Expression of Estrogen Receptor-α and cFos in Norepinephrine and Epinephrine Neurons of Young and Middle-Aged Rats during the Steroid-Induced Luteinizing Hormone Surge

Abstract

Norepinephrine (NE) and epinephrine are important stimulators of GnRH release during the preovulatory surge in female rats. Previous studies have shown that the catecholaminergic neurons are sensitive to estradiol and that NE release in the hypothalamus is decreased in middle-aged rats at the time when the estrous cycles become irregular and later cease to exist. The aims of the present study were to determine whether the NE and epinephrine neurons continue to express estrogen receptor (ER)-alpha in middle-aged rats; temporal expression of ER-alpha and cFos changes with age during the steroid-induced surge; and tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanol-N-methyltransferase mRNA content in catecholaminergic neurons of the brain stem changes during the surge with age. The results show that there was no difference in TH mRNA content; however, DBH mRNA levels in areas A1, A2, and C1 of the middle-aged animals did not rise during the surge as was observed in the young animals. Although the percentage of NE and epinephrine neurons that express ER-alpha was unchanged during the surge in both young and middle-aged animals, cFos expression was enhanced in areas A1 and A2 of the middle-aged animals but not in the young animals. Together the results suggest that NE and epinephrine neurons in the middle-aged rat continue to express appropriate basal levels of TH, DBH, and phenylethanol-N-methyltransferase mRNAs as well as ER-alpha and cFos; however, the enhancement of DBH expression, as seen in the young animals during the steroid-induced surge, was not detected in middle-aged animals. On the other hand, cFos expression in the middle-aged rat was higher in areas A1 and A2 during the surge. It is concluded that the reduced catecholamine release during the surge in middle-aged rats is caused, in part, by an altered sensitivity of the NE neurons to estradiol, which results in an aberrant cFos expression and probably not by major deficits in the expression of transmitter synthesizing enzymes or steroid receptors.

Short term treatment with estradiol decreases the rate of newly generated cells in the subventricular zone and main olfactory bulb of adult female mice

“…Surprisingly, no estradiol receptors (ER␣ or ER␤) are found in the SVZ in mice (Mitra et al, 2003;Merchenthaler et al, 2004) although Isgor and Watson (2005) showed that Ki-67-immunoreactive cells of the SVZ expressed estrogen receptor alpha mRNA in rats. We thus suggest that estradiol most likely modulates cell proliferation by indirect pathways projecting to the SVZ such as dopamine ␤-hydroxylase (DBH) or tyrosine hydroxylase (TH) neurons which are estradiol-sensitive (Temel et al, 2002;Kishi et al, 2005) or by GPR30 which are membrane receptors binding estradiol (Bologa et al, 2006). Several reports suggested that GPR30 might be a G-protein coupled estrogen receptor mediating nongenomic effects of estradiol but its brain localization and its exact role remain still unknown (Micevych and Dominguez, 2009;).…”

Ovarian function and reproductive senescence in the rat: role of ovarian sympathetic innervation

“…In relation to this, GnRH pulses and hence, LH secretion, are attenuated in middle-aged rats (8-12-month-old) (Rubin 2000). In addition, the central response to the steroidinduced LH peak in middle-aged rats is also attenuated in comparison to young rats (Gee et al 1984, Wise 1984, Rubin 2000, Temel et al 2002. Interestingly, oestrogens cause epigenetic modifications, switching the Kiss1 promoter to an active form, resulting in an increase in AVPV-specific Kiss1 gene expression (Tomikawa et al 2012).…”

Effects of Estradiol Valerate and Remifemin on Norepinephrine Signaling in the Brain of Ovariectomized Rats

“…DBH-ir fibers and terminals in these nuclei became thinner and had a decreased AOD after OVX, but these changes were attenuated following E 2 administration. It is known that catecholaminergic neurons are sensitive to E 2 , and norepinephrine release in the hypothalamus are decreased in middle-aged rats at the time when the estrous cycles become irregular and later cease to exist [31]. Estrogen has been shown to upregulate norepinephrine release in the mediobasal hypothalamus of OVX rhesus monkeys [32], which is in accordance with our results and indicates that low estrogen was mainly responsible for the decrease of DBH-ir fibers and terminals in the POAH after OVX.…”