ROLE OF ENDOGENOUS OPIATES IN GLUCOPRIVIC INHIBITION OF THE LUTEINIZING-HORMONE SURGE AND FOS EXPRESSION BY PREOPTIC GONADOTROPIN-RELEASING-HORMONE NEURONS IN OVARIECTOMIZED STEROID-PRIMED FEMALE RATS

In female mammals, the preovulatory luteinizing hormone (LH) 'surge' e licits ovulation and the subsequent transformation of Graafian follicl es into corpora lutea, and is thus a critical component of successful reproduction. In light of evidence that this surge is impaired as a co nsequence of caloric restriction, the following experiments utilized p harmacological strategies to determine whether glucose substrate homeo stasis influences the magnitude and/or duration of this pivotal hormon al event. Groups of oestrogen-and progesterone-primed ovariectomized ( OVX) rats were injected intravenously (i.v.) with the glucose antimeta bolite, 2-deoxy-D-glucose (2DG: 100 or 400 mg/kg), or the vehicle, sal ine, prior to onset of the expected LH surge. Other rats were pretreat ed with 2DG (100 mu g/rat) or saline by an intracerebroventricular (i. c.v) route. While glucoprivation did not abolish the afternoon LH surg e in these animals, mean plasma LH levels were significantly decreased in groups injected with the higher i.v. dose of 2DG or treated with t his drug by an i.c.v route, relative to their vehicle-injected control s. In other studies, i.c.v delivery of the opioid receptor antagonist, naltrexone (NALT), partially reversed the inhibitory effects of 2DG o n the gonadal steroid-induced LH surge. Dual-label immunocytochemistry of tissue sections from the preoptic area and anterior hypothalamus o f OVX, steroid-primed rats revealed nuclear Fos-immunoreactivity (-ir) in a subpopulation of gonadotropin-releasing hormone-(GnRH-)immunopos itive neurones prior to maximal preovulatory LH release. Animals pretr eated with 2DG i.c.v showed a significant decrease in mean numbers of GnRH neurones exhibiting Fos-ir, whereas coadministration of 2DG and N ALT resulted in numbers of double-labelled neurones that were similar to those detected in the non-drug-treated controls. These studies show that magnitude of the LH surge is decreased by glucose substrate imba lance, and that regulatory effects of this metabolic challenge on the reproductive neuroendocrine axis is correlated with alterations in the transcriptional activation of preoptic GnRH neurones by gonadal stero id positive feedback. The present results also support a role for cent ral opiatergic neurotransmission in glucoprivic regulation of cyclic L H secretion in this animal model.