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 [125I]TGF beta 1 cross-linking, immunolocalization, and immunoprecipitation of T beta RII using receptor-specific antibodies. Granulosa cells of preantral and antral follicles, and interstitial and luteal cells showed strong signal on day 1 at 0900 h; interstitial and luteal staining was maximum. Immunoreactivity in the interstitium fell by day 2 and reappeared on day 4. A sharp reduction of immunostaining occurred after the gonadotropin surge. In hypophysectomized hamsters, FSH induced T beta RII in both granulosa and interstitial cells, but LH was effective only on interstitial cells. Whereas 17 beta-estradiol (17 beta E2) efficiently induced interstitial T beta RII, progesterone severely attenuated E2 induction of receptor protein. Apart from a membrane-associated form of T beta RII, a novel cytosolic form of T beta RII was detected. The cytosolic T beta RII is a glycoprotein with N'-linked oligosaccharides, like its membrane counterpart, possessing 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 with the cytosolic form. Hypophysectomy diminished, whereas FSH, LH, and 17 beta E2 increased both forms of T beta RII; however, LH induction of the cytosolic form was greater than that by FSH. Progesterone prevented T beta RII protein integration to the membrane, but testosterone and dihydrotestosterone were also effective in T beta RII induction in the membrane. A high E2/progesterone ratio was an important determinant in T beta RII induction in the cell membrane. These results provide the first direct evidence for the presence of a functional T beta RII in the ovary. The receptor is a serine/threonine kinase and exists as distinct cytosolic and membrane forms that show a unique relationship during the estrous cycle. The induction of ovarian T beta RII is critically and temporally influenced by gonadotropins and ovarian steroid hormones.
Roy
S K
SK
Leland J. And Dorothy H. Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha 68198-4515, USA.
Kole
A R
AR
D000818:Animals; D006224:Cricetinae; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006062:Gonadotropins / Q000502:physiology; D007016:Hypophysectomy; D015151:Immunoblotting; D010053:Ovary / Q000737:chemistry*; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases