Effect of TNF-alpha on LH and IGF-I modulated chicken granulosa cell proliferation and progesterone production during follicular development.

This study demonstrates the effects of recombinant human tumour necrosis factor a (rhTNF-alpha) and conditioned medium of the HD11-transformed chicken macrophage cell line on cultured chicken granulosa cells. Effects were studied on basal, IGF-I- and LH-stimulated progesterone production and cell proliferation. Recombinant human TNF-alpha stimulated basal progesterone production in a dose-dependent manner in the granulosa cells of the largest follicle but had no effect on cells from the third largest follicle. TNF-alpha stimulated and sometimes inhibited progesterone production stimulated by IGF-I and LH alone or in combination depending on the size of the follicle and the concentration of LH or IGF-I applied. However, the inhibitory effect of TNF-alpha was significantly more pronounced in cells from the third largest follicle when high concentrations of IGF-I, LH or a combination of both were applied. TNF-alpha had no effect on basal cell proliferation in both the largest and the third largest follicles, but regulated responses to IGF-I and a combination IGF-I and LH in the cells of the third largest follicle but not those of the largest follicle. The data indicate that the normal hierarchy of follicles is maintained in the chicken ovary through the regulation of the activity of IGF-I and its interaction with LH. Conditioned medium of LPS-activated HD11 macrophages mimicked the effects of TNF-alpha and its interaction with IGF-I and LH on progesterone production and cell proliferation. The observation that the HD11-conditioned medium contained TNF-alpha indicates that TNF-alpha produced by macrophages found in chicken follicles modulates granulosa cell growth and differentiation.