The role of androgen hormones in early follicular development

Abstract

Background. Although chronic hyperandrogenism, a typical feature of polycystic ovary syndrome, is often associated with disturbed reproductive performance, androgens have been shown to promote ovarian follicle growth in shorter exposures. Here, we review the main effects of androgens on the regulation of early folliculogenesis and the potential of their application in improving follicular in vitro growth. Review. Androgens may affect folliculogenesis directly via androgen receptors (ARs) or indirectly through aromatization to estrogen. ARs are highly expressed in the granulosa and theca cells of early stage follicles and slightly expressed in mature follicles. Short-term androgen exposure augments FSH receptor expression in the granulosa cells of developing follicles and enhances the FSH-induced cAMP formation necessary for the transcription of genes involved in the control of follicular cell proliferation and differentiation. AR activation also increases insulin-like growth factor (IGF-1) and its receptor gene expression in the granulosa and theca cells of growing follicles and in the oocytes of primordial follicles, thus facilitating IGF-1 actions in both follicular recruitment and subsequent development. Conclusion. During the early and intermediate stages of follicular maturation, locally produced androgens facilitate the transition of follicles from the dormant to the growing pool as well as their further development.

Figure 1

Schematic view of the production of androgen hormones by ovarian follicular cells according to the two-cells-two-hormones model. In the theca cells, the androgens (androstenedione and testosterone) are produced in response to the luteinizing hormone (LH) stimulus. After diffusing towards the granulosa cells, the androgens are converted to estrogens (estradiol and estrone) by the enzyme aromatase under the action of the follicle stimulating hormone (FSH). P450scc, enzyme responsible for the cleavage of the lateral chain of cholesterol; 3β-HSD, 3β-hydroxysteroid dehydrogenase; 17β-HSD, 17β-hydroxysteroid dehydrogenase.

Figure 2

Schematic presentation of the action of androgen hormones on early follicular development. The androgens produced by the growing follicles can promote the transition from (1) primordial to primary follicles and (2) from primary to secondary follicles through the amplification of the actions of the IGF-1 system and can also amplify the actions of follicle stimulating hormone (FSH) on the promotion of the subsequent growth of (3) preantral and (4) antral follicles.