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Hormone Ontogeny in the Ovine Fetus and Neonatal Lamb. XX. Effect of Age, Breeding Season, and Twinning on the Growth Hormone (GH) Response to GH-Releasing Factor: Evidence for a Homeostatic Role of Fetal GH^*

FRANCIS DE ZEGHER, DENNIS M. STYNE, JORGE DAABOUI, MARKUS BETTENDORF, SELNA L. KAPLAN and M. M. GRUMBACH^||

Department of Pediatrics, University of California, San Francisco San Francisco, California 94143-010

Abstract

The ovine GH (oGH) response to GRF (1–44 amide) was evaluated in 74 chronically catheterized fetal and neonatal lambs. After a 1-h control period, GRF was administered iv, and the oGH response was studied during the next 60 min. The following variables were analyzed: GRF dose, fetal or neonatal age, breeding season, and singleton or multiple pregnancy. One and 10 µg/kg GRF elicited a similar oGH response, which was greater (P < 0.001) than the response to 0.1 Mg/kg GRF.

GRF-stimulated oGH release was strikingly age dependent. The mean peak incremental oGH response in fetuses of 89–122 days gestation (294 ± 55 ng/ml) was higher (P < 0.05) than that in fetuses of 127-145 days gestation (136 ± 19 ng/ml); the fetal response was much greater (p < 0.005) than the mean peak increment in neonatal lambs (46 ± 7 ng/ml).

A remarkable difference in basal and GRF-induced oGH secretion was observed in both fetuses and lambs of ewes bred in the normal breeding season (on-season) and those bred out of season (off-season). In the neonatal lamb, the mean basal oGH concentration was higher (p < 0.005) in the on-season (12 ± 2 ng/ml) than in the off-season (7 ± 0.5 ng/ml) neonatal lambs, as was the mean peak incremental oGH response to GRF (70 ± 12 vs. 33 ± 7 ng/ml; p < 0.01). In contrast, in singleton, late gestational fetuses (127–145 days), the mean basal oGH concentration was lower (p < 0.03) in the on-season (74 ± 9 ng/ ml) than in the off-season (124 ± 18 ng/ml) fetuses, as was the mean peak incremental oGH response to GRF (136 ± 9 vs. 292 ± 41 ng/ml; p < 0.005). Further, compared to the on-season, late gestational singletons, on-season twin fetuses had higher (p < 0.0001) basal oGH levels (199 ± 19 ng/ml) and peak incremental oGH responses (248 ± 11 ng/ml). Moreover, off-season twin fetuses had the highest basal GH concentrations and the most striking increment in GH concentration after GRF treatment of any of the groups.

The strikingly age-dependent pattern of the GRF-induced oGH response in fetal and neonatal lambs is compatible with the concept that the inhibitory influences or their effects on the somatotrope increase gradually during late gestation and sharply at birth. The observations in on- and off-season singleton twin fetuses suggest that maternal nutrition has a major influence on GH secretion in the fetus and neonate and support a homeostatic role for GH in late gestational fetal metabolism. The results indicate that in the ovine fetus, gestational age, breeding season, and twinning have a profound effect on basal GH release and the rise in GH elicited by GRF; breeding season has a postnatal effect on GH secretion in the neonatal lamb. (Endocrinology 124: 124–128,1989)

Footnotes

^* This work was supported in part by a grant from the NICHHD, NIH.

Fellow in Pediatric Endocrinology, supported by the Belgian American Educational Foundation and the Belgian Fund for Scientific Research (N.F.W.O.).

Trainee in Pediatric Endocrinology under a program sponsored by the NIDDK, NIH, and the USPHS.

Fellow in Pediatric Endocrinology, supported by the Deutsche Forschungsgemeinschaft (DFG).

^|| To whom requests for reprints should be addressed.

Received April 11, 1988.

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