Norepinephrine suppresses gonadotropin-releasing hormone neuron excitability in the adult mouse.
Norepinephrine (NE) is considered to exert an important modulatory influence upon the activity of GnRH neurons. In the present study, we used a transgenic GnRH-green fluorescent protein mouse model to examine the effects of NE on the electrical excitability of GnRH neurons in male and female mice. Gramicidin-perforated patch recordings demonstrated that NE (10-100 mum) exerted a robust membrane hyperpolarization, with associated suppression of firing, in more than 85% of male prepubertal and adult GnRH neurons (n = 25). The same hyperpolarizing action was observed in female GnRH neurons from diestrous (91%, n = 11), proestrous (50%, n = 14), estrous (77%, n = 13), and ovariectomized (82%, n = 11) mice. A subpopulation (<10%) of silent GnRH neurons in all groups responded to NE with hyperpolarization followed by the initiation of firing upon NE washout. The hyperpolarizing actions of NE were mimicked by alpha1-adrenergic (phenylephrine) and beta-adrenergic (isoproterenol) receptor agonists, but alpha2 receptor activation (guanabenz) had no effect. Approximately 75% of the NE-evoked hyperpolarization was blocked by the alpha1 receptor antagonist prazosin, and 75% of GnRH neurons responded to both phenylephrine and isoproterenol. These findings indicate that NE acts through both alpha1- and beta-adrenergic receptors located on the soma/dendrites of GnRH neurons to directly suppress their excitability throughout the estrous cycle and after ovariectomy. These data force a reanalysis of existing models explaining the effects of NE on gonadotropin secretion.
Han
Seong-Kyu
SK
Department of Oral Physiology and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju 561-756, South Korea.
Herbison
Allan E
AE
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004031:Diestrus / Q000378:metabolism; D004594:Electrophysiology; D004971:Estrus / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000502:physiology*; D010052:Ovariectomy; D018408:Patch-Clamp Techniques; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011359:Proestrus / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D007987:Gonadotropin-Releasing Hormone; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin