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[Androgen insensitivity syndromes]
F Kuttenn1, F Wright, P Spritzer
1Service Endocrinologie et Médecine de la Reproduction, Hôpital Necker, Paris.
Abstract:
The syndromes of androgen resistance illustrate a special field of endocrinology, that is pathology of target-tissues. These syndromes are responsible for male pseudohermaphroditism and provoke in XY subjects, with a normal testicular androgen secretion, abnormalities in the phenotype with all the possibilities from an "idealistically" female phenotype in the testicular feminization syndrome to an almost normal male phenotype in the mildest forms of the incomplete syndrome. Understanding of these syndromes has strongly benefited of progress in biochemistry and molecular biology concerning the mechanism of action of androgens. On the other hand, understanding androgen mechanism expanded markedly from parallel clinical observation and biochemical investigation permitted by methodological progress: plasma hormones assays, 5 alpha-reductase and androgen receptor qualitative and quantitative determinations. The complete form of the testicular feminization syndrome seems to be due--in most cases--to an absence of the androgen receptor whereas the incomplete forms of the syndrome are related either to insufficient amount or qualitative alteration of the receptor or to a defect of 5 alpha-reductase, the key-enzyme which transforms testosterone to its active metabolite dihydrotestosterone in androgen target-cells. In some cases (approximately equal to 10%) the mechanism of androgen insensitivity could not be identified. The abnormality might be downstream the receptor at various possible steps = binding of the complex androgen-receptor to the chromatin, transcription or post-transcription process. These cases can be useful models for understanding the ultimate steps of the androgen mechanism of action.
Insights
Androgen resistance syndromes cause male pseudohermaphroditism by affecting how target tissues respond to androgens. Defects in the androgen receptor or 5 alpha-reductase enzyme explain most cases, impacting male sexual development.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Context:
- Androgen resistance syndromes represent a critical area in endocrinology, focusing on target tissue pathology.
- These conditions lead to male pseudohermaphroditism in XY individuals with normal testicular androgen production.
- Phenotypic variations range from a female appearance in testicular feminization syndrome to near-normal male phenotypes in milder forms.
Purpose:
- To elucidate the mechanisms underlying androgen resistance syndromes.
- To explore the role of androgen receptor and 5 alpha-reductase in male sexual development.
- To investigate unidentified causes of androgen insensitivity downstream of the receptor.
Summary:
- Complete testicular feminization syndrome is often linked to absent androgen receptors.
- Incomplete forms involve altered androgen receptor quantity/quality or 5 alpha-reductase defects.
- Approximately 10% of cases have unidentified defects, potentially involving chromatin binding or transcription processes.
Impact:
- Advances in biochemistry and molecular biology have enhanced understanding of androgen action.
- Methodological progress, including hormone assays and receptor analysis, aids clinical investigation.
- Unexplained cases offer unique models for studying the terminal steps of androgen signaling pathways.