Androgen Actions and the Ovary

Abstract

Although androgens and the androgen receptor (AR) have defining roles in male reproductive development and function, previously no role in female reproductive physiology beyond testosterone (T) as the precursor in estradiol (E(2)) biosynthesis was firmly established. Understanding the role and specific mechanisms of androgen action via the AR in the ovary has been limited by confusion on how to interpret results from pharmacological studies, because many androgens can be metabolized in vivo and in vitro to steroids that can also exert actions via the estrogen receptor (ESR). Recent genetic studies using mouse models with specific disruption of the Ar gene have highlighted the role that AR-mediated actions play in maintaining female fertility through key roles in the regulation of follicle health, development, and ovulation. Furthermore, these genetic studies have revealed that AR-mediated effects influence age-related female fertility, possibly via mechanisms acting predominantly at the hypothalamic-pituitary axis in a dose-dependent manner. This review focuses on combining the findings from pharmacological studies and novel genetic mouse models to unravel the roles of ovarian androgen actions in relation to female fertility and ovarian aging, as well as creating new insights into the role of androgens in androgen-associated reproductive disorders such as polycystic ovarian syndrome.

Molecular aspects of bovine cystic ovarian disease pathogenesis

“…This increase would be associated with the role of androgens in follicular differentiation and growth (Hillier & Tetsuka 1997, Vendola et al 1998, Walters et al 2008. Furthermore, there are discrepancies between AR mRNA and protein expression, which could be explained by post-translational regulation (Sette et al 2010, Salvetti et al 2012.…”

“…stage of development, modifications in intrafollicular activity of steroid hormones determine the fate of a specific follicle (Rosenfeld et al 2001, Drummond et al 2002, Walters et al 2008.…”

Androgen actions in the ovary: balance is key

“…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.…”

Revisiting the Role of Antiandrogen Strategies in Ovarian Cancer

“…In women, androgens are mainly synthesized in the adrenal glands, the ovaries, and adipose tissue, and they have an important physiological significance for bone and muscle growth and maintenance as well as cognitive function [1,5]. There is a growing body of evidence supporting the notion that androgens influence proliferation of the normal ovarian epithelium and are a risk factor for EOC [6].…”

“…The androgen receptor (AR) is a nuclear receptor that functions as an androgen-dependent transcriptional regulator [1,2]. In its basal state, AR is inactive and is bound to heatshock proteins and other cellular chaperones.…”