The Mechanism of Androgen Actions in PCOS Etiology.

Valentina Rodriguez Paris,Michael J Bertoldo

doi:10.3390/medsci7090089

Valentina Rodriguez Paris, Michael J Bertoldo

Open Access

https://doi.org/10.3390/medsci7090089

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Journal: Medical Sciences	Publication Date: Aug 28, 2019
Citations: 60	License type: CC BY 4.0

Affiliation: UNSW Sydney

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine condition in reproductive-age women. By comprising reproductive, endocrine, metabolic and psychological features—the cause of PCOS is still unknown. Consequently, there is no cure, and management is persistently suboptimal as it depends on the ad hoc management of symptoms only. Recently it has been revealed that androgens have an important role in regulating female fertility. Androgen actions are facilitated via the androgen receptor (AR) and transgenic Ar knockout mouse models have established that AR-mediated androgen actions have a part in regulating female fertility and ovarian function. Considerable evidence from human and animal studies currently reinforces the hypothesis that androgens in excess, working via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). Identifying and confirming the locations of AR-mediated actions and the molecular mechanisms involved in the development of PCOS is critical to provide the knowledge required for the future development of innovative, mechanism-based interventions for the treatment of PCOS. This review summarises fundamental scientific discoveries that have improved our knowledge of androgen actions in PCOS etiology and how this may form the future development of effective methods to reduce symptoms in patients with PCOS.

Highlights

Polycystic ovary syndrome (PCOS) is a heterogeneous condition, which affects approximately6% to 20% of women of reproductive age
This review summarises fundamental scientific discoveries that have improved our knowledge of androgen actions in PCOS etiology and how this may form the future development of effective methods to reduce symptoms in patients with PCOS
In hyperandrogenized and ovariectomized global androgen receptor knockout (ARKO) mice that received control ovaries containing a functional androgen receptor (AR), PCOS did not develop [45]. These observations further corroborate that extra-ovarian mechanism are the main drivers in the development of PCOS. These findings indicate that while ovarian AR signalling may be involved in the development of reproductive features observed in PCOS, neuroendocrine androgen-driven mechanisms in the brain are the key mediators in the developmental origins of PCOS

Summary

Introduction

Polycystic ovary syndrome (PCOS) is a heterogeneous condition, which affects approximately. Disturbed hormonal and reproductive features include luteinizing hormone (LH) excess, hyperandrogenism, ovulatory perturbations, aberrant follicular development, diminished fertility, and an increased risk of miscarriage [2]. If pregnancy is attained, women with PCOS have a considerably greater risk of pregnancy difficulties, including gestational diabetes, hypertensive disorders and premature delivery [7]. PCOS has a significant metabolic component as it is linked with obesity, metabolic syndrome, hyperinsulinemia, insulin resistance, Med. Sci. The genesis of PCOS continues to evade us; mechanism-based interventions persist elusively. A significant need exists for continuing research to characterise the etiology of PCOS, and deliver the required knowledge for the advancement of mechanism-based directed interventions for this condition

The Relationship between Hyperandrogenism and the Pathophysiology of PCOS

Clinical Targeting of Androgen Excess—Potential for Mitigating Against PCOS

Development of Pre-Clinical Animal Models of PCOS

Neuroendocrine Pathways

Metabolic Pathways

Future Perspectives

Conclusions