Transforming growth factor-beta regulates the expression of luteinizing hormone receptors in ovarian granulosa cells

In cultured granulosa cells, addition of 1 to 50 ng follicle-stimulating hormone induced a 350-fold rise in luteinizing hormone receptors, while larger amounts of gonadotropin up to 200 ng reduced these receptors to approximately 50% of peak levels. Transforming growth factor-beta (16 pM) enhanced the stimulatory actions of low levels of gonadotropin (2.5-10 ng) by 2 to 3-fold, and inhibited the induction of luteinizing hormone receptors by higher levels of follicle-stimulating hormone (greater than or equal to 50 ng) by 30-50%. The actions of the growth factor were concentration-dependent over the range from 0.8 to 16 pM and included a similar biphasic effect upon gonadotropin-induced cAMP production. Modulation of cAMP formation and luteinizing hormone receptor expression by transforming growth factor-beta could influence the ability of the granulosa cell to respond to luteinizing hormone during ovarian follicular maturation and ovulation.