Expression of Estrogen Receptor α in the Anteroventral Periventricular Nucleus of Hypogonadal Mice

Abstract

Gonadotropin-releasing hormone-1 (GnRH-1) neurons play critical roles in the development and maintenance of reproductive function in all vertebrates. Due to a truncation in the GnRH-1 gene, hypogonadal (hpg) mice are unable to synthesize GnRH-1 and are Infertile. These animals develop in the complete absence of exposure to gonadal steroid hormones, making them an interesting model for understanding brain sexual differentiation and dimorphism. We studied expression of the estrogen receptors (ERs) α and β in the medial anteroventral periventricular nucleus (mAVPV), an important reproductive neuroendocrine brain region, in wild-type and hpg mice of both sexes. Adult wild-type and hpg mice of the same genetic background were used to quantify numbers of ERα and ERβ immunoreactive cells in the mAVPV using a stereologic approach. Quantitative analyses showed that ERα cell numbers were significantly higher In hpg than wild-type mice, irrespective of sex. Qualitatively, ERα-immunoreactive cells were concentrated more densely along the ventricular zone of the AVPV of wild-type female mice compared with wild-type male mice or hpg male and female mice. No ERβ-immunoreactive cells were detected in the mAVPV of any mice, a result that was surprising because ERβ expression is abundant in the mAVPV of rats. These results on ERα provide additional evidence that the female brain is not the “default” organizational pattern, because neither ERα cell number nor its distribution in hpg mice, which develops with a deficiency of reproductive hormones, resembles that of the wild-type female mouse. Differences in ERα expression may be due in part to the absence of gonadal steroid hormones, although they more likely to also involve othc factors, potentially GnRH itself.