ANDROGEN RECEPTOR GENE-EXPRESSION IN THE PRIMATE OVARY - CELLULAR-LOCALIZATION, REGULATION, AND FUNCTIONAL CORRELATIONS

Excess androgens are associated with a characteristic polyfollicular o varian morphology; however, it is not known to what extent this proble m is due to direct androgen action on follicular development us. inter ference with gonadotropin release at the level of the pituitary or hyp othalamus. To elucidate potential androgen effects on the ovary, we in vestigated the cellular localization of androgen receptor (AR) messeng er ribonucleic acid (mRNA) in rhesus monkey using in situ hybridizatio n. To investigate the regulation of ovarian AR gene expression, we com pared the relative abundance of AR transcripts in monkeys during folli cular and luteal phases of the menstrual cycle and in monkeys treated with testosterone. To assess potential functional consequences of AR e xpression in the primate ovary, we compared AR mRNA levels with indexe s of follicular cell proliferation and apoptosis in serial sections fr om individual follicles. AR mRNA expression was most abundant in granu losa cells of healthy preantral and antral follicles in the primate ov ary. Theca interns and stromal cells also expressed AR mRNA, but to a lesser degree than granulosa cells. No significant cycle stage effects were noted in AR mRNA levels; however, larger numbers of animals woul d be necessary to definitively establish a cycle stage effect. AR mRNA level was significantly increased in granulosa cells and was decrease d in theca interna and stromal cells of testosterone-treated monkeys. Importantly, granulosa cell AR mRNA abundance was positively correlate d with expression of the proliferation-specific antigen Ki-67 (r = 0.9 1; P < 0.001) and negatively correlated with granulosa cell apoptosis (r = -0.64; P < 0.001). In summary, these data show that primate ovary AR gene expression is most abundant in granulosa cells of healthy gro wing follicles, where its expression is up-regulated by testosterone. The positive correlation between granulosa AR gene expression and cell proliferation and negative correlation with programmed cell death sug gests that androgens stimulate early primate follicle development.