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'

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 0 and peak LH) in oLH (delta oLH) and oFSH (delta oFSH) 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 (delta 4A) were measured in nine male fetuses. After a stimulatory response to the first dose of LRF-A, the mean delta oLH and delta oFSH 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 delta oLH and delta oFSH responses to LRF before and at intervals after LRF-A therapy. In the fetus, the delta oLH and delta oFSH responses remained significantly decreased 7-8 d after the agonist was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneity in the Storage of Gonadotropins in the Ovine Fetus and Evidence for Luteinizing Hormone-Follicle-Stimulating Hormone Cells in the Fetal Pituitary

“…It has been established in the sheep fetus that LH is secreted in a pulsatile manner at least from 81 days of gestation [29]. Moreover, the release of LH is suppressed by an infusion of a GnRH agonist [30] or antagonist at least from 104 days of gestation [31]. Furthermore, the sensitivity of the fetal pituitary to exogenous GnRH is maximal between 115 and 132 days of gestation [32].…”

Acute N-Methyl-<i>D,L</i>-Aspartate Administration Stimulates the Luteinizing Hormone Releasing Hormone Pulse Generator in the Ovine Fetus

“…At this gestational age, the gonadotropin response to exogenous LHRH is less than that during midgestation, when the mean basal plasma concentrations of oLH and oFSH are high [3]. We showed that specific high-affinity LH-RH receptors are present by midgestation in the ovine fetal pituitary and that the high oLH and oFSH plasma values are LH-RH dependent [4]. Hence the fetal hypothalamic LH-RH-pituitary gonadotropin-gonadal system is functional as early as midgestation.…”

“…In the primary pituitary cell culture system, NMDA had no effect on oLH, oFSH, oGH, and oPRL secretion, while LH-RH stimulated both oLH and oFSH. Furthermore, desensitization of the fetal gonadotropes with D -Trp 6 Pro 9 NEt-LH-RH, which suppresses fetal pituitary gonadotropins and the response to exogenous LH-RH [4], completely abolished the oLH and oFSH responses to the administration of NMDA. Neuroexcitatory amino acids also failed to stimulate LH and FSH release when they were incubated with pituitary tissue from adult rats and monkeys [15, 23].…”

“…Furthermore, the ovine fetal pituitary gland is capable of responding to exogenous luteinizing hormone releasing hormone (LH-RH); the maximal increments in oLH and oFSH occur during midgestation when the mean gonadotropin concentration is highest [3]. Chronic LH-RH agonist or acute antagonist treatment leads to desensitization of the fetal gonadotrope and to suppression of pulsatile pituitary gonadotropin release [4, 5]. The factors involved in the physiological control of the gonadotropin secretion in the fetus and of the changes that occur with development are not well understood [6].…”

Neuroendocrine control of the onset of puberty

“…They demonstrated that circulating levels of LH and FSH in male and female fetuses during mid gestation were similar to those observed in castrated adult sheep. Moreover, sequential sampling of the fetal circulation identified distinct episodes of GnRH dependent LH secretion at this stage of fetal development presumable reflecting corresponding discharges of GnRH from the fetal hypothalamus [152] [153]. The latter view is supported by the contemporaneous finding that administration of an iv bolus of the GnRH secretagogue, NMDA (see above) elicited LH discharges from the fetal pituitary [154].…”