The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input

Endocrinology. 2016 Jan;157(1):323-35. doi: 10.1210/en.2015-1323. Epub 2015 Nov 10.

Abstract

In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / agonists
  • ARNTL Transcription Factors / antagonists & inhibitors
  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism
  • Adrenergic alpha-1 Receptor Antagonists / pharmacology
  • Animals
  • Estradiol / pharmacology
  • Estrogen Replacement Therapy
  • Female
  • Follicular Phase / drug effects
  • Gene Expression Regulation* / drug effects
  • Kisspeptins / agonists*
  • Kisspeptins / antagonists & inhibitors
  • Kisspeptins / genetics
  • Kisspeptins / metabolism
  • Luteinizing Hormone / metabolism*
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Norepinephrine / metabolism*
  • Ovariectomy / adverse effects
  • Period Circadian Proteins / agonists
  • Period Circadian Proteins / antagonists & inhibitors
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism
  • Prazosin / pharmacology
  • Preoptic Area / drug effects
  • Preoptic Area / metabolism*
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / chemistry
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Signal Transduction / drug effects
  • Synaptic Transmission / drug effects
  • Up-Regulation* / drug effects

Substances

  • ARNTL Transcription Factors
  • Adrenergic alpha-1 Receptor Antagonists
  • Arntl protein, rat
  • Kiss1 protein, rat
  • Kisspeptins
  • Nerve Tissue Proteins
  • Per1 protein, rat
  • Period Circadian Proteins
  • Receptors, Adrenergic, alpha-1
  • Estradiol
  • Luteinizing Hormone
  • Norepinephrine
  • Prazosin