A non-classical role for the mineralocorticoid receptor (MR) in ovarian function (#241)
The role of the mineralocorticoid receptor (MR) in salt and water balance is well established. What remains less clear is its role in non classical tissues. The ovary has been shown to express MR in granulosa cells (GC) and luteal cells; MR blockade in primate ovary inhibits progesterone synthesis. Global MR knockout mice develop sodium wasting and die within the first week of life, making them unsuitable for these studies. We therefore developed a GC-specific MR-null mouse to investigate the hypothesis that the MR plays a central role in ovarian biology, perhaps as a receptor for progesterone, with consequences for ovulation and fertility.
A GC-specific MR-null mouse was generated by crossing AMHR2-cre mice with MR-floxed mice. At 7 weeks of age, ovaries were collected from null mice and littermate controls for histological and gene expression analyses and serum for the measurement of FSH and LH. As expected, the GC-specific MR-null mice were viable. Out of the 4 GC-specific MR null mice examined so far, only 1 had the MR completely deleted from all GC, in all follicles. The remaining 3 either had some follicles where the MR was deleted or no deletion in the GC. Morphologically, the ovaries were similar to controls. Serum FSH levels were not different between control and null mice; however LH levels were significantly reduced in the MR-GC null mice. Since LH initiates ovulation and stimulates progesterone production the implications for ovarian function and fertility are clear. Studies of steroidogenic enzyme expression and apoptosis are in progress.
These studies support a role for the MR in ovarian function. However, the apparent inconsistencies in cre recombination, most likely as a result of variable expression of the cre-recombinase leading to mosaicism in the target tissue, needs to be addressed before definitive conclusions can be drawn.