fetal and the neonatal results relative to GRF desensitization and GH feedback suggests that the striking perinatal decrease in oGH secretion and somatotrope responsiveness is independent of these two mechanisms. Moreover, in light of earlier studies, it cannot be attributed at least in the fetus, to somatostatin.

Effects of insulin on ovine fetal leucine kinetics and protein metabolism.

“…To avoid the possibility that changes of fetal glucagon concentration that may occur with fetal insulin infusion (33) would independently affect protein metabolism (34,35), we infused somatostatin to minimize endogenous glucagon release and infused exogenous glucagon to maintain normal glucagon concentrations throughout the experiments. Somatostatin also decreases fetal growth hormone secretion (36), but this fact should not influence the present study for two reasons. First, fetal growth is not dependent on growth hormone (37).…”

The Ontogeny of Growth Hormone, Insulin-Like Growth Factors and Sex Steroids: Molecular Aspects

“…The GH mRNA abundance in the pituitary increases 15-fold between 16 and 27 weeks gestation [10], and the circulating GH levels concomitantly increase from 2 nM at 12 weeks gestation to 8 nM at 22 weeks and then decline to 1-2 nM at term [11], This pattern of GH secretion results most likely from the increasing sensitivi ty of the pituitary to GH-releasing factors during midges tation, followed by increasing prominence of somatosta tin in the latter part of gestation [12], In the fetal mouse, GH and prolactin mRNA are first identified on day 15.5 ot gestation, but based on the initial cellular localization in which prolactin cells (mammotrophs) are located in the ventromedial region, and GH cells (somatotrophs) are sit uated in the lateral and central region of the pars distalis, they develop from different groups of committed cells [13], The placenta is another source of peptides of the GH gene locus, namely the GH variant (GH-V) and PLs. GH-V is synthesized by the syncytiotrophoblasts and released only into the maternal circulation [14].…”