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

œstrogènes et contrôle de la prolifération germinale

Estrogens and germ cell regulation

Andrologie volume 13, pages 28–33 (2003)Cite this article

Resume

L’examen des souris invalidées pour les gènes de l’aromatase ou des récepteurs des estrogènes, les données cliniques d’insuffisance estrogénique primitive chez l’homme par mutation de ces mêmes gènes, les conséquences de l’exposition pré-natale au distilbène*, un estrogène puissant prescrit aux femmes enceintes entre les années 50 et 70, et les données récentes sur les mécanismes d’action des estrogènes, invitent à réévaluer totalement le rôle des hormones stéroïdes dites “féminines” dans la physiologie de la reproduction masculine. Il apparaît ainsi vraisemblable qu’une balance androgènes/estrogène appropriée soit nécessaire à la fois au cours de la différentiation sexuelle, à la descente testiculaire, à la préparation périnatale de la spermatogenèse et à son plein développement à l’âge adulte, ainsi qu’à la maturation des spermatozoïdes d’autant que le testicule exprime à la fois l’aromatase et les récepteurs REα et REβ. Ces différents éléments rendent plausibles l’hypothèse du rôle des perturbateurs endocriniens environnementaux de type xénoestrogènes dans la baisse de la fertilité masculine, l’augmentation des malformations des organes génitaux et du cancer du testicule, et justifient les essais de validation scientifique. Mais les mécanismes d’action précis des estrogènes dans la physiologie de la reproduction masculine et ses perturbations restent encore très imparfaitement caractérisés.

Abstract

The role of so-called female sex steroids in males needs to be completely re-evaluated in the light of the clinical features of male estrogen deficiency, new mechanisms of estrogen receptors, and description of mice lacking functional aromatase or estrogen receptor gene. An appropriate balance between estrogens and androgens appears to be necessary to allow full sexual development and reproduction. All these characteristics support the hypothesis of the role of endocrine disruptors and justify investigation of the possible role of environmental xenoestrogens on male fertility, genital malformations or cancer.

References

  1. ATANASSOVA N., MCKINNEL C., TURNER K.J., et al.: Comparative effects of neonatal exposure of male rats to potent and weak (environnemental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels. Endocrinology, 2000, 141: 3898–3907.

    Article  PubMed  CAS  Google Scholar 

  2. ATANASSOVA N., MCKINNEL C., TURNER K.J. et al.: Permanent effects of neonatal estrogen exposure in rats on reproductive hormone levels, Sertoli cell number, and the efficiency of spermatogenesis in adulthood. Endocrinology, 1999, 140: 5364–5373.

    Article  PubMed  CAS  Google Scholar 

  3. CARANI C., QIN K., SIMONI M., et al.: Effect of testosterone and estradiol in a man with aromatase deficiency. N. Engl. J. Med., 1997, 337: 91–95.

    Article  PubMed  CAS  Google Scholar 

  4. CARLSEN E., GIWERCMAN A., KEIDING N., SKAKKEBAECK N.: Evidence for decreasing quality of semen during past 50 years. Brit. Med. J., 1992, 305: 609–613.

    Article  PubMed  CAS  Google Scholar 

  5. CARREAU S.: Estrogènes et fonctions testiculaires. Reprod. Hum. Hormon., 2000, 13: 1–10.

    Google Scholar 

  6. CARREAU S., BOURGUIBA S., GALERAUD-DENIS I. et al.: Aromatase expression in male germ cells. J. Steroid. Biochem. Mol. Biol. 2001, 79: 203–208.

    Article  PubMed  CAS  Google Scholar 

  7. CHENG C.Y., BOETTCHER B.: The effects of steroids on the in vitro migration of washed human spermatozoa in modified tyrode’s solution or in fasting human blood serum. Fertil. Steril., 1979, 32: 566–570.

    PubMed  CAS  Google Scholar 

  8. 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 

  9. DELADOEY J., FLÜCK C., BEX M., YOSHIMURA N., HARADA N., MULLIS P.: Aromatase deficiency caused by a novel P450arom gene mutation: impact of absent estrogen production on serum gonadotropin concentration in a boy. J. Clin. Endocrinol. Metab., 1999, 84: 4050–4054.

    Article  PubMed  CAS  Google Scholar 

  10. DORRINGTON J.H., BENDELL J.J., KHAN S.A.: Interactions between FSH, estradiol-17β and transforming growth factor-regulate growth and differentiation in the rat gonad. J. Steroid. Biochem. Mol. Biol., 1993, 44: 441–447.

    Article  PubMed  CAS  Google Scholar 

  11. ENMARK E., PELTO-HUIKKO M., GRANDDIEN K. et al.: Human estrogen receptor ßgene structure, chromosomal localization, and expression pattern. J. Clin. Endocrinol. Metab., 1997, 82: 4258–4265.

    Article  PubMed  CAS  Google Scholar 

  12. FAUSTINI-FUSTINI M., ROCHIRA V., CARANI C.: Oestrogen deficiency in men: where are we today? Eur. J. Endocrinol., 1999, 140: 111–129.

    Article  PubMed  CAS  Google Scholar 

  13. FENICHEL P. et al.: Mises au point cliniques d’endocrinologie. In: N. Guétitée et J. Leclère eds. Nutrition et Métabolisme, Paris, 2002: 133–141.

  14. FENICHEL P.: Le point sur hormones et imposteurs endocriniens dans l’eau et la chaîne alimentaire: impact possible en clinique et reproduction humaine. Comte Rendu du Workshop de Risghospitalet: Copenhagen 27–30 Mai 2000. pp20. Ipsen Biotech.

  15. FINKELSTEIN J.S., WHITCOMB R.W., O’DEA L.S., LONSCOPE C., SHOENFELD D.A., CROWLEY W.F. Jr.: Sex steroid control of gonadotrophin secretion in the human male. I: Effect of testosterone administration in normal and gonadotropin-releasing hormone-deficient men. J. Clin. Endocrinol. Metab., 1991, 73: 609–620.

    PubMed  CAS  Google Scholar 

  16. FISHER J.S., TURNER K.J., FRASER H.M., SAUNDERS P.T.K., BROWN D., SHARPE R.M.: Immunoexpression of aquaporin-1 in the efferent ducts of the rat and marmoset monkey during development, its modulation by estrogens, and its possible role in fluid resorption. Endocrinology., 1998, 139: 3935–3945.

    Article  PubMed  CAS  Google Scholar 

  17. GALERAUD-DENIS I., MARIE E., CARREAU S.: Estrogènes et spermatozoïdes. Andrologie, 1999, 9: 252–260.

    Article  Google Scholar 

  18. GILL W.B., SCHUMACHER G.F., BIBBO M., SRAUS F.H.D., SHOENBERG H.W.: Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and semen abnormalities. J. Urol., 1979, 122: 36–39.

    PubMed  CAS  Google Scholar 

  19. GRAY L.E. Jr.: Xenoendocrine disrupters: laboratory studies on male reproductive effects. Toxicol. Lett., 1998, 102: 331–335.

    Article  PubMed  Google Scholar 

  20. HESS R.A., BUNICK D., LEE K.H. et al.: A role for estrogens in the male reproductive system. Nature, 1997, 390: 509–512.

    Article  PubMed  CAS  Google Scholar 

  21. KELLY M., LEVIN E.R.: Rapid actions on plasma membrane estrogen receptors. Trends Endocrinol. Metab., 2001, 12: 152–156.

    Article  PubMed  CAS  Google Scholar 

  22. KREJE J.H., HODGIN J.B., COUSE J.F. et al.: Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc. Natl. Acad. Sci., 1998, 22: 15677–15682.

    Article  Google Scholar 

  23. KUIPER G., ENMARK E., PELTO-HUIKKO M., NILSSON S., GUSTAFSSON J.A.: Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci., 1996, 93: 5925–5930.

    Article  PubMed  CAS  Google Scholar 

  24. LI H., PAPADOPOULOS V., VIDIC B., et al.: Regulation of rat testis gonocyte proliferation by platelet-derived growth factor and estradiol: identification of signaling mechanisms involved. Endocrinology, 1997, 138: 1289–1298.

    Article  PubMed  CAS  Google Scholar 

  25. LUBOSHITZKY R., SHEN-ORR Z., HERER P.: Seminal plasma melatonin and gonadal steroids concentration in normal men. Arch. Androl., 2002, 48: 225–232.

    Article  PubMed  CAS  Google Scholar 

  26. 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. Mol. Biol., 2002, 80: 369–381.

    Article  PubMed  CAS  Google Scholar 

  27. 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 

  28. MACCALMAN C.D., GETSIOS S., FARROOKHI R., BLASHUK O.W.: Estrogens potentiate the stimulatory effects of follicle-stimulating hormone on N-cadherin messenger ribonucleic acid levels in cultured mouse Sertoli cells. Endocrinology, 1997, 138: 41–48.

    Article  PubMed  CAS  Google Scholar 

  29. MAHATO D., GOULDING E.H., KORACH K.S., EDDY E.M.: Spermatogenic cells do not require estrogen receptor a for development or function. Endocrinology, 2000, 141: 1273–1276.

    Article  PubMed  CAS  Google Scholar 

  30. MÄKINEN S., MÄKELÄ S., WEIHUA Z., et al.: Localization of estrogen receptors alpha and beta in human testis. Mol. Hum. Reprod., 2001, 7: 497–503.

    Article  PubMed  Google Scholar 

  31. MIURA T., MIURA C., OHTA T., NADER M.R., TODO T., YAMAUCHI K.: Estradiol-17β stimulates the renewal of spermatogonial stem cells in males. Biochem. Biophys. Res. Commun., 1999, 264: 230–234.

    Article  PubMed  CAS  Google Scholar 

  32. MOREAU F., PURA M., MITTRE H., REZNIK Y., CARREAU S., KOTTLER M.L.: Déficit en estrogènes par mutation inactivatrice du gène de l’aromatase chez l’homme. Ann. Endocrinol., 2002, 63: 269.

    Google Scholar 

  33. MORISHIMA A., GRUMBACH M.M., SIMPSON E.R., FISHER C., QIN K.: Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J. Clin. Endocrinol. Metab., 1995, 80: 3689–3690.

    Article  PubMed  CAS  Google Scholar 

  34. NEF S., SHIPMAN T., PARADA L.F.: A molecular basis for estrogen-induced cryptorchidism. Dev. Biol., 2000, 224: 354–361.

    Article  PubMed  CAS  Google Scholar 

  35. NITTA H., BUNICK D., HESS R.A., et al.: Germ cells of the mouse testis express P450 aromatase. Endocrinology, 1993, 132: 1396–1341.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  38. PERRYMAN K.J., STANTON P.G., LOVELAND K.L., MACLACHLAN R.I., ROBERTSON D.M.: Hormonal dependency of neural cadherin in the binding of round spermatids to Sertoli cells in vitro. Endocrinology, 1996, 137: 3877–3883.

    Article  PubMed  CAS  Google Scholar 

  39. LI H., PAPADOPOULOS V., VIDIC B., DYM M., CULTY M.: Regulation of rat testis gonocyte proliferation by platelet-derived growth factor and estradiol: identification of signaling mechanisms involved. Endocrinology, 1997, 138: 1289–1298.

    Article  PubMed  CAS  Google Scholar 

  40. 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. Sci., 1999, 96: 7986–7991.

    Article  PubMed  CAS  Google Scholar 

  41. ROGER C., MOGHRABI B., CHEVALLIER D. et al.: Le cancer du testicule est-il un cancer estrogèno-dépendant? Effets des estrogènes sur la prolifération des cellules séminomateuses. Ann. Endocrinol., 2002, 63: 350.

    Google Scholar 

  42. SAUNDERS P.T., SHARPE R.M., WILLIAMS K. et al.: Differential expression of estrogen receptor α and β proteins in the testes and male reproductive system of human and non-human primates. Mol. Hum. Reprod., 2000, 7: 227–236.

    Article  Google Scholar 

  43. SHARPE R.M., ATANASSOVA N., MCKINNELL C. et al.: Abnormalities in functional development of the Sertoli cells in rats treated neonatally with diethylstilbestrol: a possible role for estrogens in Sertoli cell development. Biol. Reprod., 1998, 59: 1084–1094.

    Article  PubMed  CAS  Google Scholar 

  44. SHETTY G., KRISHNAMURTY H., KRISHNAMURTY H.N., BHATNAGAR A.S., MOUDGAL N.R.: Effect of long term treatment with aromatase inhibitor on testicular function of adult male Bonnet monkeys (M.Radiata). Steroids, 1998, 63: 414–420.

    Article  PubMed  CAS  Google Scholar 

  45. SMITH E.P., BOYD J., FRANK R., TAKAHASHI H., COHEN R.M., SPEKER B.: Estrogen reistance caused by a mutation in the estrogen-receptor gene in a man. N. Engl. J. Med., 1994, 331: 1056–1061.

    Article  PubMed  CAS  Google Scholar 

  46. TOPPARI J., LARSEN J.C., CHRISTIANSEN P. et al.: Male reproductive health and environmental xenoestrogens. Environ. Health Perspect., 1996, 104: 741–803.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service d’Endocrinologie et Médecine de la Reproduction, INSERM EMI 00-09, Nice

    Patrick Fenichel

Authors
  1. Patrick Fenichel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick Fenichel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fenichel, P. œstrogènes et contrôle de la prolifération germinale. Androl. 13, 28–33 (2003). https://doi.org/10.1007/BF03034406

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03034406

Mots clefs

Key-words

Basic and Clinical Andrology

ISSN: 2051-4190