DEVELOPMENTAL REGULATION OF ANDROGEN RECEPTOR IN RAT OVARY

Androgen receptor (AR) distribution and developmental regulation in th e rat ovary were examined by semiquantitative immunohistochemistry. Ov arian AR mRNA levels were also determined by Northern analysis of tota l RNA and compared with the levels of cytochrome P450aromatase (P450ar om), an established marker of preovulatory follicular maturity. Hypoph ysectomized immature female rats were treated with recombinant human ( rh)-FSH and/or rh-LH, or human menopausal. gonadotrophin (HMG). AR was predominately located in granulosa cells. There was no indication of specific AR immunoreactivity in thecal cells, but scattered stromal ce lls did stain positively, In control and LH-treated ovaries, only smal l preantral/early antral follicles were present. Granulosa cells in th ese follicles showed intense AR immunostaining. Treatment with FSH, FS H and LH or HMG stimulated varying degrees of preovulatory follicular development. In these follicles, the intensity of AR immunostaining pr ogressively declined as follicular development progressed. In intact i mmature rats treated with FSH, the abundance of ovarian AR mRNA was si gnificantly decreased to 35% of the control value while combined treat ment of FSH and LH resulted in further down-regulation of AR mRNA expr ession to 17% of the control value. A decrease in the abundance of AR mRNA was accompanied by a simultaneous increase in the abundance of P4 50arom mRNA. Similar results were obtained in hypophysectomized immatu re rats treated with FSH and LH, suggesting an inverse relationship be tween AR mRNA expression and granulosa cell maturity. These results su ggest that (1) the AR is most abundant in the granulosa cells of rat o varies and (2) the expression of AR and its mRNA are developmentally r egulated, being down-regulated during FSH-stimulated preovulatory foll icular development.