OVARIAN REGULATION OF PITUITARY INHIBIN SUBUNIT AND ACTIVIN RECEPTOR-TYPE-II GENE-EXPRESSION - EVIDENCE FOR A NONSTEROIDAL INHIBITORY SUBSTANCE

Gonadotropin subunit gene expression is regulated by gonadal, hypothal amic, and locally derived hormones. In particular, activin rapidly (wi thin hours) acts at the gonadotrope to selectively increase the expres sion of FSH beta messenger RNA (mRNA). A family of activin receptors ( ActRI, ActRII, and ActRIIB) has been identified, which is expressed in the pituitary as well as numerous other tissues in which activin is t hought to act. As alterations in activin sensitivity could modulate ac tivin action and, thereby, FSH beta mRNA, the purpose of this study wa s to determine whether ovariectomy (OVX), which results in rapid (<2 h ) increases in FSH beta, is associated with changes in ActRII gene exp ression. Adult female rats were ovariectomized, and some animals also received a GnRH antagonist from the time of OVX. Animals were killed b etween 2 h and 7 days later, and ActRII mRNA levels were measured by a quantitative reverse transcriptase polymerase chain reaction assay. A lthough levels were unchanged at 2 h, ActRII mRNA levels increased 5- to 6-fold by 8 h and remained increased through 7 days after OVX. Thes e changes were not altered by GnRH blockade. To determine whether ActR II was regulated by gonadal steroids, female rats were ovariectomized, and some animals were replaced with estradiol and progesterone (Silas tic implants) for 2 days. Again, ActRII mRNA levels increased signific antly after OVX, and gonadal steroid replacement had no effect. Finall y, to investigate whether pituitary ActRII mRNAs are regulated by circ ulating inhibin, intact female rats were treated with an inhibin antis erum or nonimmune sheep serum as a control and killed 12 h later. Desp ite its action to increase FSH beta mRNA and FSH secretion, selective removal of inhibin did not alter ActRII mRNA levels. Based on these re sults we conclude the following. 1) Pituitary ActRII mRNAs increase ra pidly after OVX, although increases in FSH beta precede changes in Act RII. These data suggest that changes in activin sensitivity may be a f actor involved in the regulation of FSH beta. 2) An ovarian factor, ot her than inhibin, estradiol, and progesterone, acting independently of GnRH maintains an inhibitory tone on pituitary ActRII gene expression in adult rats.