Abstract
The steroidogenic pathway within the ovary gives rise to progestins, androgens and oestrogens, all of which act via specific nuclear receptors to regulate reproductive function and maintain fertility. The role of progestins in follicular growth and development is limited, its action confined largely to ovulation, although direct effects on granulosa cell function have been reported. Consistent with these findings, progesterone receptor knockout mice are infertile because they cannot ovulate. Androgens have been shown to promote early follicular growth, but also to impede follicular development by stimulating atresia and apoptosis. The inability of androgens to transduce a signal in mice lacking androgen receptors culminates in reduced fertility. Oestrogens are known to exert effects on granulosa cell growth and differentiation in association with gonadotrophins. Studies with oestrogen receptor knockouts and oestrogen depleted mice have shown us that oestrogen is essential for folliculogenesis beyond the antral stage and is necessary to maintain the female phenotype of ovarian somatic cells. In summary, the action of steroids within the ovary is based on the developmental status of the follicle. In the absence of any single sex steroid, ovarian function and subsequently fertility, are compromised.
Highlights
Follicular development begins during foetal life with the transformation of primordial germ cells into oocytes and their enclosure in structures called follicles
Primordial follicles give rise to primary follicles which transform into preantral antral follicles and preovulatory, Graafian follicles, in a co-ordinated series of transitions regulated by hormones and local intraovarian factors
Produced de novo from cholesterol, progestins, androgens and oestrogens are synthesised by the ovary in a sequential manner, with each serving as substrate for the subsequent steroid in the pathway
Summary
Follicular development begins during foetal life with the transformation of primordial germ cells into oocytes and their enclosure in structures called follicles. Apart from effects on growth, androgens have been shown to enhance the follicle stimulating hormone (FSH)-mediated differentiation of granulosa cells, as indicated by an increase in progesterone and oestradiol production [7476] and to play roles in oocyte maturation. Despite similarities with the sex reversed cells reported in ArKO or ER double knockout mouse ovaries, these transdifferentiated follicular cells did not express Sox 9 They established a role for FSH in the development of these transdifferentiated oocyte depleted follicles. Otsuka and colleagues [167] recently reported that oocytes mediate oestrogen's enhancement of FSH action on P450 aromatase, FSH and LH receptor and inhibin/activin subunit mRNA expression and cAMP production by granulosa cells in vitro [167]
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