Release of Norepinephrine in the Preoptic Area Activates Anteroventral Periventricular Nucleus Neurons and Stimulates the Surge of Luteinizing Hormone

Abstract

The role of norepinephrine (NE) in regulation of LH is still controversial. We investigated the role played by NE in the positive feedback of estradiol and progesterone. Ovarian-steroid control over NE release in the preoptic area (POA) was determined using microdialysis. Compared with ovariectomized (OVX) rats, estradiol-treated OVX (OVX+E) rats displayed lower release of NE in the morning but increased release coincident with the afternoon surge of LH. OVX rats treated with estradiol and progesterone (OVX+EP) exhibited markedly greater NE release than OVX+E rats, and amplification of the LH surge. The effect of NE on LH secretion was confirmed using reverse microdialysis. The LH surge and c-Fos expression in anteroventral periventricular nucleus neurons were significantly increased in OVX+E rats dialyzed with 100 nm NE in the POA. After Fluoro-Gold injection in the POA, c-Fos expression in Fluoro-Gold/tyrosine hydroxylase-immunoreactive neurons increased during the afternoon in the A2 of both OVX+E and OVX+EP rats, in the locus coeruleus (LC) of OVX+EP rats, but was unchanged in the A1. The selective lesion of LC terminals, by intracerebroventricular N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, reduced the surge of LH in OVX+EP but not in OVX+E rats. Thus, estradiol and progesterone activate A2 and LC neurons, respectively, and this is associated with the increased release of NE in the POA and the magnitude of the LH surge. NE stimulates LH secretion, at least in part, through activation of anteroventral periventricular neurons. These findings contribute to elucidation of the role played by NE during the positive feedback of ovarian steroids.

Polycystic ovary syndrome and circulating inflammatory markers

“…Raphael et al also in 2013, reported that the stimulatory effect of NA on the release of gonadotropin-releasing hormone occurs during the positive feedback of ovarian steroids (38). Estrogen up-regulates NA release in the Medio basal hypothalamus.…”

Role of dorsal vagal complex A2 noradrenergic neurons in hindbrain glucoprivic inhibition of the luteinizing hormone surge in the steroid-primed ovariectomized female rat: Effects of 5-thioglucose on A2 functional biomarker and AMPK activity

“…Brainstem noradrenergic innervation of the preoptic area is derived from A1 and A2 cell groups [Fernandez-Galaz et al, 1994]. Disruption of A2 input to the preoptic area is likely to impair the LH surge as preoptic-projecting A2, but not A1 neurons undergo transcriptional activation in response to steroid positive-feedback [Szawka et al, 2013]. The present work documents changes in genomic activity in A2, but not A1 cells after CV4 glucose anti-metabolite administration to steroid-primed OVX female rats, suggesting that hindbrain glucoprivic modifications in NE input to preoptic and other projection sites, after onset of the LH surge, involve adjustments in A2 signaling.…”

“…NE release into the medial preoptic area is causally related to expression of the LH surge [Honma and Wuttke, 1980; Demling et al, 1985; Mohankumar et al, 1994; Szawka et al, 2013]. Here, an alpha 1 -adrenergic receptor agonist pretreatment strategy was used to determine if diminished receptor activation in this site is germane to hindbrain glucoprivic repression of the GnRH-pituitary LH axis.…”

“…Fos, a reliable marker for transcriptional activation, and the glucoprivic-sensitive catecholamine biosynthetic enzyme, dopamine-β-hydroxylase (DβH). NE acts within the medial preoptic area to mediate steroid feedback regulation of LH; indeed, divergent estrogen negative- and positive-feedback actions on this hormone are achieved, in part, by corresponding patterns of basal versus elevated NE release into that area [Demling et al, 1985; Mohankumar et al, 1994; Szawka et al, 2013]. The current studies examined the premise that hindbrain glucoprivic suppression of the LH surge involves diminished preoptic NE release.…”

Hindbrain estrogen receptor-beta antagonism normalizes reproductive and counter-regulatory hormone secretion in hypoglycemic steroid-primed ovariectomized female rats

“…A2 neurons mediate estrogen negative- and positive-feedback regulation of LH secretion, responding to these dualistic signals by release of norepinephrine into the medial preoptic area at basal versus elevated rates [Demling et al, 1985; Mohankumar et al, 1994; Szawka et al, 2013]. Metabolic restraint of the LH surge involves diminished hindbrain NE signaling to the preoptic AVPV, as administration of the alpha-adrenergic receptor agonist methoxamine to that site reverses hindbrain glucoprivic suppression of GnRH neuron Fos immuno-labeling and pituitary LH release [Ibrahim and Briski, 2014].…”