Inhibition of Hypothalamic Gonadotropin-Releasing Hormone Release by Endogenous Opioid Peptides in the Female Rabbit

Abstract

Recent evidence suggests that the endogenous opioid peptides (EOPs) inhibit luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by suppression of hypothalamic gonadotropin-releasing hormone (GnRH) release, and that the feedback inhibition by EOPs is influenced by ovarian steroids. In the present studies, intact (INT) and ovariectomized (OVX) adult female rabbits were fitted with femoral vein catheters and mediobasal hypothalamic (MBH) push-pull perfusion (PPP) cannulae. One week after brain cannulation, does were subjected to 6 h of PPP and sequential blood sampling. In experiment I, INT (n = 6) and OVX (n = 5) does were infused intravenously with saline for 4 h followed by 2 h of infusion of the opiate antagonist naloxone (NAL; 10 µg/min/kg) while the MBH was simultaneously perfused with media. In experiment II, INT (n = 5) and OVX (n = 5) does were perfused with media for 4 h followed by 2 h of intrahypothalamic (IHP) NAL perfusion (0.2 µg/min). The GnRH in push-pull perfusates and LH and FSH in plasma samples collected at 10-min intervals were measured by specific radioimmunoassays. In INT does, neither intravenous infusion nor IHP perfusion of NAL altered pulsatile parameters of GnRH or LH release. In contrast, both intravenous and IHP NAL administration stimulated GnRH and LH release within 30–50 min in OVX does by marked increases in both GnRH and LH pulse amplitudes. Neither route of NAL administration affected FSH secretion in any of the treatment groups. We conclude that (1) EOPs are involved in the inhibition of hypothalamic GnRH secretion in OVX does; (2) the feedback inhibition by ovarian steroids on the hypothalamic-pituitary axis in the rabbit is sufficient to compromise the effects of EOPs, and (3) under these experimental conditions, the hypothalamic mechanisms which regulate the secretion of pituitary LH and FSH may be independent.

Neuroendocrine Regulation of GnRH Release in Induced Ovulators

“…Female rabbits showed a dramatic rise in LH pulse amplitudes and mean LH levels when given an intravenous infusion of naloxone 2 weeks after gonadectomy. However, no LH response to naloxone was obtained in female rabbits that were gonadally intact and in estrus (163). In another study (250), naloxone effectively raised LH pulse amplitudes in female rabbits tested after ovariectomy.…”

“…Chronic treatment with morphine blocked GnRH secretion (42) and decreased POA GnRH mRNA levels (133), whereas the opioid receptor antagonist naloxone increased plasma LH levels and POA GnRH mRNA levels. Several studies suggest that endogenous opioids inhibit LH secretion in rabbits (163,250), ferrets (120), and cats (101). Female rabbits showed a dramatic rise in LH pulse amplitudes and mean LH levels when given an intravenous infusion of naloxone 2 weeks after gonadectomy.…”

Effects of Neuropeptide Y on the in vitro Release of Gonadotropin-Releasing Hormone, Luteinizing Hormone, and Beta-Endorphin and Pituitary Responsiveness to Gonadotropin-Releasing Hormone in Female Macaques

“…Some of these regions, particularly the anterior and mediobasal hypo- thalamic (AH and MBH) areas are also rich in neural cell bodies and fibers containing gonadotropin-releasing hormone (GnRH) [7], endogenous opioid peptides (EOP) [8] and cate cholamines (CA) [9], A recent study noted NPY-containing ter minals that synapsed upon GnRH cells in the AH of sheep (10]. This regional co-localization of neuronal peptides and neuro transmitters provides the anatomical framework for studies aimed at understanding peptide-neurotransmitter interactions in the regulation of GnRH secretion.Recent findings from our laboratory demonstrate that in the rabbit and monkey, activities of MBH GnRH neurons and pitu itary gonadotropes are modulated directly and/or indirectly by ovarian steroids [11,12], CA [I3, 14], and EOP [15,16]. More over, MBH GnRH and luteinizing hormone (LH) secretions are markedly affected by the in vivo and in vitro administration…”

Acupuncture for Perimenopausal Symptoms in Women who Underwent Oophorectomy – a Comparative Study

“…Quigley et al [46] first reported an increased opioid inhibition of LH secretion in hyperprolactinemic patients with pituitary microadenomas. Ching [47] as well as Orstead and Spics [48] showed that opioid peptides suppress GnRH release in rats and rabbits. The role of these neuropeptides including β-EP in the regulation of GnRH secretion in humans has recently been reviewed by Kalra et al [49] and Pau and Spies [50].…”