FSH induction of functional LH receptors in granulosa cells cultured in a chemically defined medium

Abstract

THE rat ovarian granulosa cell is an excellent model for studying the mechanisms and control of hormone-dependent cell differentiation. During graafian follicle development, the granulosa cells sequentially develop specific membrane receptor sites for follicle-stimulating hormone (FSH)^1,2 and luteinising hormone (LH)³. In vivo studies on the mechanism of granulosa cell differentiation have established that FSH induces the appearance of the LH receptor sites in the granulosa cell^4,5. The FSH-induced increase in LH receptors is essential for preparing the graafian follicle for the pre-ovulatory surge of LH which initiates ovulation and subsequent luteinisation of the granulosa cells. Studies of cultured granulosa cells have led to the suggestion that the FSH induction of LH receptors is not a direct process but requires an interaction between the granulosa cell and other ovarian cell types, a concept consistent with the known importance of cell–cell interaction in cell differentiation⁶. This hypothesis stemmed from the observation that LH receptors can be induced by FSH in granulosa cells in vivo and in organ cultures of intact ovarian follicles, but not in isolated granulosa cells cultured as monolayers in medium containing serum^7,8. We show here that the inability of previous workers^7,8 to induce LH receptors in isolated granulosa cells may have been due to the use of serum in their tissue culture medium. We demonstrate that specific, high-affinity LH/hCG receptors can be induced by FSH in isolated granulosa cells cultured in a chemically defined medium, but not in isolated granulosa cells cultured with serum. In addition, we show that these receptors are capable of mediating important steroidogenic responses.