Androgen and Luteinizing Hormone Stimulate the Function of Rat Immature Leydig Cells Through Different Transcription Signals.

Xiaoheng Li,Kaimin Yuan,Ren-Shan Ge,Zhijian Su,Yiyan Wang,Ying Zhong,Qiqi Zhu,Zina Wen

doi:10.3389/fendo.2021.599149

Abstract

The function of immature Leydig cells is regulated by hormones, such as androgen and luteinizing hormone (LH). However, the regulation of this process is still unclear. The objective of this study was to determine whether luteinizing hormone (LH) or androgens contribute to this process. Immature Leydig cells were purified from 35-day-old male Sprague Dawley rats and cultured with LH (1 ng/ml) or androgen (7α-methyl-19- nortestosterone, MENT, 100 nM) for 2 days. LH or MENT treatment significantly increased the androgens produced by immature Leydig cells in rats. Microarray and qPCR and enzymatic tests showed that LH up-regulated the expression of Scarb1, Cyp11a1, Cyp17a1, and Srd5a1 while down-regulated the expression of Sult2a1 and Akr1c14. On the contrary, the expression of Cyp17a1 was up-regulated by MENT. LH and MENT regulate Leydig cell function through different sets of transcription factors. We conclude that LH and androgens participate in the regulation of rat immature Leydig cell function through different transcriptional pathways.

Highlights

Testosterone secreted by adult Leydig cells in the testis is the main androgen in the male circulation
This study shows that androgen (MENT) and luteinizing hormone (LH) stimulate the function of immature Leydig cells in rats. androgen (MENT) and LH regulate different sets of transcription factors to control steroidogenesis
LH mainly up-regulates the expression of Cyp11a1, Cyp17a1, and Srd5a1 through Crem1 and Egr1 transcription factors

Summary

Introduction

Testosterone secreted by adult Leydig cells in the testis is the main androgen in the male circulation. Progenitor Leydig cells do not have the last step of androgen synthetic enzyme 17b-hydroxysteroid dehydrogenase 3 (HSD17B3, encoded by Hsd17b3), which can catalyze the conversion of androstenedione to testosterone [7], but have higher androgenmetabolizing enzymes, including steroid 5a-reductase isoform 1 (SRD5A1, encoded Srd5a1) and 3a-hydroxysteroid dehydrogenase (AKR1C14, encoded by Akr1c14), which metabolize androstenedione to androstanedione, and further into androsterone [7]. Immature Leydig cells express the last-step androgen synthetic enzyme HSD17B3 that catalyzes androstenedione into testosterone, which is further converted into 5a-androstane3a,17b-diol (androstanediol, DIOL), because these cells still have high capacity of androgen-metabolic enzymes SRD5A1 and AKR1C14 [7]. The development of adult Leydig cells from progenitor cells includes an increase of androgen synthetic enzymes (CYP11A1, HSD3B1, CYP17A1, and HSD17B3) and a decrease of androgen metabolic enzymes (SRD5A1 and AKR1C14) [7]

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Conclusion