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Hormonelle Grundlagen der normalen und pathologischen somatischen Sexualentwicklung

Basic hormonal mechanisms of normal and pathological somatic sexual differentiation

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Summary

Normal sexual development is the consequence of three sequential interrelated processes: establishment of genetic, gonadal and somatic sex. It is the terminal phase of sexual differentiation-the translation of gonadal into somatic sex, which is governed by the presence or absence of both testosterone and Müllerian-inhibiting hormone and of dihydrotestosterone, which is formed in its respective target tissues. Thus, despite a testis, somatic male sexual differentiation will proceed to a normal male phenotype only if all three hormones are synthesized and act during a critical period of uterine development. Many clinically distinct syndromes are the results of abnormalities in the synthesis or action of the above-mentioned hormones; these syndromes are described in detail. In contrast to male somatic differentiation, female somatic development is independent of these hormones.

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Abbreviations

DHT:

5α-Dihydrotestosteron

HY-Antigen:

Histocompatibilitätsantigen-Y

MIH:

Müllerian-Inhibiting-Hormon

SSW:

Schwangerschaftswoche

Literatur

  1. Ainsworth L, Daenen M, Ryan KJ (1969) Steroid hormone transformations by endocrine organs from pregnant mammals. IV. Biosynthesis and metabolism of estrogens and progesterone by primate placental preparations in vitro. Endocrinology 84:1421–1429

    PubMed  Google Scholar 

  2. Anderson DC (1974) Sex-hormone-binding globuline. Clin Endocrinol 3:69–96

    Google Scholar 

  3. Bidlingmaier F, Knorr D, Neumann F (1977) Inhibition of masculine differentiation in male offspring of rabbits actively immunised against testosterone before pregnancy. Nature 266:647–648

    PubMed  Google Scholar 

  4. Bidlingmaier F, Knorr D, Neumann F (1980) Antibodies against testosterone: valuable tools for the investigation of the hypothalamo-pituitary-gonadal system in the rabbit fetus. Hormone Res 13:16–27

    PubMed  Google Scholar 

  5. Biglieri EG, Herron MA, Brust N (1966) 17β-hydroxylation deficiency in man. J Clin Invest 45:1946–1954

    PubMed  Google Scholar 

  6. Bolté E, Mancuso S, Dray F, Beaulieu EE, Diczfalusy E (1964) Conversion of testosterone-17-3H into 17β-estradiol-17-3H by human placentas perfused in situ. Steroids 4:613–623

    Google Scholar 

  7. Bongiovanni AM (1961) Unusual steroid pattern in congenital adrenal hyperplasia: deficiency of 3β-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab 21:860–862

    Google Scholar 

  8. Bongiovanni AM (1972) Disorders of adrenocortical steroid biogenesis. In: Stanbury JB, Wyngaarden JB, Frederickson DS (eds) The metabolic basis of inherited disease. 3rd ed., McGraw-Hill, New York, pp 857–885

    Google Scholar 

  9. Bongiovanni AM (1978) Congenital adrenal hyperplasia and related disorders. In: Stanbury JB, Wyngaarden JB, Frederickson, DS (eds) The metabolic basis of inherited disease. 4th ed. McGraw-Hill, New York, pp 868–893

    Google Scholar 

  10. Bouin P, Ancel P (1903) Sur la signification de la glande interstitielle du testicule embryonnaire. CR Soc Biol 55:1682–1684

    Google Scholar 

  11. Brook CGD, Wagner H, Zachmann M (1973) Familial occurrence of persistent müllerian structures in otherwise normal males. Br Med J 1:771–773

    PubMed  Google Scholar 

  12. Crawford JD, Adams RD, Kliman B, Federman DD, Ulfelder HS, Holmes LB (1970) Syndromes of testicular feminization: an informal apraisal and review of the latest advances in insights, with special emphasis on pathogenesis, biochemical mechanism at work and psychosocial clinical problems. Clin Pediatr 9:165–178

    Google Scholar 

  13. Federman DD (1967) Abnormal sexual development; a genetic and endocrine aproach to differential diagnosis. Philadelphia W.B. Saunders, pp 121–133

    Google Scholar 

  14. Gilbert-Dreyfus S, Sébaoun CA, Belaisch J (1957) Etude d'un cas familial d'androgynoidisme avec hypospadias grave, gynécomastie et hyperoestrogénie. Ann Endocrinol 18:93–101

    Google Scholar 

  15. Gillman J (1948) The development of the gonads in man, with a consideration of the role of fetal endocrines and the histogenesis of ovarian tumors. Carnegie Contrib Embryol No. 210, 32:83–131

    Google Scholar 

  16. Goldman AS, Baker MK, Chen JC, Wieland RG (1972) Blockade of masculine differentiation in male rat fetuses by maternal injection of antibodies to testosterone-3-bovine serum albumin. Endocrinology 90:716–721

    PubMed  Google Scholar 

  17. Goldstein JL, Wilson JD (1974) Hereditary disorders of sexual development in man. In: Motulsky AG, Lentz W (eds) Birth Defects. Proceedings of the Fourth International Conference, Vienna, Austria. Excerpta Medica, Amsterdam, pp 165–173

    Google Scholar 

  18. Gondos B, Bhiraleus P, Habel CJ (1971) Ultrastructural observations on germ cells in human fetal ovaries. Am J Obstet Gynecol 110:644–652

    PubMed  Google Scholar 

  19. Griffin JE (1979) Testicular feminization associated with a thermolabile androgen receptor in cultured human fibroblasts. J Clin Invest 64:1624–1631

    PubMed  Google Scholar 

  20. Hauser GA (1961) Testikuläre Feminisierung. In: C. Overzier, ed. Die Intersexualität. Thieme, Stuttgart, pp 261–282

    Google Scholar 

  21. Higgins SJ, Gehring U (1978) Molecular mechanism of steroid hormone action. Adv Cancer Res 28:313–397

    PubMed  Google Scholar 

  22. Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE (1974) Steroid 5α-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 186:1213–1215

    PubMed  Google Scholar 

  23. Josso N, Picard JY, Tran D (1977) The antimüllerian hormone. Recent Progr Horm Res 33:117–160

    Google Scholar 

  24. Jost A (1953) Problems of fetal endocrinology: the gonadal and hypophyseal hormones. Recent Progr Horm Res 8:379–418

    Google Scholar 

  25. Jost A (1971) Embryonic sexual differentiation (morphology, physiology, abnormalities). In: Jones HW, Jr., Scott WW (eds) Hermaphroditism, genital anomalies and related endocrine disorders, 2nd rev ed. Williams and Wilkins, Baltimore, pp 16–34

    Google Scholar 

  26. Jost A (1972) A new look at the mechanisms controlling sex differentiation in mammals. John Hopkins Med J 130:38–53

    Google Scholar 

  27. Keenan BS, Meyer WJ, III, Hadjian AJ, Jones HW, Migeon CJ (1974) Syndrome of androgen insensitivity in man: absence of 5α-dihydrotestosterone binding protein in skin fibroblasts. J Clin Endocrinol Metab 38:1143–1146

    PubMed  Google Scholar 

  28. Leshin M, Griffin JE, Wilson JD (1978) Hereditary male pseudohermaphroditism associated with an unstable form of 5α-reductase. J Clin Invest 62:685–691

    PubMed  Google Scholar 

  29. Lubs HA, Jr, Vilar O, Bergenstal DM (1959) Familial male pseudohermaphroditism with labial testes and partial feminization: endocrine studies and genetic aspects. J Clin Endocrinol Metab 19:1110–1129

    PubMed  Google Scholar 

  30. MacDonald PC, Rombaut RP, Siiteri PK (1967) Plasma precursors of estrogen. I. Extent of conversion of plasma Δ4-androstenedione to estrone in normal males and nonpregnant normal, castrate and adrenalectomized females. J Clin Endocrinol Metab 27:1103–1111

    PubMed  Google Scholar 

  31. MacDonald PC, Madden JD, Brenner PF, Wilson JD, Siiteri PK (1979) Origin of estrogen in normal men and in women with testicular feminization. J Clin Endocrinol Metab 49:905–916

    PubMed  Google Scholar 

  32. Meyer WJ, III, Migeon BR, Migeon CJ (1975) Locus on human X chromosome of dihydrotestosterone receptor and androgen insensitivity. Proc Natl Acad Sci 72:1469–1472

    PubMed  Google Scholar 

  33. Milewich L, George FW, Wilson JD (1977) Estrogen formation by the ovary of the rabbit embryo. Endocrinology 100:187–197

    PubMed  Google Scholar 

  34. Morris JM (1953) The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynecol 65:1192–1211

    PubMed  Google Scholar 

  35. Naftolin F, Ryan KJ, Petro Z (1971) Aromatization of androstenedione by the diencephalon. J Clin Endocrinol Metab 33:368–370

    PubMed  Google Scholar 

  36. Neumann F, Steinbeck H, Elger W (1970) Sexualdifferenzierung. Symp Dtsch Ges Endokrin 16:58–82

    Google Scholar 

  37. Neumann F, von Berswordt-Wallrabe R, Elger W, Steinbeck H, Hahn JD, Kramer M (1970) Aspects of androgen-dependent events as studied by antiandrogens. Recent Progr Horm Res 26:337–410

    PubMed  Google Scholar 

  38. Neumann F, Gräf KJ, Elger W (1974) Hormone-induced disturbances in sexual differentiation. In: Raspé G (ed) Advances in the biosciences. No. 13. Hormones and embryonic development. Pergamon Press, Oxford New York Toronto Sydney, pp 71–101

    Google Scholar 

  39. Neumann F, Steinbeck H (1974) Antiandrogens. In: Eichler D, Farah A, Herken H, Welch AD (eds) Handbook of Experimental Pharmacology, vol. XXXV/2, Springer, Berlin Heidelberg New York, pp 235–484

    Google Scholar 

  40. Nowakowski H, Lenz W (1961) Genetic aspects in male hypogonadism. Recent Prog Res Horm Res 17:53–95

    Google Scholar 

  41. Ohno S, Christian LC, Wachtel SS, Koo GC (1976) Hormone-like role of H-Y antigen in bovine freemartin gonad. Nature 261:597–599

    PubMed  Google Scholar 

  42. Ohno S (1979) Major sex determining genes. In: Gross F, Labhart A, Lipsett MB, Mann T, Samuels LT, Zander J (eds) Monographs of Endocrinology, vol. 11. Springer, Berlin Heidelberg New York, p 140

    Google Scholar 

  43. Peters H (1970) Migration of gonocytes into the mammalian gonad and their differentiation. Phil Trans Roy Soc London Ser B 259:91–101

    Google Scholar 

  44. Picard JY, Tran D, Josso N (1978) Biosynthesis of labelled antimüllerian hormone by fetal testes: Evidence of glycoprotein nature of the hormone and for its disulfide bonded structure. Mol Cell Endocrinol 12:17–30

    PubMed  Google Scholar 

  45. Prader A, Siebenmann RE (1957) Nebenniereninsuffizienz bei kongenitaler Lipoidhyperplasie der Nebennieren. Helv paediat Acta 12:569–595

    PubMed  Google Scholar 

  46. Prader A, Zachmann M (1978) Das adrenogenitale Syndrom. In: Labhart A (Hrsg) Klinik der inneren Sekretion, 3. Auflage, Springer, Berlin, S 363–382

    Google Scholar 

  47. Reifenstein EC, Jr (1947) Hereditary familial hypogonadism. Proc Am Fed Clin Res 3:86

    Google Scholar 

  48. Rosenfield RL, Lawrence AM, Liao S, Landau RL (1971) Androgens and androgen responsiveness in the feminizing testis syndrome: comparison of complete and “incomplete” forms. J Clin Endocrinol Metab 32:625–632

    PubMed  Google Scholar 

  49. Rosewater S, Swinup G, Hamwi GJ (1965) Familial gynecomastia. Ann Intern Med 63:377–385

    PubMed  Google Scholar 

  50. Saez JM, De Peretti EM, Morera AM, David M, Bertrand J (1971) Familial male pseudohermaphroditism with gynecomastia due to a testicular 17-ketosteroid reductase defect. I. Studies in vivo. J Clin Endocrinol Metab 32:604–610

    PubMed  Google Scholar 

  51. Schindler AE, Ebert A, Friedrich E (1972) Conversion of androstenedione to estrone by human fat tissue. J Clin Endocrinol Metab 35:627–630

    PubMed  Google Scholar 

  52. Schultz FM, Wilson JD (1974) Virilization of the Wolffian duct in the rat fetus by various androgens. Endocrinology 94:979–986

    PubMed  Google Scholar 

  53. Schweikert HU, Milewich L, Wilson JD (1975) Aromatization of androstenedione by isolated human hairs. J Clin Endocrinol Metab 40:413–417

    PubMed  Google Scholar 

  54. Schweikert HU, Milewich L, Wilson JD (1976) Aromatization of androstenedione by cultured human fibroblasts. J Clin Endocrinol Metab 43:785–795

    PubMed  Google Scholar 

  55. Siiteri PK, MacDonald PC (1973) Role of extraglandular estrogen in human endocrinology. In: Greep RO, Astwood EB (eds) Handbook of Physiology. Section 7, Endocrinology, Vol. II. Female reproductive system. Part I. Am Physiol Soc, Washington, pp 615–629

    Google Scholar 

  56. Siiteri PK, Wilson JD (1974) Testosterone formation and metabolism during male sexual differentiation in the human embryo. J Clin Endocrinol Metab 38:113–125

    PubMed  Google Scholar 

  57. Simpson JL, New M, Peterson RE, German J (1971) Pseudovaginal perineoscrotal hypospadias (PPSH) in sibs. In: Bergsma (ed) Birth Defects: Original Articles Series. Vol. 7. William and Wilkins, Baltimore, pp 140–144

    Google Scholar 

  58. Sloan WR, Walsh PC (1976) Familial persistent müllerian duct syndrome. J Urol 115:459–461

    PubMed  Google Scholar 

  59. Wachtel SS (1977) H-Y antigen: Genetics and serology. Immunol Rev 33:33–58

    PubMed  Google Scholar 

  60. Walsh PC, Madden JD, Harrod MJ, Goldstein JL, MacDonald PC, Wilson JD (1974) Familial incomplete male pseudohermaphroditism, type 2.: decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med 291:944–949

    PubMed  Google Scholar 

  61. Weinstein RL, Kelch RP, Jenner MR, Kaplan SL, Grumbach MM (1974) Secretion of unconjugated androgens and estrogens by the normal and abnormal human testis before and after human chorionic gonadotropin. J Clin Invest 53:1–6

    PubMed  Google Scholar 

  62. Weißbach L, Leyendecker G, Stangenberg Ch, Schweikert HU (1978) Partial insensitivity of hypothalamic-pituitary centers to sexual steroids in the Reifenstein-syndrome. Acta endocr (Kbh) Suppl 215:97

    Google Scholar 

  63. Williams-Ashman HG (1975) Metabolic effects of testicular androgens. In: Hamilton DW, Greep RO (eds) Handbook of Physiology, Section 7: Endocrinology vol. V. Male reproductive system. Am Physiol Soc, Washington, pp 473–490

    Google Scholar 

  64. Wilson JD, Harrod MJ, Goldstein JL, Hemsell DL, MacDonald PC (1974) Familial incomplete male pseudohermaphroditism, type 1: evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome. N Engl J Med. 290:1097–1103

    PubMed  Google Scholar 

  65. Wilson JD (1975) Metabolism of testicular androgens. In: Hamilton DW, Greep RO (eds) Handbook of Physiology. Section 7: Endocrinology, vol. V. Male reproductive system, Am Physiol Soc, Washington, pp 491–508

    Google Scholar 

  66. Witschi E (1948) Migration of the germ cells of human embryos from the yolk sac to the primitive gonadal folds. Carnegie Contrib Embryol No. 209, 32:69–80

    Google Scholar 

  67. Zachmann M, Völlmin JA, Hamilton W, Prader A (1972) Steroid 17,20 desmolase deficiency: a new cause of male pseudohermaphroditism Clin. Endocrinol 1:369–385

    Google Scholar 

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  1. Medizinische Universitäts-Poliklinik Bonn und Department Endokrinpharmakologie, Schering A.G., Berlin

    H. -U. Schweikert & F. Neumann

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Die eigenen Untersuchungen wurden durch die Deutsche Forschungsgemeinschaft Schw 168/5–7 unterstützt

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Schweikert, H.U., Neumann, F. Hormonelle Grundlagen der normalen und pathologischen somatischen Sexualentwicklung. Klin Wochenschr 64, 49–62 (1986). https://doi.org/10.1007/BF01784130

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