دانلود رایگان مقاله انگلیسی نقش آندروژن در تخمدان - الزویر 2018

Abstract

It has been well established for decades that androgens, namely testosterone (T) plays an important role in female reproductive physiology as the precursor for oestradiol (E2). However, in the last decade a direct role for androgens, acting via the androgen receptor (AR), in female reproductive function has been confirmed. Deciphering the specific roles of androgens in ovarian function has been hindered as complete androgen resistant females cannot be generated by natural breeding. In addition, androgens can be converted into estrogens which has caused confusion when interpreting findings from pharmacological studies, as observed effects could have been mediated via the AR or estrogen receptor. The creation and analysis of genetic mouse models with global and cell-specific disruption of the Ar gene, the sole mediator of pure androgenic action, has now allowed the elucidation of a role for AR-mediated androgen actions in the regulation of normal and pathological ovarian function. This review aims to summarize findings from clinical, animal, pharmacological and novel genetic AR mouse models to provide an understanding of the important roles androgens play in the ovary, as well as providing insights into the human implications of these roles.

7. Conclusions

Data from clinical, pharmacological and genetic studies have now converged to conclusively demonstrate an important role for androgens in the regulation of ovarian function and female fertility. Indirectly, androgens are the obligatory precursor for E2 biosynthesis, which is essential for follicular development and more generally as a substrate for estrogen synthesis and action. A direct role for androgens has also been confirmed with their actions found to be important for optimising follicle growth, follicle health and ovulation. Within the ovary MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT 24 granulosa cells appear to be an important site of action for AR signalling, and in addition, an unexpected role for AR-regulated neuroendocrine control of ovarian function has also been firmly established. Importantly, an optimal balance in the level of androgens present appears to be critical to maintaining normal ovarian function. A reduction in androgenic signalling, as observed in ARKO models, causes subfertility and defective ovarian function. On the other hand, androgen excess in animal models replicates human PCOS characteristics and there is strong evidence to support a direct pathological role for AR-mediated signalling in the development of PCOS (Caldwell et al. 2015; Walters 2015).