Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a multifactorial, complex endocrine disorder affecting a significant proportion of the global population. Hyperandrogenism is a key feature of PCOS patients. Aberrant secretion and/or action of gonadotropins have been implicated in PCOS, but, to date, we have only limited knowledge of how these factors may interact in the aetiology of PCOS. We hypothesised that excess androgens may cause aberrant gonadotropin activity and therefore sought to examine the effect of androgen treatment on gonadotropin receptor signalling and function. Granulosa lutein cells (GLC) from women without PCOS were pre-treated with 10nm DHT in vitro for 24 hours prior to luteinizing hormone (LH) treatment. LH receptor (LHCGR) gene expression, downstream signalling and steroid synthesis were evaluated by R-qPCR, cyclic AMP (cAMP) assay, immunofluorescence, and Western blotting. DHT augmented the cAMP response to LH (up to 15-fold change). Increased generation of pERk 1/2 in response to LH was also observed with the addition of DHT. These changes occurred without an increase in LHCGR expression but DHT treatment increased androgen receptor (AR) gene expression. AR expression was, in turn, downregulated by LH treatment in vitro, indicating a functionally significant relationship between these two key receptors. In conclusion, androgens directly contribute to reprogramming LHCGR signalling and function in GLCs and this interaction is relevant to understanding the aetiology of PCOS.