Hormone ontogeny in the ovine fetus: XIV. The effect of 17 beta-estradiol infusion on fetal plasma gonadotropins and prolactin and the maturation of sex steroid-dependent negative feedback.

17 beta-Estradiol (E2; 100 micrograms/kg X day) was infused iv for 6 days into three chronically catheterized ovine fetuses beginning at 105-106 days of gestation (term, 147 days) and into four younger fetuses for 3 days commencing at 87-92 days. Control studies were performed on three fetuses at each age. At 90 days, E2 had no effect on the basal concentration of either LH or FSH. In both control and E2-infused fetuses, repeated LHRH testing was associated with a decreased LH response, but the decrease was not greater in the E2-infused fetuses. The FSH response was unaffected in either group. At 105 days, E2 caused suppression of the mean basal concentration of plasma LH from 1.2 +/- 0.1 to 0.1 +/- 0.1 ng/ml (P less than 0.01) and of basal FSH from 5.6 +/- 0.5 to 3.3 +/- 0.6 ng/ml (P less than 0.05). The LH response to LHRH administration (50-micrograms iv bolus) also was suppressed by E2. The maximal incremental LH response fell from 7.1 +/- 0.4 to 3.3 +/- 0.5 ng/ml (P less than 0.01); the integrated response decreased from 5.8 +/- 0.2 to 1.8 +/- 0.2 ng/ml X h (P less than 0.01). However, no effect was observed on the rise in FSH concentration evoked by LHRH. In control studies at 105 days, basal and LHRH-stimulated gonadotropin concentrations remained constant during the experiment. These results indicate that the capacity for exogenous E2 to suppress fetal pituitary gonadotropin secretion in the ovine fetus develops between 90 and 105 days of gestation, before the normal ontogenic decrease both in the basal concentration of fetal pituitary gonadotropins and in LHRH-stimulated FSH and LH secretion, which occur later in gestation. We suggest that the development of the E2-sensitive negative feedback mechanism in the fetal hypothalamic-pituitary unit is a major factor in this decrease. At 90 days gestational age, the mean fetal plasma concentration of PRL was not affected by the infusion of E2 into the fetus (5.9 +/- 1.5 ng/ml before E2 infusion 8.1 +/- 3.2 ng/ml during E2 infusion). However, at 105 days, the mean PRL concentration rose from 49.3 +/- 18.2 to 101.6 +/- 26.1 ng/ml (P less than 0.01) after the infusion of E2. The capacity for E2 to stimulate PRL release develops in parallel with the rise in fetal plasma PRL and estrogen concentrations. The results provide evidence that circulating estrogens are a determinant of fetal PRL concentrations in late gestation.