Abstract
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-α) was overexpressed in LH-treated preovulatory GCs, as determined by a microarray analysis. In this study, we evaluated the expression of IFN-α 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-α production and cell differentiation were determined. Stimulation of rat primary GCs with LH or hCG increased expression of IFN-α. 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-α expression in preovulatory GCs. Furthermore, treatment with anti-rat IFN-α 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-α expression in preovulatory GCs via a PI3-K/ERK signaling pathway and that interferon-α production may be involved in the LH-induced differentiation of preovulatory GCs in rats.
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