Disruption of GnRH Pulses by Anti-GnRH Serum and Phentolamine Obliterates Pulsatile LH but not FSH Secretion in Ovariectomized Rabbits

Abstract

It has been hypothesized that the secretion of gonadotropins, i.e. luteinizing hormone (LH) and follicle-stimulating hormone (FSH), is driven by a synchronized neural network (‘pulse generator’). This network, regulated in part by α-adrenergic activity, ultimately generates bursts of hypothalamic gonadotropin-releasing hormone (GnRH) release. In this study, we used the push-pull (PP) perfusion technique in ovariectomized rabbits to investigate three aspects of the (‘GnRH/gonadotropin pulse generator’) hypothesis. The objectives were to determine: (1) if plasma LH and FSH pulses occur concomitantly with mediobasal hypothalamic (MBH-) GnRH pulses, (2) changes in the patterns of pulsatile LH and FSH secretion when pulsatile MBH GnRH signals are interrupted by either local immunoneutralization of GnRH or intravenous infusion of the α-adrenergic antagonist phentolamine (PHEN, 4 mg/kg BW), and (3) whether third cerebroventricular (3VT-) GnRH patterns reflect neuronal GnRH release from the MBH. We found that while both plasma LH and FSH patterns were pulsatile, MBH GnRH pulses were significantly coupled only with LH pulses (94% coincidence). Both the local immunoneutralization of MBH GnRH pulses and the PHEN-induced suppression of MBH GnRH pulses obliterated the pulsatile secretion of LH, but not FSH. Neither MBH GnRH nor plasma LH or plasma FSH pulses were concurrent with 3VTGnRH pulses. However, the PP perfusion of the 3VT appeared to alter the pulsatile release of MBH GnRH and pituitary LH. The results support the hypothesis that in the absence of ovarian signals, the ‘pulse generator’ is maintained by tonic α-adrenergic input and that a ‘cellular unity’ of MBH GnRH release (GnRH pulses) drives the gonadotrophs to secrete LH in pulses. In contrast, the pulsatile release of FSH appears to involve additional nonovarian regulatory events to those controlling LH secretion.

Is there an FSH-releasing factor?

“…Pau et al (1991) , 1997). Although pulses in peripheral circulation are not as discrete and visually identifiable as they are in hypophyseal portal circulation, peripheral pulses identified using pulse detection algorithms were used to assess these relationships.…”

“…Evidence that gonadally derived inhibin is involved in selectively suppressing overall FSH production (McNeilly, 1988;Ying 1988;Baird et al, 1991) is also very strong. Although the effects of these long-range endocrine regulators in altering the baseline concentration of FSH is uncontested, they do not provide an explanation for the occurrence of discordant LH and FSH pulses in gonadectomized animals (Culler and Negro-Vilar, 1987;Pau et al, 1991;.…”

Evidence that lamprey GnRH-III does not release FSH selectively in cattle

“…However, secretion of FSH is less dependent upon GnRH control and is instead regulated largely by GnRH-independent factors that include gonadal activins, inhibins and follistatins (Clarke et al 1983, Pau et al 1991, Kovacs et al 1993.…”

Protein and mRNA expression of gonadotropin-releasing hormone receptor in yaks during estrus

“…Simultaneously, GnRH and neighboring GnRH neurons stimulate the secretion of LH (Conn et al, 1995;Sealfon et al, 1997). However, the secretion of FSH is less dependent upon GnRH and is instead regulated largely by GnRH-independent factors, including gonadal activins, inhibins, and follistatins (Clarke et al, 1983, Pau et al, 1991, Kovacs et al, 1993. Gonadotropin-releasing hormone-III may act as a weak competitor for the mammalian GnRHR, which does not support the hypothesis that it selectively regulates the release of FSH in cattle (Amstalden et al, 2004).…”