Modulation of hen granulosa cell steroidogenesis and plasminogen activator activity hy transforming growth factor...

Studies were conducted with chicken granulosa cells to evaluate the relative efficacy of human recombinant transforming growth factor alpha (TGF alpha) versus murine epidermal growth factor (EGF) to affect cyclic adenosine monophosphate (cAMP) accumulation and progesterone production stimulated by luteinizing hormone (LH) or steroid output induced by a cAMP analogue, and to modulate plasminogen activator (PA) activity. Increasing concentrations of EGF (33-328 nM) and TGF alpha (0.04-18 nM) were found to inhibit cAMP formation stimulated by LH in a dose-dependent manner, with calculated half-maximal inhibitory doses (ID50's) of 97.1 and 0.27 nM, respectively. Similarly, a 470-fold difference in the ability of TGF alpha (ID50 = 0.13 nM) versus EGF (ID50 = 61.3 nM) to half-maximally suppress LH-induced progesterone production was observed in the same cells. Progesterone production stimulated by a cAMP analogue (8-bromo-cAMP, 1 mM) was also attenuated by EGF (ID50 = 75.9 nM) and TGF alpha (ID50 = 0.08 nM), suggesting a post-cAMP site of inhibition by these growth factors on steroidogenesis. Finally, a 260-fold to 330-fold difference in the efficacy of TGF alpha versus EGF to half-maximally stimulate cell-associated and secreted PA activity was observed. From these data, we propose that TGF alpha may serve an important role in regulating follicular growth and maturation in the domestic hen via its ability to affect granulosa cell steroidogenesis and plasminogen activator activity.