Physiological and Pathological Androgen Actions in the Ovary

Abstract

Androgens, although traditionally thought to be male sex steroids, play important roles in female reproduction, both in healthy and pathological states. This mini-review focuses on recent advances in our knowledge of the role of androgens in the ovary. Androgen receptor (AR) is expressed in oocytes, granulosa cells, and theca cells, and is temporally regulated during follicular development. Mouse knockout studies have shown that AR expression in granulosa cells is critical for normal follicular development and subsequent ovulation. In addition, androgens are involved in regulating dynamic changes in ovarian steroidogenesis that are critical for normal cycling. Androgen effects on follicle development have been incorporated into clinical practice in women with diminished ovarian reserve, albeit with limited success in available literature. At the other extreme, androgen excess leads to disordered follicle development and anovulatory infertility known as polycystic ovary syndrome (PCOS), with studies suggesting that theca cell AR may mediate many of these negative effects. Finally, both prenatal and postnatal animal models of androgen excess have been developed and are being used to study the pathophysiology of PCOS both within the ovary and with regard to overall metabolic health. Taken together, current scientific consensus is that a careful balance of androgen activity in the ovary is necessary for reproductive health in women.

Fundamental Concepts and Novel Aspects of Polycystic Ovarian Syndrome: Expert Consensus Resolutions

“…The pathophysiological mechanisms by which PCOS negatively impacts on fertility are complex and not completely understood. Undoubtedly, hyperandrogenism, the consequent hyperestrogenemia, IR, and compensatory hyperinsulinemia play an important role acting on both the ovary and the endometrium (16)(17)(18)(19). In addition, there is emerging evidence that proinflammatory cytokines and oxidative stress may directly impact on oocyte quality and may induce endothelial dysfunction, thus contributing to infertility (6,12,13).…”

Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology

“…After 90 days, the rats showed irregular estrous cycles as evidenced by the presence of cornified cells (data not shown) indicating anovulation and ovarian features mimicking PCOS [24]. Administration of androgen to female rats during early postnatal life resulted in polyfollicular anovulatory ovaries during puberty and adulthood [25,26]. The present study evidenced the onset of cysts in the ovaries (Figure 2b), which is corroborated with histopathological observations (Figure 4a) that attest to the utility of the model system employed.…”

What Is the Best Regimen for Ovarian Stimulation of Poor Responders in ART/IVF?

“…Androgen receptors (AR) are expressed in the theca cells, granulosa cells, and ova (25,(32)(33)(34). Expression of AR in follicular cells is critical for normal folliculogenesis and ovulation (25,(32)(33)(34). Therefore, various androgens, mainly testosterone and DHEA, have been clinically tried as cotreatment before and during COS in patients with POR but the success was very limited and equivocal.…”

“…Therefore, various androgens, mainly testosterone and DHEA, have been clinically tried as cotreatment before and during COS in patients with POR but the success was very limited and equivocal. (25,(32)(33)(34). Whereas androgens may augment the early stages of folliculogenesis, they may be detrimental, in supraphysiologic concentrations, on the later stages of folliculogenesis, leading to follicular arrest in the sizes of 2-9 mm, inhibiting the formation of a mature Graaffian follicle, as it is in PCOS patients (33)(34)(35).…”