Correlation Networks Provide New Insights into the Architecture of Testicular Steroid Pathways in Pigs.

Annie Robic,Sarah Djebali,Katia Feve,Thomas Faraut,Catherine Larzul,Laurence Liaubet,Armelle Prunier

doi:10.3390/genes12040551

Abstract

Steroid metabolism is a fundamental process in the porcine testis to provide testosterone but also estrogens and androstenone, which are essential for the physiology of the boar. This study concerns boars at an early stage of puberty. Using a RT-qPCR approach, we showed that the transcriptional activities of several genes providing key enzymes involved in this metabolism (such as CYP11A1) are correlated. Surprisingly, HSD17B3, a key gene for testosterone production, was absent from this group. An additional weighted gene co-expression network analysis was performed on two large sets of mRNA-seq to identify co-expression modules. Of these modules, two containing either CYP11A1 or HSD17B3 were further analyzed. This comprehensive correlation meta-analysis identified a group of 85 genes with CYP11A1 as hub gene, but did not allow the characterization of a robust correlation network around HSD17B3. As the CYP11A1-group includes most of the genes involved in steroid synthesis pathways (including LHCGR encoding for the LH receptor), it may control the synthesis of most of the testicular steroids. The independent expression of HSD17B3 probably allows part of the production of testosterone to escape this control. This CYP11A1-group contained also INSL3 and AGT genes encoding a peptide hormone and an angiotensin peptide precursor, respectively.

Highlights

The regulation of the synthesis of testicular steroids is of major importance in boars, for the control of reproduction and for the specific problem of boar taint [1]
AR appeared significantly correlated with HSD17B3 and FSH receptor (FSHR) (Figure 1)7. of 21 Most of the other correlations which were not reported in Figure 1 are very weak, except for a strong correlation between INHA and HSD3B1 (r = 0.74)
Many genes are coding for key enzymes (AKR1C4, CYP11A1, CYP17A1, CYP19A, HSD17B4, STAR, etc.) of the steroid biosynthesis pathways

Summary

Introduction

The regulation of the synthesis of testicular steroids is of major importance in boars, for the control of reproduction and for the specific problem of boar taint [1]. Production of sex steroids by Leydig cells is, at least in part, under the endocrine control of both gonadotropins (LH and FSH) and under the paracrine control of testosterone and estradiol [2] The action of these hormones is mediated by their specific receptors (encoded by LHCGR, FSHR, AR and ESR1/ESR2 genes, respectively). The 5α reduction of testosterone to dihydrotestosterone (DHT) has never been described in porcine testes [9] With these numerous features relative to endocrine functions, it is not surprising that boars differ from other mammals in terms of testicular morphology: The volume percentage of Leydig cells per whole testis of mature boars is very high [10]

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Conclusion