Altered Expression of Aromatase, Estrogen Receptors and Progesterone Receptors in Human Leydig Cell Hyperplasia

Candela Rocío González,Roberto Ponzio,Claudio Terradas,Alfredo Daniel Vitullo,Ricardo Saúl Calandra,Elisa Puigdomenech,Pablo Ignacio Felipe Inserra,Oscar Levalle,Silvia Ines Gonzalez-Calvar

doi:10.4236/abb.2015.61001

Candela Rocío González, Roberto Ponzio + Show 7 more

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https://doi.org/10.4236/abb.2015.61001

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Abstract

Testicular function is regulated by pituitary hormones and also by paracrine and autocrine factors. A number of reports have pointed out the importance of estrogens and progesterone in male reproductive tract. Recently, we have reported in testicular biopsies from men with Sertoli Cell Only Syndrome (SCO) or Hypospermatogenesis (H) with Leydig cell hyperplasia (LCH) an increase in the expression of the TGFB1 and its receptors ALK1 and endoglin, which are involved in the proliferation of Leydig cells. The aim of the present work was to analyze the expression of aromatase, estrogen and progesterone receptors (ERs, PR) in pathological testicular biopsies with SCO or H with and without LCH. The ERs and CYP19 proteins were detected in the Leydig cells from all pathological biopsies analyzed. Biopsies with SCO or H with LCH showed an increment in the immunostaining of CYP19 and ERs in the Leydig cells respect to biopsies without LCH. The gene expression of CYP19 was increased in SCO or H biopsies with LCH respect to SCO and H biopsies without LCH. PR was localized in Leydig cells and showed a significant increment in biopsies with LCH respect from biopsies without LCH. The gene expression of both PRA and PRB was increased in biopsies with LCH respect to biopsies without LCH. In concussion, alterations in the gene expression of aromatase, ERs, and PR and the likely interactions of these systems with locally produced factors such as growth factors and cytokines, might lead to Leydig cell proliferation in testicular pathology.

Highlights

Testis exerts two main functions: steroidogenesis and spermatogenesis, which are both finely regulated by endocrine, autocrine and paracrine factors
We studied the differential pattern of expression of the ERα and ERβ isoforms as well as PRA and PRB isoforms and their involvement on Leydig cell hyperplasia
The intensity of aromatase immunostaining in Leydig cells was higher in patients with Leydig cell hyperplasia (LCH) compared with patients without LCH (SCO + LCH vs SCO: 5 fold, p < 0.05; H + LCH vs H: 5.6 fold, p < 0.05)

Summary

Introduction

Testis exerts two main functions: steroidogenesis and spermatogenesis, which are both finely regulated by endocrine, autocrine and paracrine factors. While testosterone is the main steroid produced by testis, estrogens and progesterone are synthesized by male gonads. A number of reports have pointed out the importance of these hormones in male reproductive tract [1]-[4]. The synthesis of estrogens is catalyzed by aromatase enzyme encoded by CYP19 gene. It has been reported that aromatase is expressed in germ cells and spermatids [5], Leydig cells have been identified as the major site of expression in the testis [3] [6] [7]. Aromatase activity has been shown to be controlled by LH, cyclic AMP and testosterone, and by local factors

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