ENHANCED OVARIAN INHIBIN SUBUNIT GENE-EXPRESSION IN AGING RATS IS DUETO CHRONIC ANOVULATION

The persistent-estrous (PE) state in aging rats, characterized by a la ck of ovulation and absence of estrous cycles, is associated with enha nced inhibin alpha and beta(A) subunit mRNA expression in the ovaries. It has been shown that the PE state can be interrupted by successive treatments with a progesterone implant (P-implant) and that estrous cy cles can be transiently restored after implant removal. The present st udy examined whether restoration of estrous cycles in PE rats could re verse the altered ovarian inhibin alpha and beta(A), subunit gene expr ession. PE rats were treated with subcutaneous P-implants for 6 wk. Af ter implant removal, the return of estrous cyclicity was confirmed by characteristic cyclic changes in vaginal cytology. Ovaries collected f rom the P-implant-treated animals at 1 100 h on diestrus Day 2 or proe strus showed significantly decreased levels of both inhibin alpha and beta(A) subunit mRNAs compared to those of PE controls and young cycli c females. In situ hybridization revealed that the decreased inhibin a lpha subunit mRNA after P-implants was due to decreased gene expressio n in the granulosa cells of large preovulatory follicles and to a comp lete absence of gene expression in large, cystic follicles devoid of g ranulosa cells and oocytes. In addition, inhibin alpha subunit mRNA wa s expressed in the newly developed follicles after implant removal. Th e beta(A), subunit mRNA was detected only in maturing follicles, not i n newly developing follicles or in the large cystic follicles. The pat terns of ovarian inhibin alpha and beta(A) subunit gene expression mim icked those of cyclic animals. These data indicate that loss of estrou s cycles in aging rats results in an overexpression of inhibin alpha a nd beta(A), mRNAs in large and anovulatory follicles and that reinstat ement of ovarian cycles in aged rats restores inhibin gene expression to normal levels.