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. 1996 May;148(5):1689–1698.

Testicular dysgenesis does not affect expression of anti-müllerian hormone by Sertoli cells in premeiotic seminiferous tubules.

R Rey 1, L al-Attar 1, F Louis 1, F Jaubert 1, P Barbet 1, C Nihoul-Fékété 1, J L Chaussain 1, N Josso 1
PMCID: PMC1861550  PMID: 8623936

Abstract

Anti-Müllerian hormone (AMH) immunoreactivity was studied on paraffin sections obtained from archival testicular biopsies of 29 children with intersex disorders and of 22 controls. Strong AMH immunoreactivity was observed in Sertoli cell cytoplasm from 8 fetal weeks until puberty. During pubertal maturation, in both normal and intersex patients, AMH expression was present in premeiotic seminiferous tubules, but was no longer detected in neighboring tubules with meiotic development. AMH immunostaining was abolished in the testis of one patient with persistent Müllerian ducts due to a mutation of the AMH gene, but was conserved in the testes of two patients with mutations of the AMH receptor gene. Testicular dysgenesis usually results in sexual ambiguity, with low testosterone and AMH serum levels and persistence of Müllerian derivatives. AMH immunoreactivity was conserved in premeiotic seminiferous tubules of dysgenetic testes, and also in sex-cord cells of a gonadoblastoma. In patients with asymmetric gonadal differentiation, the streak gonad was AMH-negative. In conclusion, secretion of AMH is a constitutive feature of the immature Sertoli cell and its expression is altered only by mutations of the AMH gene, but not by gonadal dysgenesis. The degree of regression of Müllerian ducts and serum AMH levels reflect the number, not the functional value, of Sertoli cells present in the immature testis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BERGADA C., CLEVELAND W. W., JONES H. W., Jr, WILKINS L. Gonadal histology in patients with male pseudohermaphroditism and atypical gonadal dysgenesis: relation to theories of sex differentiation. Acta Endocrinol (Copenh) 1962 Aug;40:493–520. doi: 10.1530/acta.0.0400493. [DOI] [PubMed] [Google Scholar]
  2. Baker M. L., Metcalfe S. A., Hutson J. M. Serum levels of müllerian inhibiting substance in boys from birth to 18 years, as determined by enzyme immunoassay. J Clin Endocrinol Metab. 1990 Jan;70(1):11–15. doi: 10.1210/jcem-70-1-11. [DOI] [PubMed] [Google Scholar]
  3. Bremner W. J., Millar M. R., Sharpe R. M., Saunders P. T. Immunohistochemical localization of androgen receptors in the rat testis: evidence for stage-dependent expression and regulation by androgens. Endocrinology. 1994 Sep;135(3):1227–1234. doi: 10.1210/endo.135.3.8070367. [DOI] [PubMed] [Google Scholar]
  4. Eicher E. M. Sex and trinucleotide repeats. Nat Genet. 1994 Mar;6(3):221–223. doi: 10.1038/ng0394-221. [DOI] [PubMed] [Google Scholar]
  5. Gustafson M. L., Lee M. M., Scully R. E., Moncure A. C., Hirakawa T., Goodman A., Muntz H. G., Donahoe P. K., MacLaughlin D. T., Fuller A. F., Jr Müllerian inhibiting substance as a marker for ovarian sex-cord tumor. N Engl J Med. 1992 Feb 13;326(7):466–471. doi: 10.1056/NEJM199202133260707. [DOI] [PubMed] [Google Scholar]
  6. Hudson P. L., Dougas I., Donahoe P. K., Cate R. L., Epstein J., Pepinsky R. B., MacLaughlin D. T. An immunoassay to detect human müllerian inhibiting substance in males and females during normal development. J Clin Endocrinol Metab. 1990 Jan;70(1):16–22. doi: 10.1210/jcem-70-1-16. [DOI] [PubMed] [Google Scholar]
  7. Imbeaud S., Carré-Eusèbe D., Rey R., Belville C., Josso N., Picard J. Y. Molecular genetics of the persistent müllerian duct syndrome: a study of 19 families. Hum Mol Genet. 1994 Jan;3(1):125–131. doi: 10.1093/hmg/3.1.125. [DOI] [PubMed] [Google Scholar]
  8. Imbeaud S., Faure E., Lamarre I., Mattéi M. G., di Clemente N., Tizard R., Carré-Eusèbe D., Belville C., Tragethon L., Tonkin C. Insensitivity to anti-müllerian hormone due to a mutation in the human anti-müllerian hormone receptor. Nat Genet. 1995 Dec;11(4):382–388. doi: 10.1038/ng1295-382. [DOI] [PubMed] [Google Scholar]
  9. Josso N., Cate R. L., Picard J. Y., Vigier B., di Clemente N., Wilson C., Imbeaud S., Pepinsky R. B., Guerrier D., Boussin L. Anti-müllerian hormone: the Jost factor. Recent Prog Horm Res. 1993;48:1–59. doi: 10.1016/b978-0-12-571148-7.50005-1. [DOI] [PubMed] [Google Scholar]
  10. Josso N., Lamarre I., Picard J. Y., Berta P., Davies N., Morichon N., Peschanski M., Jeny R. Anti-müllerian hormone in early human development. Early Hum Dev. 1993 Jun;33(2):91–99. doi: 10.1016/0378-3782(93)90204-8. [DOI] [PubMed] [Google Scholar]
  11. Josso N., Legeai L., Forest M. G., Chaussain J. L., Brauner R. An enzyme linked immunoassay for anti-müllerian hormone: a new tool for the evaluation of testicular function in infants and children. J Clin Endocrinol Metab. 1990 Jan;70(1):23–27. doi: 10.1210/jcem-70-1-23. [DOI] [PubMed] [Google Scholar]
  12. Josso N., Picard J. Y., Trah D. The antimüllerian hormone. Recent Prog Horm Res. 1976;33:117–167. doi: 10.1016/b978-0-12-571133-3.50011-8. [DOI] [PubMed] [Google Scholar]
  13. Jégou B. The Sertoli-germ cell communication network in mammals. Int Rev Cytol. 1993;147:25–96. [PubMed] [Google Scholar]
  14. Kremer H., Kraaij R., Toledo S. P., Post M., Fridman J. B., Hayashida C. Y., van Reen M., Milgrom E., Ropers H. H., Mariman E. Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet. 1995 Feb;9(2):160–164. doi: 10.1038/ng0295-160. [DOI] [PubMed] [Google Scholar]
  15. Lee M. M., Donahoe P. K. Mullerian inhibiting substance: a gonadal hormone with multiple functions. Endocr Rev. 1993 Apr;14(2):152–164. doi: 10.1210/edrv-14-2-152. [DOI] [PubMed] [Google Scholar]
  16. Lin D., Sugawara T., Strauss J. F., 3rd, Clark B. J., Stocco D. M., Saenger P., Rogol A., Miller W. L. Role of steroidogenic acute regulatory protein in adrenal and gonadal steroidogenesis. Science. 1995 Mar 24;267(5205):1828–1831. doi: 10.1126/science.7892608. [DOI] [PubMed] [Google Scholar]
  17. Müller J., Torsson A., Damkjaer Nielsen M., Petersen K. E., Christoffersen J., Skakkebaek N. E. Gonadal development and growth in 46,XX and 46,XY individuals with P450scc deficiency (congenital lipoid adrenal hyperplasia). Horm Res. 1991;36(5-6):203–208. doi: 10.1159/000182162. [DOI] [PubMed] [Google Scholar]
  18. Münsterberg A., Lovell-Badge R. Expression of the mouse anti-müllerian hormone gene suggests a role in both male and female sexual differentiation. Development. 1991 Oct;113(2):613–624. doi: 10.1242/dev.113.2.613. [DOI] [PubMed] [Google Scholar]
  19. Nistal M., Abaurrea M. A., Paniagua R. Morphological and histometric study on the human Sertoli cell from birth to the onset of puberty. J Anat. 1982 Mar;134(Pt 2):351–363. [PMC free article] [PubMed] [Google Scholar]
  20. Rajfer J., Mendelsohn G., Arnheim J., Jeffs R. D., Walsh P. C. Dysgenetic male pseudohermaphroditism. J Urol. 1978 Apr;119(4):525–527. doi: 10.1016/s0022-5347(17)57536-9. [DOI] [PubMed] [Google Scholar]
  21. Rajpert-De Meyts E., Skakkebaek N. E. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours. Int J Androl. 1994 Apr;17(2):85–92. doi: 10.1111/j.1365-2605.1994.tb01225.x. [DOI] [PubMed] [Google Scholar]
  22. Rey R., Lordereau-Richard I., Carel J. C., Barbet P., Cate R. L., Roger M., Chaussain J. L., Josso N. Anti-müllerian hormone and testosterone serum levels are inversely during normal and precocious pubertal development. J Clin Endocrinol Metab. 1993 Nov;77(5):1220–1226. doi: 10.1210/jcem.77.5.8077315. [DOI] [PubMed] [Google Scholar]
  23. Rey R., Mebarki F., Forest M. G., Mowszowicz I., Cate R. L., Morel Y., Chaussain J. L., Josso N. Anti-müllerian hormone in children with androgen insensitivity. J Clin Endocrinol Metab. 1994 Oct;79(4):960–964. doi: 10.1210/jcem.79.4.7962305. [DOI] [PubMed] [Google Scholar]
  24. Rutgers J. L., Scully R. E. The androgen insensitivity syndrome (testicular feminization): a clinicopathologic study of 43 cases. Int J Gynecol Pathol. 1991;10(2):126–144. doi: 10.1097/00004347-199104000-00002. [DOI] [PubMed] [Google Scholar]
  25. SOHVAL A. R. HERMAPHRODITISM WITH "ATYPICAL" OR "MIXED" GONADAL DYSGENESIS. RELATIONSHIP TO GONADAL NEOPLASM. Am J Med. 1964 Feb;36:281–292. doi: 10.1016/0002-9343(64)90091-9. [DOI] [PubMed] [Google Scholar]
  26. Sar M., Lubahn D. B., French F. S., Wilson E. M. Immunohistochemical localization of the androgen receptor in rat and human tissues. Endocrinology. 1990 Dec;127(6):3180–3186. doi: 10.1210/endo-127-6-3180. [DOI] [PubMed] [Google Scholar]
  27. Scully R. E. Gonadoblastoma. A review of 74 cases. Cancer. 1970 Jun;25(6):1340–1356. doi: 10.1002/1097-0142(197006)25:6<1340::aid-cncr2820250612>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  28. Shan L. X., Zhu L. J., Bardin C. W., Hardy M. P. Quantitative analysis of androgen receptor messenger ribonucleic acid in developing Leydig cells and Sertoli cells by in situ hybridization. Endocrinology. 1995 Sep;136(9):3856–3862. doi: 10.1210/endo.136.9.7649092. [DOI] [PubMed] [Google Scholar]
  29. Shen W. H., Moore C. C., Ikeda Y., Parker K. L., Ingraham H. A. Nuclear receptor steroidogenic factor 1 regulates the müllerian inhibiting substance gene: a link to the sex determination cascade. Cell. 1994 Jun 3;77(5):651–661. doi: 10.1016/0092-8674(94)90050-7. [DOI] [PubMed] [Google Scholar]
  30. Taketo T. Production of müllerian-inhibiting substance (MIS) and sulfated glycoprotein-2 (SGP-2) associated with testicular differentiation in the XX mouse gonadal graft. Ann N Y Acad Sci. 1991;637:74–89. doi: 10.1111/j.1749-6632.1991.tb27302.x. [DOI] [PubMed] [Google Scholar]
  31. Ueno S., Takahashi M., Manganaro T. F., Ragin R. C., Donahoe P. K. Cellular localization of müllerian inhibiting substance in the developing rat ovary. Endocrinology. 1989 Feb;124(2):1000–1006. doi: 10.1210/endo-124-2-1000. [DOI] [PubMed] [Google Scholar]
  32. Wilson J. D. Syndromes of androgen resistance. Biol Reprod. 1992 Feb;46(2):168–173. doi: 10.1095/biolreprod46.2.168. [DOI] [PubMed] [Google Scholar]

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