Differential Expression of Estrogen Receptor-β and Estrogen Receptor-α in the Rat Ovary

Abstract

Immunohistochemical localization of two estrogen receptor (ER) subtypes, ER beta and ER alpha, was performed in neonatal, early postnatal, immature, and adult rats to determine whether ER alpha and ER beta are differentially expressed in the ovary. ER beta and ER alpha were visualized using a polyclonal anti-ER beta antibody and a monoclonal ER alpha (ID5) antibody, respectively. Postfixed frozen sections and antigen-retrieved paraffin sections of the ovary revealed nuclear ER beta immunoreactivity (IR) in granulosa cells, which was prevented when peptide-adsorbed antibody was used instead. In immature and adult rat ovaries, ER beta was expressed exclusively in nuclei of granulosa cells of primary, secondary, and mature follicles. Atretic follicle granulosa cells showed only weak or no staining. No specific nuclear ER beta IR was detected in thecal cells, luteal cells, interstitial cells, germinal epithelium, or oocytes. In neonatal rat ovary, no ER beta expression was found. In ovaries of 5- and 10-day-old rats, weak ER beta IR was observed in granulosa cells of primary and secondary follicles, but no staining was detected in the primordial follicles. ER alpha protein exhibited a differential distribution in the ovary with no detectable expression in the granulosa cells but evidence of ER alpha IR in germinal epithelium, interstitial cells, and thecal cells. In the oviduct and uterus, IR for ER alpha, but not ER beta, was found in luminal epithelium, stromal cells, muscle cells, and gland cells. Our present study demonstrates that ER beta and ER alpha proteins are expressed in distinctly different cell types in the ovary. The exclusive presence of ER beta in granulosa cells implies that this specific new subtype of ER beta mediates some effects of estrogen action in the regulation of growth and maturation of ovarian follicles.

The transcriptome of human oocytes

“…Genes significantly up-regulated in this pathway were CTBP2, ESR1, GTF2H1, GTF2H2, MAP2K1, NCOA1, NCOA3, PCQAP, PHB2, POLR2C, POLR2J, RBM9, TAF3, TAF4 and 4B, TAF5, TAF6, TAF12, and TBP. Recent studies in knockout models for aromatase have shown that estrogen is not required for the generation of preimplantation embryos (34); our study, however, in agreement with previous reports (35,36) suggests that some genes associated with the ER pathways are indeed transcribed in the oocyte, perhaps in response to hormonal stimulation during folliculogenesis and oocyte maturation. It remains to be determined whether the ER pathway has a role during preimplantation development in human embryos.…”

Ovarian wedge resection restores fertility in estrogen receptor β knockout (ERβ −/− ) mice

“…S oon after the discovery of estrogen receptor ␤ (ER␤) in 1996 (1), Sar and Welsch (2) showed that there is high expression of ER␤ in the nuclei of granulosa cells and suggested that ER␤ mediates some effects of estrogen action in the regulation of growth and maturation of ovarian follicles. Studies on mice that do not synthesize estrogen (aromatase knockout mice) have revealed that estrogen is essential for ovulation (3) but not for granulosa cell proliferation.…”

The effects of ethylene glycol monomethyl ether on female reproductive system in juvenile rats

“…During the juvenile to pubertal stages, HPG axis are central to the dramatic neuroendocrine changes in the process of maturation, including changes in E 2 positive/negative feedback system and gonadotropin and their receptor levels (Picut et al, 2015). The difference in the effects of EGME among juvenile, pubertal, and mature rats is possibly due to the differential effects of EGME on the HPG axis or the difference in the sensitivity or regulation of the hormonal effects of E 2 or P4 on the reproductive organs during sexual maturation, with the complication of secondary effect of growth retardation and delay in the onset of puberty (Ohta et al, 1996;Picut et al, 2015;Sar and Welsch, 1999). The highest dose, at 300 mg/kg of EGME, showed severe growth retardation with more than 30% lower body weight compared to controls as well as significant delay in puberty onset, and disruption of estrous cycle.…”