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Les récepteurs aux œstrogènes dans le testicule et l’appareil reproducteur du primate et de l’homme

Oestrogen receptors in the human and primate testis and reproductive tract

Resume

L’impact des œstrogènes sur le système reproducteur mâle est le sujet d’intenses débats et l’objet d’une intense activité de recherche. L’action des œstrogènes a lieu par l’intermédiaire de récepteurs intracellulaires de forte affinité, exprimés au niveau des tissus cibles. Deux sous-types de récepteurs aux œstrogènes, connus sous les noms de REα (NR3A1) et REß (NR3A2) ont été clonés, et des isoformes variants de hREß identifiés. Dans les cellules cibles, ces récepteurs peuvent exister sous forme d’homo ou d’hétéro-dimères. Nous avons utilisé une approche immuno-histochimique pour étudier les profils d’expression des RE chez l’homme et les primates non humains comme première étape de la détermination des cibles cellulaires de l’action des œstrogènes chez le mâle.

Le REα a été détecté dans les cellules épithéliales des canaux efférents (CE), occasionnellement dans les cellules de l’épithélium et du stroma épididymaires, mais jamais dans les testicules d’humains ou de primates. En utilisant un anticorps polyclonal contre la région charnière du REß, un marquage immunopositif fut détecté dans de très nombreux types cellulaires dans le testicule, ainsi que dans les noyaux des cellules de l’épithélium et du stroma tout au long de l’appareil reproducteur mâle (CE, épididyme, canal déférent, vésicules séminales, prostate) et dans la vessie. Nous avons aussi utilisé des anticorps monoclonaux qui font la distinction entre la forme complète du type sauvage de REß (REß1), et un isoforme variant tronqué dénommé REßcx/REß2 qui ne se lie pas aux œstrogènes. Les protéines REß1 et REß2 furent toutes les deux détectées dans le testicule humain et possèdent des profils d’expression distincts, mais qui se chevauchent. Le REß1 fut aussi détecté dans les CE, l’épididyme et le canal déférent.

En conclusion, les récepteurs aux œstrogènes sont largement exprimés dans l’appareil urogénital mâle et, à l’exception des CE, il existe plus de cellules exprimant REß que REα. Chez l’homme adulte, les cellules testiculaires qui constituent probablement les cellules cibles des œstrogènes sont les spermatides rondes dans lesquelles les taux d’expression de la forme complète du type sauvage du récepteur (REß1) sont élevés.

Abstract

The impact of oestrogens on the male reproductive system remains the subject of intensive research activity and debate. Oestrogen action is mediated via high affinity intracellular receptors expressed in target tissues. Two subtypes of oestrogen receptor known as REα (NR3A1) and ERß (NR3A2) have been cloned and hERß variant isoforms identified. In target cells these receptors can exist as homo- or heterodimers. We have used immunohistochemistry to examine the patterns of expression of ERs in human and non-human primates as a first step in determining the cellular targets for oestrogen action in the male.

REα was detected in the epithelial cells of efferent ductules (ED) occasionally in epithelial and stromal cells within the epididymis but was undetectable in human or primate testes. Using a polyclonal antibody raised against the hinge domain of ERß, immunopositive staining was detected in multiple cell types within the testis and in epithelial and stromal cell nuclei throughout the male reproductive system (ED, epididymis, vas deferens, seminal vesicles, prostate) and in the bladder. We have also used monoclonal antibodies that distinguish between wild type, full-length ERß (ERß1), and a splice variant isoform called ERßcx/ERß2 that does not bind oestrogens. ERß1 and ERß2 proteins were both detected in human testis and have distinct but overlapping patterns of expression. ERß1 was also detected in ED, epididymis and vas.

In conclusion, oestrogen receptors are widely expressed in the male urogenital system and with the exception of the ED there are more cells that express ERß than REα. In the adult human the testicular cells most likely to be targets for oestrogens are round spermatids in which levels of expression of full-length wild type receptor (ERß1) are high.

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Correspondence to Philippa T. K. Saunders.

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Saunders, P.T.K., Sierens, J.E., Groome, N.P. et al. Les récepteurs aux œstrogènes dans le testicule et l’appareil reproducteur du primate et de l’homme. Androl. 13, 34–42 (2003). https://doi.org/10.1007/BF03034407

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