Involvement of androgens in ovarian health and disease

Abstract

In women, ovary and adrenal gland produce androgens. Androgens are essential drivers of the primordial to antral follicle development, prior to serving as substrate for estrogen production in the later stages of folliculogenesis. Androgens play a crucial role in the follicular-stromal intertalk by fine tuning the extracellular matrix and vessel content of the ovarian stroma. Local auto-and paracrine factors regulate androgen synthesis in the pre-antral follicle. Androgen excess is a hallmark of polycystic ovary syndrome and is a key contributor in the exaggerated antral follicle formation, stromal hyperplasia and hypervascularity. Hyperandrogenaemia overrides the follicular-stromal dialog, resulting in follicular arrest and disturbed ovulation. On the other hand, androgen deficiency is likely to have a negative impact on fertility as well, and further research is needed to examine the benefits of androgen-replacement therapy in subfertility.

An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence

“…In PCOS, the balance between androgens, anti-Müllerian hormone (AMH), and FSH is disrupted leading to follicular arrest [7]. Abundant LH drives the theca cells to produce androgens, but FSH concentrations and conversion of androgens to estradiol are insufficient, resulting in failure to select a dominant follicle, thus chronic anovulation [8]. AMH, secreted by granulosa cells, plays a major role in governing this balance because it inhibits transition from primordial to primary follicles.…”

Androgen actions in the ovary: balance is key

“…Another area that has received little attention to date is membrane-initiated AR signaling, its interaction with other steroids and growth factors and specific aspects of ovarian physiology regulated by AR signaling. For example, it is hypothesized (Yang et al 2010, Lebbe & Woodruff 2013 that the AR-induced PI3K/AKT pathway through modulation of FOXO3 and GDF9 may be involved in primordial follicle recruitment. However, further studies are needed to establish this fact.…”

“…Moreover, other than the recent report that androgens may regulate FSHR levels in a transcriptionindependent fashion (Sen et al 2014), nothing is known about the non-genomic effects of androgens and the hormone's underlying mechanism in the ovary. Many over the years have also proposed the idea that androgens may regulate AMH expression and/or levels (Lebbe & Woodruff 2013). This idea comes from correlation studies showing a positive relationship between androgens and AMH levels in follicular fluid.…”

“…While androgen excess enhances follicular development and dysfunctional formation of antral follicles leading to polycystic ovary syndrome (PCOS), low androgen levels may be associated with abnormalities of follicular growth, low functional ovarian reserve (LFOR) and primary ovarian insufficiency (POI), thereby negatively impacting female fertility. Many studies (Kimura et al 2007, Walters et al 2008, Sen & Hammes 2011, Lebbe & Woodruff 2013 in the past 5 years have addressed androgen actions in the ovary. In this review, we summarize what currently is known about the direct physiological actions of androgens in the regulation of normal follicular development, and provide the molecular and/or signaling basis of these androgen actions.…”

Bringing androgens up a NOTCH in breast cancer

“…Although women produce less androgen hormone than men and metabolize a higher proportion of their androgen to oestrogen, direct androgen activity mediated via the AR influences development of the female phenotype and is important for the healthy functioning of multiple organs in women, including the ovaries (Lebbe & Woodruff 2013, O'Reilly et al 2014, Sen et al 2014, uterus (Wood et al 2009, Cloke & Christian 2012, bone (Watts et al 1995), muscle (Smith et al 2014), adipose tissue (Barbosa-Desongles et al 2013, Chazenbalk et al 2013, and brain (Shifren 2002, Lobo et al 2003, Ryan et al 2009, Zarrouf et al 2009). However, less is known about the mechanisms of AR signalling in female tissues compared with either AR signalling in male target tissues (e.g.…”