Intragonadal regulation of follicular maturation

Although there are interspecies of variations in the process of follicular development, a generalized summary is presented that encompasses theories of follicular maturation from laboratory and domestic animals, nonhuman primates, and women. As there are many new substances whose actions within the follicle are unknown, it is difficult to ascribe definitive roles to these proteins in follicular development and ovulation. However, where possible, these substances are included in the summary. During early follicular development, FSH binds to granulosa cells of primary follicles to stimulate production of estradiol by the induction or enhancement of aromatase synthetase (37, 336, 337). Estradiol, in turn, induces proliferation of granulosa cells (338-344) and increases the sensitivity of the follicle to further gonadotropin stimulation (12, 339, 345-349). Estradiol can synergize with gonadotropins to increase ovarian weight, enhance proliferation of granulosa cells, and promote growth of preantral follicles and antrum formation (345, 347, 350-352). In addition, estradiol enhanced the responsiveness of granulosa cells to FSH and LH by increasing synthesis of progesterone (353, 354). The generalized enhancement of gonadotropin action by estradiol is partially mediated by FSH-induced accumulation of cAMP. However, as synthesis of estradiol increases, this steroid directly stimulated follicular growth, since estrogens have long been known to stimulate growth of ovarian cells and exert a direct antiatretic effect (355, 356). However, the exact mechanism involved in follicular growth achieving preovulatory status rather than undergoing atresia remains uncertain. Estradiol not only enhances gonadotropin stimulation of LH and FSH receptors in granulosa cells (357, 348) but is required for FSH induction of FSH receptors (359, 360). Estradiol alone can increase numbers of its own receptor in granulosa cells (350) as well as increase its own production by stimulating aromatase activity (361). Estradiol secreted by the dominant follicle has a positive feedback effect on the hypothalamus and pituitary, enhancing gonadotropin secretion and ensuring the preovulatory gonadotropin surges (362). The increased gonadotropins can further increase the production of estradiol which, in turn, enhances its own production. Therefore, estradiol is included in two positive feedback loops (one at the pituitary and one at the ovary) to maintain the dominant follicle and ensure ovulation. Progesterone and androgens also have intrafollicular effects on follicular growth and steroidogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)