CELL-TYPE-SPECIFIC LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA-2 AND TRANSFORMING GROWTH FACTOR-BETA-1 IN THE HAMSTER OVARY - DIFFERENTIAL REGULATION BY FOLLICLE-STIMULATING-HORMONE AND LUTEINIZING-HORMONE

Cell-type-specific localization and gonadotropin regulation of transforming growth factor-beta-1 (TGF-beta-1) and transforming growth factor-beta-2 (TGF-beta-2) in the hamster ovary were evaluated immunohistochemically under three conditions: (1) during the estrous cycle (Day 1 = estrus; Day 4 = proestrus); (2) after the blockade of periovulatory gonadotropin surges by phenobarbital, and (3) after FSH and/or LH treatment of long-term hypophysectomized hamsters. Ovarian TGF-beta-1 activity was primarily localized in theca and interstitial cells. The activity increased moderately but significantly after the preovulatory LH surge and reached a peak at 0900 h, Day 2 h; oocytes showed considerable activity. TGF-beta-1 immunoreactivity subsequently fell to low levels in thecainterstitial cells through 0900 h, Day 4. Significant TGF-beta-2 immunoreactivity appeared after the surge, mainly in the granulosa cells of both preantral and antral follicles; a few interstitial cells surrounding preantral follicles showed discrete staining. TGF-beta-2 immunoreactivity in granulosa cells and in interstitial cells next to preantral follicles reached a peak at 0900 h, Day 1, and persisted up to 0900 h, Day 2; oocytes showed no staining. Phenobarbital treatment blocked the appearance of TGF-beta-1 and TGF-beta-2 immunoreactivities at 1600 h, Day 4; however, a rebound in immunoreactivities was observed with the onset of the surge after a 1-day delay. Replacement of LH to long-term hypophysectomized hamsters resulted in a marked increase in TGF-beta-1 immunoreactivity in the interstitial cells, but FSH, although it induced follicular development, did not influence ovarian TGF-beta-1 activity. Treatment with FSH, however, induced a massive increase in TGF-beta-2 immunoreactivity in the granulosa cells of newly developed antral and preantral follicles but not in the interstitial cells; LH, on the other hand, had no significant effect on TGF-beta-2 activity. Treatment with FSH and LH combined resulted in a dramatic increase in TGF-beta-2 immunoreactivity in granulosa and interstitial cells and in TGF-beta-1 in theca and interstitial cells comparable to their peak activity in intact animals. Western analyses substantiated the presence of TGF-beta-1 and TGF-beta-2 in the hamster ovary and the specificity of immunolocalization. These studies, therefore, provide critical evidence that TGF-beta-1 and TGF-beta-2 in the hamster ovary are expressed in specific cell types and that their expression is differentially regulated by LH and FSH, respectively.