Caloric restriction increases ratio of estrogen to androgen receptors expression in murine ovaries--potential therapeutic implications

Abstract

Both estrogens and androgens are involved in the development and normal functioning of the ovaries. It is also known that ovarian function is regulated by diet. The goal of this study was to estimate the expression of sex hormone receptors in ovaries of mice that were on a 9-month caloric restriction (alternate-day feeding) as compared to normal control animals fed ad libitum. We found that prolonged caloric restriction in mouse ovaries led to increased expression of estrogen receptors (ERs) but did not affect expression of the androgen receptor (AR). This increase in ER:AR ration as result of caloric restriction may lead to higher sensitivity to estrogens and upon return to normal diet may increase ovulation. Thus our observation shed more light on a role of beneficial effect of calorie restriction on female reproduction.

Fig. 1

Immunolocalization and immunoexpression of ERs in the ovaries of mice on CR (a, c, e) and in the ovaries of mice fed ad libitum (b, d, f). The high expression of ERs was observed in ovaries of mice on CR in granulosa cells (black arrow), theca cells (red arrow), ovarian surface epithelium cells (black arrowhead), interstitial cells (black asterisk), and endothelial cells (red asterisk) (a, c, e) compared with expression of ERs in the ovaries of control mice fed ad libitum in granulosa cells (black arrow), ovarian surface epithelium cells (black arrowhead), interstitial cells (black asterisk), and endothelial cells (red asterisk) (b, d, f). There was no immunoreaction in theca cells (b, f; red arrow) and in luteal cells (d; blue arrow) in the ovaries of mice fed ad libitum (b, d, f). Objective magnification: a, b, e, f, x20; c, d, x40

Fig. 2

Immunolocalization and immunoexpression of the AR in the ovaries of mice on CR (a, c, e) and in the ovaries of mice fed ad libitum (b, d, f). One can see a similar expression of the AR in granulosa cells (black arrow) and ovarian surface epithelium cells (black arrowhead) in ovaries of mice on CR (a, c, e) and in ovaries of mice fed ad libitum (b, d, f). Expression of the AR in interstitial cells is shown by black asterisks in ovaries of mice fed ad libitum (b) and in the ovaries of mice on CR (a). Red asterisks indicate expression of AR in endothelial cells in the ovaries of mice fed ad libitum (f) and in the ovaries of mice on CR (a, e). There was no immunoreactions to the AR in theca cells (red arrow) in the ovaries of mice fed ad libitum (b, d). There was very weak expression of the AR in theca cells (red arrow) in the ovaries of mice on CR (a, c). Objective magnification: a, b, e, f, x20; c, d, x40