TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR-TYPE-II EXPRESSION IN THE HAMSTER OVARY - CELLULAR SITE(S), BIOCHEMICAL-PROPERTIES, AND HORMONAL-REGULATION

The hormonal regulation of transforming growth factor-beta (TGF beta) receptor type II (T beta RII) protein expression in the hamster ovary was evaluated by [I-125]TGF beta 1 cross-linking, immunolocalization, and immunoprecipitation of T beta RII using receptor-specific antibodi es. Granulosa cells of preantral and antral follicles, and interstitia l and luteal cells showed strong signal on day 1 at 0900 h; interstiti al and luteal staining was maximum. Immunoreactivity in the interstiti um fell by day 2 and reappeared on day 4. A sharp reduction of immunos taining occurred after the gonadotropin surge. In hypophysectomized ha msters, FSH induced T beta RII in both granulosa and interstitial cell s, but LH was effective only on interstitial cells. Whereas 17 beta-es tradiol (17 beta E(2)) efficiently induced interstitial T beta RII, pr ogesterone severely attenuated E(2) induction of receptor protein. Apa rt from a membrane-associated form of T beta RII, a novel cytosolic fo rm of T beta RII was detected. The cytosolic T beta RII is a glycoprot ein with N'-linked oligosaccharides, like its membrane counterpart, po ssessing serine-threonine kinase activity that is TGF beta sensitive. The membrane-associated T beta RII disappeared on day 2 of the cycle, but reappeared by day 4 in the morning. A good correlation was found w ith the cytosolic form. Hypophysectomy diminished, whereas FSH, LH, an d 17 beta E(2) increased both forms of T beta RII; however, LH inducti on of the cytosolic form was greater than that by FSH. Progesterone pr evented T beta RII protein integration to the membrane, but testostero ne and dihydrotestosterone were also effective in T beta RII induction in the membrane. A high E(2)/progesterone ratio was an important dete rminant in T beta RII induction in the cell membrane. These results pr ovide the first direct evidence for the presence of a functional T bet a RII in the ovary. The receptor is a serine/threonine kinase and exis ts as distinct cytosolic and membrane forms that show a unique relatio nship during the estrous cycle. The induction of ovarian T beta RII is critically and temporally influenced by gonadotropins and ovarian ste roid hormones.