Classical Estrogen Receptors and ERα Splice Variants in the Mouse

Abstract

Estrogens exert a variety of effects in both reproductive and non-reproductive tissues. With the discovery of ERα splice variants, prior assumptions concerning tissue-specific estrogen signaling need to be re-evaluated. Accordingly, we sought to determine the expression of the classical estrogen receptors and ERα splice variants across reproductive and non-reproductive tissues of male and female mice. Western blotting revealed that the full-length ERα66 was mainly present in female reproductive tissues but was also found in non-reproductive tissues at lower levels. ERα46 was most highly expressed in the heart of both sexes. ERα36 was highly expressed in the kidneys and liver of female mice but not in the kidneys of males. ERβ was most abundant in non-reproductive tissues and in the ovaries. Because the kidney has been reported to be the most estrogenic non-reproductive organ, we sought to elucidate ER renal expression and localization. Immunofluorescence studies revealed ERα66 in the vasculature and the glomerulus. It was also found in the brush border of the proximal tubule and in the cortical collecting duct of female mice. ERα36 was evident in mesangial cells and tubular epithelial cells of both sexes, as well as podocytes of females but not males. ERβ was found primarily in the podocytes in female mice but was also present in the mesangial cells in both sexes. Within the renal cortex, ERα46 and ERα36 were mainly located in the membrane fraction although they were also present in the cytosolic fraction. Given the variability of expression patterns demonstrated herein, identification of the specific estrogen receptors expressed in a tissue is necessary for interpreting estrogenic effects. As this study revealed expression of the ERα splice variants at multiple sites within the kidney, further studies are warranted in order to elucidate the contribution of these receptors to renal estrogen responsiveness.

Complete knockout of estrogen receptor alpha is not directly protective in murine lupus

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Sex‐dependent differences in renal angiotensinogen as an early marker of diabetic nephropathy

“…renal anti-fibrotic effect was observed after inhibition of estradiol synthesis and not androgen receptor blockade may suggest that estrogen receptors localized in the mesangial cells of males (Irsik et al, 2013) may contribute to this effect. This appears to be in contrast to the renoprotective effects of estradiol in diabetic renal disease in females (Mankhey et al, 2005).…”

The Expanding Complexity of Estrogen Receptor Signaling in the Cardiovascular System

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