The role of estrogen in folliculogenesis.

Gonadotrophins are fundamental to the mechanisms regulating follicle status and development. Follicles in the ovary are either quiescent or committed to one of two pathways: growth or atresia. The requirement for gonadotrophins by the follicles varies with development: committed follicles grow independently of gonadotrophins (primarily FSH) until the late preantral stage when antrum formation is contingent upon FSH. The involvement of estrogen in regulating gonadotrophin secretion is well documented and while evidence for a local regulatory role of estrogen in the ovary mounts, an obligatory role for estrogen in the folliculogenic process has not been established. The availability of a wide range of gene-disrupted mice termed 'knockouts', is providing information relevant to the study of folliculogenesis. Mice deficient in either estrogen or estrogen receptors, are infertile primarily due to either a block in folliculogenesis prior to antrum formation or as a consequence of failing to ovulate. Blocking estrogen stimulated, post-receptor molecules such as cyclin D2, severely retards granulosa cell proliferation and leads to infertility, although the contribution of estrogen in this model is not so clear given that FSH also stimulates cyclin D2. Similar problems dissociating the roles of FSH and estrogen are evident with the FSH deficient animal models. Nevertheless, estrogen is clearly an important and probably obligatory regulator of folliculogenesis, especially in the post antral stage. The exact points in the folliculogenic process where estrogen exerts its principal effects remains to be elucidated.