Transforming Growth Factor-α and -β Differentially Regulate Growth and Steroidogenesis of Bovine Thecal Cells during Antral Follicle Development

The actions and interactions of transforming growth factor-a (TGFa) and TGF/3 on growth and differentia- tion of bovine thecal cells were investigated. Bovine thecal interna cells were isolated from small ( 10 mm) antral follicles and cultured in the presence or absence of TGFa and/or TGF/3. Both ( 3 H)thymidine incorporation and changes in cell number (i.e. DNA levels) were evaluated to determine effects on thecal cell growth. Short term treatment of cells with TGFa (18-24 h) stimulated thymidine incorporation, and longer term treatments (4 days) increased cell number. TGFjS suppressed thymidine incorporation below that observed in untreated cultures, but had no effect on cell number. When combined with TGFa, TGF/3 suppressed the ability of TGFa to stimulate thymidine incorporation and in- crease cell number. The response to these growth factors was similar for cells isolated from the different stages of antral follicle development. The effects of TGFa and TGF/3 on thecal cell differentiation were evaluated by quantitating changes in androstenedione and progesterone accumulation in cultures treated with TGFs in the absence (basal) or presence of hCG, estradiol (E 2), or a combination of hCG and E2. E2 and hCG were included in this study because previous research has dem- onstrated that these hormones alter thecal cell steroidogenesis. Treatment with TGFa resulted in a suppression of basal and hormonally stimulated accumulation of androstenedione during days 0-3 of culture, whereas TGF/3 did not significantly alter androstenedione accumulation. TGFa also suppressed proges- terone accumulation during days 0-3 of culture in the absence or presence of hormones. In contrast, TGF/3 stimulated accu- mulation of progesterone in cultures that did not contain E2, which suppressed progesterone during this period. Therefore, during days 0-3 of culture, TGFa appears to have suppressive effects on androstenedione and progesterone production, whereas TGF/3 can stimulate progesterone production in the absence of E2. During days 3-6 of culture, thecal cell differentia- tion changes, and the capacity to produce androstenedione dra- matically declines, while the capacity to produce progesterone increases. During this period, either TGFa or TGF/3 slightly increased basal progesterone accumulation and partially sup- pressed the ability of hCG to stimulate progesterone. The effects of TGFs on thecal cell steroidogenesis were similar with cells isolated from the different stages of antral follicle development. Results from these studies provide evidence that TGFa and TGFjS can modulate thecal cell growth and differentiation (i.e. steroidogenesis). The inverse actions of these growth factors on thecal cell proliferation provide an efficient mechanism by which the growth of follicles may be regulated. The effects of TGFa and TGF/3 on steroidogenesis may be associated with these growth effects. The ability of TGFa to stimulate cell growth may decrease cell differentiation, which correlates with the generally suppressive effects of TGFa on steroidogenesis ob- served. In contrast, TGFjS inhibits growth, which may promote cell differentiation, and this correlates with the stimulatory effects of TGF/3 on steroidogenesis observed. The ability of thecal cells to produce and respond to these growth factors provides evidence that TGFa and TGF/3 may act as important autocrine factors to influence the growth and differentiation of thecal cells during follicle development. (Endocrinology 129: 2041-2048,1991)