Interferon-α is involved in the luteinizing hormone-induced differentiation of rat preovulatory granulosa cells

A surge in luteinizing hormone (LH) triggers physiological changes within the ovarian follicles, including reprogramming to induce terminal differentiation of the granulosa cells (GCs). Cytokines are members of a large regulatory network that resides in the ovaries and are involved in the regulation of steroidogenesis and gamete production. Recently we found that interferon-alpha (IFN-) was overexpressed in LH-treated preovulatory GCs, as determined by a microarray analysis. In this study, we evaluated the expression of IFN- and its role in the differentiation of rat preovulatory GCs. Rat GCs were treated with LH in vitro or human chorionic gonadotropin (hCG) in vivo, both of which are well-known inducers of differentiation, and IFN- production and cell differentiation were determined. Stimulation of rat primary GCs with LH or hCG increased expression of IFN-. LH treatment led to increased phosphorylation of PI3-K and extracellular signal-regulated kinase (ERK), and specific inhibitors for PI3-K and ERK suppressed the LH-induced IFN- expression in preovulatory GCs. Furthermore, treatment with anti-rat IFN- blocking antibody delayed the LH-induced differentiation of GCs and suppressed the expression of ovulation-related genes, including progesterone receptor (PR) and steroidogenic acute regulatory protein (StAR). These results indicate that LH induces IFN- expression in preovulatory GCs via a PI3-K/ERK signaling pathway and that interferon- production may be involved in the LH-induced differentiation of preovulatory GCs in rats.