Mu Opioid Receptor Regulation of Gonadotropin-Releasing Hormone-Luteinizing Hormone Axis during Short-Term Food Deprivation: Role of Alpha1-Adrenoreceptor Signaling.

  Vol. 39 (5) 2018 Neuro endocrinology letters Journal Article   2018; 39(5): 363-370 PubMed PMID:  30664341    Citation

OBJECTIVES: Brain bio-energetic stability is required for optimal gonadal steroid positive-feedback activation of the gonadotropin-releasing hormone-I (GnRH-I)-pituitary luteinizing hormone (LH) neuroendocrine axis. Caudal hindbrain metabolic-sensory noradrenergic neurons counter energy deficiency by curtailing the mid-cycle LH surge. Central mu opioid receptors (mu-R) impose inhibitory effects of diverse physiological stimuli, including stress, on LH. DESIGN/MATERIAL AND METHODS: To address the premise that mu-R attenuate the LH surge due to metabolic stress of food deprivation (FD), this study examined impacts of lateral ventricular administration of the selective mu-R antagonist CTOP on FD-associated patterns of GnRH-I protein expression and LH release in estradiol-primed ovariectomized female rats. RESULTS: FD caused CTOP-reversible reductions in circulating LH and in micropunch-dissected neural tissue GnRH-I and upstream neurotransmitter (kisspeptin)/biosynthetic enzyme (neuronal nitric oxide synthase) protein content. FD up-regulated mu-R protein expression in reproduction-relevant preoptic structures, e.g. anteroventral periventricular (AVPV) and medial preoptic (MPN) nuclei, responses that were abolished by the alpha1-adrenergic receptor (α1A-R) inverse agonist prazosin. CONCLUSIONS: Current data implicate mu-R in FD attenuation of the E positive-feedback - induced LH surge. Results imply that FD-triggered noradrenergic input to the GnRH-I/LH axis acts in part to enhance reproductive neuroendocrine sensitivity to mu-R inhibition. Further studies are needed to characterize the neurochemical phenotype of AVPV and MPN neurons that express α1A- and/or mu-R, and to determine how these cells are organized within regulatory pathways to impose FD restraint of GnRH-1.