Effects of estradiol on number and distribution of central estrogen receptor in female rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 142-166-Hypothalamus-Pituitary Development & Biology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-160
Xian Liu*1, Minqian Shen2, Zheng Zhu2 and Haifei Shi2
1Miami Univ, Oxford, OH, 2Miami University, Oxford, OH
Sex hormone estrogen plays pivotal roles in the regulation of sexual behavior as well as energy balance and body weight by interacting with estrogen receptors (ERs). However, how estrogen regulates its receptors in the central nervous system (CNS) is unclear. Estradiol (E2) has been shown to affect ERα despite the results remains controversial. Some studies reported that female rats with higher endogenous E2 levels expressed greater amount of estrogen receptors than male rats with lower endogenous E2 levels. In addition, female rats expressed a greater amount of ERα during proestrous phase when E2 peaks, than during diestrous phase when E2 reaches nadir (1). These results suggest that E2 at physiological level up-regulates ERa. When E2 is decreased by ovariectomy (OVX) and is replaced by hormone replacement therapy, the change of ERa has been inconsistently reported. Some earlier studies in 1990’s reported down-regulation (2-5), whereas more recent studies reported up-regulation (6) of ERa by E2 replacement following OVX. The inconsistency of these studies may be caused by different timelines and different methods used for E2 replacement following OVX surgery. A recent in vitro study directly examined E2’s influence on ERa expression in primary dissociated cultures of neurons isolated from the ventromedial hypothalamic nucleus (VMH) of female rats. This study revealed that both supra-physiological and physiological concentrations of E2 increased the expression of ERa (7).

In this study, cyclic treatment of E2 at a physiological dose (2 µg 17β E2, one injection every 4 days), which mimics the endogenous fluctuations of E2 (8), was used to investigate whether or not physiological level of E2 regulates the distribution and quantity of ERa in the hypothalamus, including the medial preoptic area (MPA) and periventricular nucleus (Pe) related to sexual behavior and HPG axis, the arcuate (ARC) and VMH nuclei related to food intake, and paraventricular nucleus (PVN) related to energy expenditure.  Immunohistochemistry was used to visualize ERα quantity and distribution in OVX rats with cyclic vehicle oil (OVX+Oil) or E2 (OVX+E2) replacement. OVX+Oil rats expressed a greater number of ERa at MPA, and showed a slight increase of ERa at ARC and VMH, compared to OVX+E2 rats.  Additionally, OVX+Oil and OVX+E2 rats had similar numbers of ERa at PVN and Pe. In conclusion, physiological E2 regulates ERα differentially among various neuronal groups in the CNS.

(1) Shughrue PJ, Bushnell CD, Dorsa DM (1992). Endocrinology 131:381–388. (2) Koch M (1990).  Neuroendocrinology 51:505–514. (3) Lauber AH, Romano GJ, Mobbs CV, Pfaff DW (1990). J Neuroendocrinol 2:605–611. (4) Lauber AH, Mobbs CV, Muramatsu M, Pfaff DW (1991). Endocrinology 129:3180–3186. (5) Simerly RB, Young BJ (1991). Mol Endocrinol 5:424–432. (6) Devidze N, Mong JA, Jasnow AM, Kow LM, Pfaff DW (2005) Proc Natl Acad Sci USA 102:14446–14451. (7) Malikov V, Madeira M.D. (2013). Neurochemical Research. 38:82-9. (8) Asarian L and Geary N (2002). Horm Behav 42(4): 461-471.

Nothing to Disclose: XL, MS, ZZ, HS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH R15 DK090823 to HS