Hormone ontogeny in the ovine fetus: XIX: The effect of a potent luteinizing hormone-releasing factor agonist on gonadotropin and testosterone release in the fetus and neonate

S. J. Clark, B. P. Hauffa, K. P. Rodens, Dennis M Styne, S. L. Kaplan, M. M. Grumbach

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

To investigate further the role of the hypothalamic luteinizing hormone releasing factor (LRF) pulse generator and the pituitary LRF receptor in the regulation of gonadotropin secretion and gonadal steroidogenesis in the ovine (O) fetus and neonatal lamb, we measured the increment (the difference between the concentration of plasma LH at time O and peak LH) in oLH (ΔoLH) and oFSH (ΔoFSH) responses to a potent LRF agonist, D-Trp6Pro9NEt-LRF (LRF-A), after consecutive daily doses in 17 ovine fetuses (six females, 11 males) and in 15 neonatal lambs (six females, nine males). Seven of the lambs had been studied as fetuses. In addition, plasma concentrations of testosterone (T) and androstenedione (Δ4A) were measured in nine male fetuses. After a stimulatory reponse to the first dose of LRF-A, the mean ΔoLH and ΔoFSH responses in the 106- to 118-d gestation fetuses of both sexes were significantly suppressed by the fourth dose and in the neonatal lamb by the second dose. Suppression was sustained throughout the duration of LRF-A therapy which included the gestational interval when the fetal pituitary exhibits its greatest responsiveness to an acute dose of synthetic LRF. The duration of oLH and oFSH suppression after cessation of LRF-A therapy was studied by measuring the ΔoLH and ΔoFSH responses to LRF before and at intervals after LRF-A therapy. In the fetus, the ΔoLH and ΔoFSH responses remained significantly decreased 7-8 d after the agonist was discontinued. No statistical differences were detected in the ΔoLH and ΔoFSH responses to LRF in the neonatal lamb at least by the 4th d after discontinuation of LRF-A. Increasing the duration of LRF-A therapy did not prolong the length of recovery of LH and FSH responsiveness to LRF in either fetus or neonate. Mean fetal plasma T levels rose significantly in response to a single dose of LRF or LRF-A. Peak T responses to single dose LRF or LRF-A were lower on d 2-4 and d 7 than on the 1st d of LRF-A administration. These changes coincided with the decrease in the release of oLH and oFSH. Peak T responses to a single dose of LRF or LRF-A had not returned to pretreatment levels by d 1-5 after discontinuation of chronic LRF-A administration in the male fetus. Plasma Δ4A concentrations were not affected by chronic exposure to LRF-A. The results show that secretion of FSH and LH in the midgestation fetus is LRF-dependent. The induction of LRF desensitization in the fetal gonadotrope suggests that pulsatile gonadotropin secretion in the fetus is a consequence of pulsatile release of LRF. A relatively delayed recovery of LH and FSH responsiveness in the fetus may be due to a functional immaturity of the gonadotropes and their capacity to recover from desensitization, including down-regulation of LRF receptors. The increase in the concentration of testosterone after the administration of LRF is evidence of the bioactivity of fetal oLH.

Original languageEnglish (US)
Pages (from-to)347-352
Number of pages6
JournalPediatric Research
Volume25
Issue number4 I
StatePublished - 1989

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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