Zusammenfassung
Die Gonaden sind zunächst unabhängig vom chromosomalen Geschlecht als undifferenzierte Primordien angelegt. Die entscheidende Grundlage für die Entwicklung der bipotenten Gonade in Hoden ist die Expression des Y-chromosomalen Gens sry. Dies induziert die Differenzierung von Sertoli-Zellen, die ihrerseits die Entwicklung der Müller-Gänge unterdrücken und die von Leydig-Zellen fördern. Zudem induzieren sie eine Kaskade der die Hodenentwicklung unterstützenden Transkriptionsfaktoren. Entwicklungsstörungen der Hoden gehen meist mit einer mangelnden Virilisierung von Feten mit männlichem Karyotyp einher. Molekulare Ursachen können Mutationen der Gene für WT-1, SF-1, DAX-1, SOX-9, INSL-3 oder den LH-Rezeptor sein. insl-3-Mutationen sind für die häufigste Störung der Hodenentwicklung, den Maldeszensus, verantwortlich. Die von den primären Entwicklungsdefekten des Hodens abzugrenzenden Störungen der Androgensynthese und Androgenrezeptordefekte stellen die häufigste Ursache eines Pseudohermaphroditismus masculinus dar. Die Defekte der Hodenentwicklung beruhen häufig auf heterozygoten Funktionsverlustmutationen.
Abstract
The gonadal anlagen are initially undifferentiated primordia that are not dependent on the chromosomal gender. The decisive basis for development of the bipotent gonads in the testes is the expression of the Y-chromosome sry gene. This induces the differentiation of Sertoli cells, which suppress the development of the muellerian ducts and foster that of Leydig cells. In addition, they induce a cascade of transcription factors supporting development of the testes. Developmental impairment of the testes are generally associated with inadequate virilization of fetuses with a male karyotype. Possible molecular causes are mutations of the genes for WT-1, SF-1, DAX-1, SOX-9, Insl-3 or the LH receptor. Mutations of Insl-3 are responsible for the most frequent impairment of testicular development, undescended testes. Disturbances of androgen synthesis and defective androgen receptors, which must be differentiated from primary developmental defects affecting the testes, are the most frequent cause of male pseudohermaphroditism. In the case of defects of testicular development there are often underlying heterozygotic function loss mutations.
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Literatur
Bruening W, Bardeesy N, Silverman BL et al. (1992) Germline intronic and exonic mutations in the Wilms’ tumour gene (WT1) affecting urogenital development. Nat Genet 1:144–148
Pelletier J, Bruening W, Kashtan CE et al. (1991) Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67:437–447
Achermann JC, Ito M, Hindmarsh PC et al. (1999) A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. Nat Genet 22:125–126
Achermann JC, Ozisik G, Ito M et al. (2002) Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner. J Clin Endocrinol Metab 87:1829–1833
Koopman P, Gubbay J, Vivian N et al. (1991) Male development of chromosomally female mice transgenic for sry. Nature 351:117–121
Morais da Silva S, Hacker A, Harley V et al. (1996) sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds. Nat Genet 14:62–68
Achermann JC, Silverman BL, Habiby RL et al. (2000) Presymptomatic diagnosis of X-linked adrenal hypoplasia congenita by analysis of DAX1. J Pediatr 137:878–881
Peter M, Viemann M, Partsch C-J et al. (1998) Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the dax-1 gene. J Clin Endocrinol Metab 83:2666–2674
Canto P, Escudero I, Soderlund D et al. (2003) A novel mutation of the insulin-like 3 gene in patients with cryptorchidism. J Hum Genet 48:86–90
Kumagai J, Hsu SY, Matsumi H et al. (2002) INSL3/leydig insulin-like peptide activates the LGR8 receptor important in testis descent. J Biol Chem 277:31283–31286
Barbosa AS, Hadjiathanasiou CG, Theodoridis C et al. (1999) The same mutation affecting the splicing of wt1 gene is present on Frasier syndrome patients with or without Wilms’ tumor. Hum Mutat 13:146–153
Little M, Wells C (1997) A clinical overview of wt1 gene mutations. Hum Mutat 9:209–225
Correa V, Domenice S, Berenice B (2004) Mendonca. J Clin Endocrinol Metab 89:1767–1772
Wagner T, Wirth J, Meyer J et al. (1994) Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene sox9. Cell 79:1111–1120
Kremer H, Kraaij R, Toledo SPA et al. (1995) Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet 9:160–164
Wu S-M, Hallermeier KM, Laue L et al. (1998) Inactivation of the luteinizing hormone/chorionic gonadotropin receptor by an insertional mutation in Leydig cell hypoplasia. Mol Endocrinol 12:1651–1660
Gromoll J, Eiholzer U, Nieschlag E et al. (2000) Male hypogonadism caused by homozygous deletion of exon 10 of the luteinizing hormone (LH) receptor: differential action of human chorionic gonadotropin and LH. J Clin Endocrinol Metab 85:2281–2286
Morel Y, Rey R, Teinturier C et al. (2002) Aetiological diagnosis of male sex ambiguity: a collaborative study. Eur J Pediatr 161:49–59
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Grüters, A. Entwicklung und Entwicklungsstörungen der Hoden. Monatsschr Kinderheilkd 153, 424–429 (2005). https://doi.org/10.1007/s00112-005-1132-3
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DOI: https://doi.org/10.1007/s00112-005-1132-3