title: Role of endogenous opiates in glucoprivic inhibition of the luteinizing hormone surge and fos expression by preoptic gonadotropin-releasing hormone neurones in ovariectomized steroid-primed female rats.
abstract: In female mammals, the preovulatory luteinizing hormone (LH) 'surge' elicits ovulation and the subsequent transformation of Graafian follicles into corpora lutea, and is thus a critical component of successful reproduction. In light of evidence that this surge is impaired as a consequence of caloric restriction, the following experiments utilized pharmacological strategies to determine whether glucose substrate homeostasis influences the magnitude and/or duration of this pivotal hormonal event. Groups of oestrogen-and progesterone-primed ovariectomized (OVX) rats were injected intravenously (i.v.) with the glucose antimetabolite, 2-deoxy-D-glucose (2DG: 100 or 400 mg/kg), or the vehicle, saline, prior to onset of the expected LH surge. Other rats were pretreated with 2DG (100 microg/rat) or saline by an intracerebroventricular (i.c.v) route. While glucoprivation did not abolish the afternoon LH surge in these animals, mean plasma LH levels were significantly decreased in groups injected with the higher i.v. dose of 2DG or treated with this drug by an i.c.v route, relative to their vehicle-injected controls. In other studies, i.c.v delivery of the opioid receptor antagonist, naltrexone (NALT), partially reversed the inhibitory effects of 2DG on the gonadal steroid-induced LH surge. Dual-label immunocytochemistry of tissue sections from the preoptic area and anterior hypothalamus of OVX, steroid-primed rats revealed nuclear Fos-immunoreactivity (-ir) in a subpopulation of gonadotropin-releasing hormone-(GnRH-)immunopositive neurones prior to maximal preovulatory LH release. Animals pretreated with 2DG i.c.v showed a significant decrease in mean numbers of GnRH neurones exhibiting Fos-ir, whereas coadministration of 2DG and NALT 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 imbalance, 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 steroid positive feedback. The present results also support a role for central opiatergic neurotransmission in glucoprivic regulation of cyclic LH secretion in this animal model.
authors.affiliation: Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, College of Veterinary Medicine, Washington State University, Pullman 99164-6520, USA. kpb@vetmed.wsu.edu
authors.forename: K P
authors.initials: KP
authors.lastname: Briski
authors.forename: P W
authors.initials: PW
authors.lastname: Sylvester
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos / Q000502:physiology*; D005947:Glucose / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D011301:Preoptic Area / Q000166:cytology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004723:Endorphins; D004967:Estrogens; D016760:Proto-Oncogene Proteins c-fos; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005947:Glucose