Skip to main content
Download PDF
  • Estrogènes et Reproduction chez le Mâle
  • Published:

Les sources d’estrogènes

Sources of estrogens

Andrologie volume 13, pages 22–27 (2003)Cite this article

Resume

Le cytochrome P450 aromatase (P450arom) est l’enzyme qui est responsable de la transformation irréversible des androgènes en estrogènes. Chez l’homme le P450arom est le produit d’un gène uniqueCYP19 localisé sur le chromosome 15 dans la bande q21.1, c’est l’un des plus longs (environ 120 kb) parmi ceux codant pour des enzymes stéroïdiens. Il est composé de 18 exons dont 9 sont codants; ce gène est singulier car il renferme au moins 8 exons non traduits tous situés dans l’extrémité 5’ et épissés après leur transcription en aval d’autant de promoteurs dits «tissu-spécifiques». Les éléments régulateurs diffèrent d’un promoteur à l’autre et l’expression du gène dépend donc de l’environnement cellulaire. Nos résultats et ceux de la littérature démontrent que non seulement les cellules somatiques mais aussi les cellules sexuelles sont capables de produire des estrogènes. Dans le testicule du rat mature, l’expression de l’aromatase est contrôlée par les promoteurs II et I.4. Le taux de transcrits du P450arom est 2 fois plus élevé dans les spermatocytes pachytènes que dans les spermatides rondes alors que la bioactivité de la protéine évolue en sens inverse (elle est 4–5 fois plus importante dans les spermatozoïdes que dans les cellules plus jeunes). Très récemment nous avons démontré que les spermatozoïdes éjaculés chez l’homme renferment une aromatase avec des taux d’ARNm qui varient en fonction de la qualité du spermatozoïde: la quantité de messagers est diminuée de 30% dans les cellules immobiles. Si la testostérone est le médiateur principal du développement testiculaire, les estrogènes produits localement, compte tenu de la présence de récepteurs spécifiques (REα et/ou REβ), sont sans aucun doute impliqués dans le contrôle de la spermatogenèse en agissant soit directement sur les cellules sexuelles soit par l’intermédiaire des cellules somatiques, en particulier au niveau des spermatides et de la maturation du spermatozoïde.

Abstract

The ability of the testis to irreversibly convert androgens into estrogens is related to the presence of a microsomal enzymatic complex called aromatase, which is composed of a specific glycoprotein, cytochrome P450 aromatase (P450arom) and an ubiquitous reductase. In the rat testis, we have immunolocalized P450arom not only in Leydig cells, but also in germ cells and especially in elongated spermatids. We have shown that the level of P450arom mRNA transcripts decreases according to the stage of germ cell maturation and is much higher in younger germ cells than in mature germ cells, while aromatase activity is 2- to 4-fold higher in spermatozoa compared to the other two enriched germ cell preparations. By using anin vitro model of mature rat Leydig cells, pachytene spermatocytes and round spermatids, we have shown that several factors direct the expression of the aromatase gene in these cells and that promoters PII but also PI.4 are clearly involved. Our recent data obtained from ejaculated human spermatozoa demonstrate expression of aromatase both in terms of mRNA and protein, and our results also suggest that aromatase could be involved in the acquisition of sperm motility. Together with the widespread distribution of ERs in testicular cells, these data provide new light on the hormonal regulation of spermatogenesis in mammals.

References

  1. BILINSKA B., SCHMALZ-FRACZEK B., SADOWSKA J., CARREAU S.: Localisation of cytochrome P450 aromatase and oestrogen receptors α and β in bank vole testicular cells. Acta Histochem., 2000, 102: 1–15.

    Article  Google Scholar 

  2. BILINSKA B., SCHMALZ-FRACZEK B., KOTULA M., CARREAU S.: Photoperiod-dependent capability of androgen aromatization and the role of estrogens in bank vole testis visualized by means of immunohistochemistry. Mol. Cell. Endocrinol., 2001, 178: 189–198.

    Article  PubMed  CAS  Google Scholar 

  3. CARREAU S.: Germ cells: a new source of estrogens in the male gonad. Mol. Cell. Endocrinol., 2001, 178: 65–72.

    Article  PubMed  CAS  Google Scholar 

  4. CARREAU S., BOURGUIBA S., LAMBARD S. et al.: Aromatase expression in male germ cells. J. Steroid Biochem. Molec. Biol., 2001, 79: 203–208.

    Article  PubMed  CAS  Google Scholar 

  5. CARREAU S., BOURGUIBA S., LAMBARD S., GALERAUD-DENIS I., GENISSEL C., LEVALLET J.: Reproductive system: aromatase and estrogens, Mol. Cell. Endocrinol., 2002, 193: 137–143.

    Article  PubMed  CAS  Google Scholar 

  6. COUSE J.F., KORACH K.S.: Estrogen receptor null mice: what have we learned and where will they lead us? Endocr. Rev., 1999, 20: 358–417.

    Article  PubMed  CAS  Google Scholar 

  7. DENIS I., MARIE E., CARREAU S.: Estrogènes et spermatozoïde. Andrologie, 1999, 9: 252–260.

    Article  Google Scholar 

  8. FOUCAULT P., DROSDOWSKY M.A., CARREAU S.: Germ cells and Sertoli cells interactions in human testis: evidence for stimulatory and inhibitory effects. Hum. Reprod., 1994, 9: 2062–2068.

    PubMed  CAS  Google Scholar 

  9. GENISSEL C., CARREAU S.: Regulation of the aromatase gene expression in mature rat Leydig cells. Mol. Cell. Endocrinol., 2001, 178: 141–148.

    Article  PubMed  CAS  Google Scholar 

  10. HESS R.A., BUNICK D., LUBAHN D.B., ZHOU Q., BOUMA J.: Morphologic changes in efferent ductules and epididymis in estrogen receptor-α knockout mice. J. Androl., 2000, 21: 107–121.

    PubMed  CAS  Google Scholar 

  11. JANULIS L., BAHR J.M., HESS R.A., JANSSEN S., OSAWA Y., BUNICK D.: Rat testicular germ cells and epididymal sperm contain active P450 aromatase. J. Androl., 1998, 19: 65–71.

    PubMed  CAS  Google Scholar 

  12. LAMBARD, S., GALERAD-DENIS I., BOURAIMA H., BOURGUIBA S., CHOCAT A., CARREAU S.: Cytochrome P450 aromatase expression in ejaculated human spermatozoa. Mol. Hum. Reprod.,soumis pour publication, 2002.

  13. LANZINO M., CATALANO S., GENISSEL C. et al.: Aromatase messenger ribonucleic acid is derived from the proximal promoter of the aromatase gene in Leydig, Sertoli and germ cells of the rat testis. Biol. Reprod., 2001, 64: 1439–1443.

    Article  PubMed  CAS  Google Scholar 

  14. LEVALLET J., BILINSKA B., MITTRE H., GENISSEL C., FRESNEL J., CARREAU S.: Expression and immunolocalization of functional cytochrome P450 aromatase in mature rat testicular cells. Biol. Reprod., 1998, 58: 919–926.

    Article  PubMed  CAS  Google Scholar 

  15. LUCONI M., MURATORI M., FORTI G., BALDI E.: Identification and characterization of a novel functional estrogen receptor on human sperm membrane that interferes with progesterone effects. J. Clin. Endocrinol. Metab., 1999, 84: 1670–1678.

    Article  PubMed  CAS  Google Scholar 

  16. LUCONI M., FORTI G., BALDI E.: Genomic and nongenomic effects of estrogens: molecular mechanisms of action and clinical implications for male reproduction. J. Steroid Biochem. Molec. Biol., 2002, 80: 369–381.

    Article  PubMed  CAS  Google Scholar 

  17. O’DONNELL L., ROBERTSON K.M., JONES M.E.E., SIMPSON E.R.: Estrogen and spermatogenesis. Endocr. Rev., 2001, 22: 289–318.

    Article  PubMed  CAS  Google Scholar 

  18. PELLETIER G., EL-ALFY M.J.: Immunocytochemical localization of estrogen receptors α and β in the human reproductive organs. J. Clin. Endocrinol. Metab., 2000, 85: 4835–4840.

    Article  PubMed  CAS  Google Scholar 

  19. PENTAKAINEN V., ERKKILA K., SUOMALAINEN L., PARVINEN M., DUNKEL L.: Estradiol acts as a germ cell survival factor in the human testis. J. Clin. Endocrinol. Metab., 2000, 85: 2057–2067.

    Article  Google Scholar 

  20. PEREYRA-MARTINEZ A.D., ROSELLI C.E., STADELMAN H.L., RESKO J.A.: Cytochrome P450 aromatase in testis and epididymis of male rhesus monkeys. Endocrine, 2001, 16: 15–19.

    Article  PubMed  CAS  Google Scholar 

  21. ROBERTSON K.M., O’DONNELL L., JONES M.E.E. et al.: Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene. Proc. Natl. Acad. Sc., 1999, 96: 7986–7997.

    Article  CAS  Google Scholar 

  22. ROBERTSON K.M., O’DONNELL L., SIMPSON E.R., JONES M.E.E.: The phenotype of the aromatase knockout mouse reveals dietary phytoestrogens impact significantly on testis function. Endocrinology, 2002, 143: 2913–2921.

    Article  PubMed  CAS  Google Scholar 

  23. SAUNDERS P.T.K., SHARPE R.M., WILLIAMS K.: Differential expression of oestrogen receptor α and β proteins in the testes and male reproductive system of human and non-human primates. Mol. Hum. Reprod., 2001, 7: 227–236.

    Article  PubMed  CAS  Google Scholar 

  24. SEBASTIAN S., BULUN S.E.: A highly complex organization of the regulatory region of the human CYP19 (aromatase) gene revealed by the Human Genome Project. J. Clin. Endocrinol. Metab., 2001, 86: 4600–4602.

    Article  PubMed  CAS  Google Scholar 

  25. SHOZU M., ZHAO Y., SIMPSON E.R.: TGFb1 stimulates expression of the aromatase (CYP19) gene in human osteoblast and THP-1 cells. Mol. Cell. Endocrinol., 2000, 160: 123–133.

    Article  PubMed  CAS  Google Scholar 

  26. SIMPSON E.R., MICHAEL M.D., AGARWAL V.R., HINSHELWOOD M.M., BULUN S.E., ZHAO Y.: Expression of the CYP 19 (aromatase) gene: an unusual case of alternative promoter usage. F.A.S.E.B. J., 1997, 11: 29–36.

    CAS  Google Scholar 

  27. TURNER K.J., MacPHERSON S., MILLAR M.R. et al.: Development and validation of a new monoclonal antibody to mammalian aromatase. J. Endocrinol., 2002, 172: 21–30.

    Article  PubMed  CAS  Google Scholar 

  28. WISZNIEWSKA B.: Primary culture of rat epididymal epithelial cells as a source of estrogen. Andrologia, 2002, 34: 1–8.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biochimie, EA 2608-USC INRA, Université de Caen, Esplanade de la Paix, 14032, Caen Cédex

    Serge Carreau, Sonia Bourguiba, Isabelle Denis-Galeraud & Sophie Lambard

Authors
  1. Serge Carreau
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sonia Bourguiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isabelle Denis-Galeraud
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sophie Lambard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Serge Carreau.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carreau, S., Bourguiba, S., Denis-Galeraud, I. et al. Les sources d’estrogènes. Androl. 13, 22–27 (2003). https://doi.org/10.1007/BF03034405

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03034405

Mots clés

Key-words

Basic and Clinical Andrology

ISSN: 2051-4190