Down-regulation of gonadotropin release by the ovine fetal pituitary gland by the superagonist D-Trp6pro9NET-LRF

Abstract

D-Trp6Pro9NET-LRF (Trp6-LRF) a superagonist analogue of LRF has caused suppression of gonadotropin secretion when administered chronically in animals and in humans, but has not been studied in the fetus. In 3 chronically catheterized ovine fetuses ages 105-130 days (term 147±3), spontaneous LH pulses of 3-8 ng/ml occurred every 3-4 hrs with baseline levels of less than 1 ng/ml. FSH levels ranged from 4-8 ng/ml and did not vary with the LH discharge. Administration of 5 μg synthetic LRF IV produced a mean incremental increase (Δ) of LH of 6.8 ng/ml (range 5.8-7.7 ng/ml), while the mean Δ of FSH was 1.9 ng/ml (0.9-2.9 ng/ml). After the first 10 μg dose of Trp6-LRF IV, the mean Δ of LH was 16.4 ng/ml (4.9-25.6 ng/ml), and the mean Δ of FSH was 3.9 ng/ml (2.9-4.7 ng/ml). Elevated levels of LH and FSH were sustained for 2 hrs after the agonist. A second 10 μg dose given 24 hrs later did not induce a significant rise in LH or FSH. Intravenous LRF elicited a minimal rise in LH and FSH during a 2-14 day study period, without measurable LH pulses. The findings are consistent with an initial phase in which Trp6-LRF stimulates FSH and LH release followed by a prolonged phase of refractoriness to either LRF or the LRF agonist. The later effect is consistent with down-regulation of fetal pituitary LRF receptors. These observations provide further support for the influence of endogenous fetal LRF on fetal gonadotropin secretion and of neuroendocrine control mediated by LRF as early as 105 days of gestation.