Gonadotropic control of ovarian follicular growth and development.

Development-related paracrine cues that sensitize follicles to follicle stimulating hormone (FSH) and luteinizing hormone (LH) are crucial to the emergence of a single dominant follicle in each ovulatory menstrual cycle. Sex steroids, insulin-like growth factors and members of the transforming growth factor-beta superfamily are key players in the follicular paracrine system. FSH acts through membrane-associated granulosa cell receptors (FSHR) to stimulate granulosa cell proliferation and differentiation. The most responsive follicle at the beginning of the cycle is the first to produce estrogen and express granulosa cell LHR. Paracrine signalling activated by FSH and LH sustains growth and oestrogen secretion until an ovulation-inducing LH surge is discharged by the pituitary gland. LH then reprograms granulosa cell function, leading to terminal differentiation (luteinization) rupture of the follicle wall, and release of the fertilizable egg. The genes regulated by the LH surge orchestrate profound changes in sex steroid production, metabolism and action which are necessary for ovulation. Preovulatory granulosa cells also increase their ability to metabolise cortisone to cortisol, which may be part of a local anti-inflammatory mechanism to promote rapid healing of the ruptured ovarian surface.