Ontogenesis of Gonadotropin-Releasing Hormone in the Human Fetal Hypothalamus

Summary

Gonadotropin-releasing hormone (GnRH) was measured by radioimmunoassay in 44 human fetal hypothalamic and 33 cerebrocortical specimens of 8-17.5 weeks fetal age. These specimens, obtained within 30 min of hysterotomy, were frozen in 0.1 N HC1 and subsequently homogenized and extracted in acid. Attempts to extract GnRH in additional hypothalamic specimens under either neutral (n = 6) or acid (n = 8) conditions from tissue frozen without acid resulted in considerably lower values; accordingly, these data were rejected. All hypothalamic and cerebral specimens in which sufficient GnRH was detected exhibited dose-response slopes parallel to that of synthetic GnRH. Furthermore, the immunoreactive material from hypothalamic extracts was indistinguishable from synthetic GnRH in its elution pattern on carboxymethylcellulose ion-exchange chromatography and in its mobility during isoelectric focusing. Prior to 11 weeks of fetal age, the hypothalamic content of GnRH was low (<1 ng) but increased progressively to values ranging from 2.4 to 6.8 ng between 14 and 17.5 weeks. No sex difference was observed. The parallelism between this rise in hypothalamic GnRH content and previously reported changes in pituitary and serum gonadotropin concentrations in the human fetus suggests that the anterior pituitary may be under hypothalamic regulation from its inception. The absence of a sex difference in hypothalamic GnRH content despite clearly higher circulating FSH and LH levels in females vs males at comparable ages suggests that the putative fetal testicular gonadotropin feedback inhibitor is operative at the pituitary rather than at the hypothalamic level.