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

ANDREW J ROBERTS; MICHAEL K SKINNER

doi:10.1210/endo-129-4-2041

The actions and interactions of transforming growth factor-α (TGFα) and TGFβ on growth and differentiation of bovine thecal cells were investigated. Bovine thecal interna cells were isolated from small (<5 mm), medium (5-10 mm), and large (>10 mm) antral follicles and cultured in the presence or absence of TGFα and/or TGFβ. Both [3H]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 TGFβ (18-24 h) stimulated thymidine incorporation, and longer term treatments (4 days) increased cell number. TGFβ suppressed thymidine incorporation below that observed in untreated cultures, but had no effect on cell number. When combined with TGFα, TGFβ) suppressed the ability of TGFα to stimulate thymidine incorporation and increase cell number. The response to these growth factors was similar for cells isolated from the different stages of antral follicle development. The effects of TGFα and TGFβ 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 (E2), or a combination of hCG and E2. E2 and hCG were included in this study because previous research has demonstrated that these hormones alter thecal cell steroidogenesis. Treatment with TGFα resulted in a suppression of basal and hormonelly stimulated accumulation of androstenedione during days 0-3 of culture, whereas TGFβ did not significantly alter androstenedione accumulation. TGFα also suppressed progesterone accumulation during days 0-3 of culture in the absence or presence of hormones. In contrast, TGFβ stimulated accumulation of progesterone in cultures that did not contain E2, which suppressed progesterone during this period. Therefore, during days 0-3 of culture, TGFα appears to have suppressive effects on androstenedione and progesterone production, whereas TGFβ can stimulate progesterone production in the absence of E2. During days 3-6 of culture, thecal cell differentiation changes, and the capacity to produce androstenedione dramatically declines, while the capacity to produce progesterone increases. During this period, either TGFα or TGFβ slightly increased basal progesterone accumulation and partially suppressed 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 TGFα and TGFβ 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 TGFα and TGFβ on steroidogenesis may be associated with these growth effects. The ability of TGFα to stimulate cell growth may decrease cell differentiation, which correlates with the generally suppressive effects of TGFα on steroidogenesis observed. In contrast, TGFβ inhibits growth, which may promote cell differentiation, and this correlates with the stimulatory effects of TGFα on steroidogenesis observed. The ability of thecal cells to produce and respond to these growth factors provides evidence that TGFα and TGFβ may act as important autocrine factors to influence the growth and differentiation of thecal cells during follicle development.

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

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