Analysis of androgen receptor and anti-Müllerian hormone pathways in human granulosa cells under luteinizing hormone treatment

Kuo-Chung Lan,Fu-Jen Huang,Ko-En Huang,Ching-Yuang Lin,Hsin-Jung Lin,Hong-Yo Kang,Shiuh Young Chang

doi:10.1186/1477-7827-11-11

Abstract

BackgroundThe objective of this study was to determine the gene expression profiles of the androgen/androgen receptor (AR) and anti-Müllerian hormone (AMH)/ Sry-related high-mobility group box 9 (SOX9) pathways in granulosa-luteal cells from patients undergoing standard in vitro fertilization (IVF) with or without recombinant luteinizing hormone (rLH) therapy.MethodsLevels of reproductive hormones in the pre-ovulatory follicular fluid and the expression levels of LHR (luteinizing hormone receptor), AR, SOX9, AMH, AR-associated protein 54(ARA54)and ARA70 were determined in granulosa-luteal cells by real-time reverse-transcription PCR. The effects of androgen and rLH treatments on AR and AMH expression levels were also tested in vitro using HO23 cells.ResultsWe collected 35 an 70 granulosa cell samples from patients cycled with and without rLH supplementation, respectively. The clinical outcomes were similar in patients who received rLH therapy and those who did not, though the pre-ovulatory follicular fluid levels of androstenedione, testosterone, and estradiol were significantly higher and progesterone was lower in the rLH supplementation group. Moreover, granulosa-luteal cell mRNA levels of LHR, AR, AMH, and SOX9 were significantly higher in the rLH supplementation group relative to the group that did not receive rLH supplementation. In addition, we observed significant correlations between LHR and AR mRNA expression and among AR, AMH, and SOX9 mRNA expression in granulosa-luteal cells from patients undergoing standard IVF treatment.ConclusionsIncreased expression of LHR, AR, AMH, and SOX9 is characteristic of granulosa-luteal cells from IVF/ intracytoplasmic sperm injection (ICSI) patients receiving rLH supplementation.

Highlights

The objective of this study was to determine the gene expression profiles of the androgen/androgen receptor (AR) and anti-Müllerian hormone (AMH)/ Sry-related high-mobility group box 9 (SOX9) pathways in granulosa-luteal cells from patients undergoing standard in vitro fertilization (IVF) with or without recombinant luteinizing hormone therapy
We demonstrated that luteinized granulosa cells from IVF patients supplemented with recombinant luteinizing hormone (rLH) display increased luteinizing hormone receptor (LHR), AR, SOX9, and AMH expression and higher testosterone and androstenedione concentrations in the follicular fluid
Our study showed no significant differences in terms of clinical outcomes with or without rLH supplementation (Table 2), the study was underpowered to look at pregnancy rates between the two groups

Summary

Introduction

The objective of this study was to determine the gene expression profiles of the androgen/androgen receptor (AR) and anti-Müllerian hormone (AMH)/ Sry-related high-mobility group box 9 (SOX9) pathways in granulosa-luteal cells from patients undergoing standard in vitro fertilization (IVF) with or without recombinant luteinizing hormone (rLH) therapy. The role of endogenous luteinizing hormone (LH) levels and the effect of LH on follicular maturation and pregnancy outcome during ovarian stimulation have. A growing body of evidence seems to indicate a beneficial effect of co-treatment with rFSH and rLH, in particular for patients suffering pregnancy loss, poor responders [5,6,7,8] and patients of advanced age who undergo ART [6,9,10,11,12,13]. Several coactivator proteins have been shown to bind steroid receptors and enhance their interaction with basal transcription factors, thereby amplifying the transcriptional activation potential of the receptor. Among these coactivators are the AR-associated protein 54 (ARA54) and ARA70 [17]. We previously proposed the possibility of a transition in androgen action from an enhancer of follicular differentiation (through the AR) to a substrate for estrogen synthesis (through aromatase) at the time of oocyte retrieval [17]

Objectives

Methods

Results

Discussion

Conclusion