Modulation of ovarian structure and abdominal obesity in curcumin- and flutamide-treated aging FSH-R haploinsufficient mice.

We have previously shown that follicle-stimulating hormone receptor haploinsufficient mice undergo early reproductive senescence with alterations in ovarian structures. The objective of this study was to treat aging (7-8 months) +/- follicle-stimulating hormone receptor mice that are destined for reproductive failure with 2 selected antiandrogens, curcumin and flutamide, to counteract deleterious effects of mild hyperandrogenemia on the ovary and metabolism. Both compounds significantly downregulated the expression of ovarian androgen receptor protein and simultaneously reduced cyclooxygenase 2 protein in the ovary. Immunolocalization of bone morphogenetic protein-15 in the ovary was enhanced considerably by curcumin and partially by flutamide in treated mice. Improved structural changes were evident in zona pellucida of curcumin-treated ovaries. Flutamide reduced p450c-17 (cyp-17 protein) enzyme expression in thecal/interstitial cells, whereas increased expression of 3beta-hydroxysteroid dehydrogenase in thecal cells and granulosa-lutein cells of big follicles was apparent in curcumin-treated ovaries. Reduction in abdominal adiposity was greater in flutamide-treated mice. Taken together, our study allows the following conclusions: changes in ovarian histology and oocyte components as well as adipose tissue indicate the potential for reversing ovarian decline and metabolism because of mild hyperandrogenemia that occurs with aging in follicle-stimulating hormone receptor haploinsufficienct mice.