Der alternative Androgensyntheseweg des Menschen

Zusammenfassung

Hintergrund:

Im letzten Jahr konnten beim Menschen neue alternative Androgensynthesewege nachgewiesen werden, welche zuvor nur bei einigen Nage- und Beuteltieren bekannt waren. Ziel dieses Artikels ist es, die neuen Erkenntnisse um diese neuen Androgensynthesewege beim Menschen darzustellen.

Methodik:

Selektive Literaturrecherche in PubMed.

Ergebnisse:

Nachdem bei einer Känguruhart ein neuer Stoffwechselweg der Androgensyn­these aufgezeigt werden konnte, ist die Bedeutung dieses neuen Androgensyntheseweges im Verlauf des letzten Jahres auch beim Menschen nachgewiesen worden. Zum Einen konnte die Bedeutung des neuen Syntheseweges für die fetale männliche Geschlechtsentwicklung belegt werden. Es wurde nachgewiesen, dass bei Jungen mit Unterentwicklung der äußeren Geschlechtsorgane ein spezielles Gen, welches für ein Enzym des neuen Androgensyntheseweges kodiert, defekt war. Des Weiteren konnte bei Patienten mit Adrenogenitalem Syndrom, welche vermehrt Androgene bilden, gezeigt werden, dass ein Teil der Androgene dem neuen Syntheseweg entstammen. Zudem konnte auch in der Prostata beim kastrations­resistenten Prostatakarzinom ein alternativer Androgensyntheseweg nachgewiesen werden.

Schlussfolgerung:

Durch Änderung des Angebotes an Androgenvorläufern, sowie Änderungen der Aktivität von Enzymen, die an der Androgensynthese beteiligt sind, können neue alternative Synthesewege beim Menschen beschritten werden. Diese spielen sich jedoch durch ein Umgehen der gewöhnlichen Vorläuferandrogene wie Dehydroepiandrosteron, Androstendion und Testosteron im Verborgenen ab.

Abstract

Objective:

During the last year, alternative androgen synthesis pathways have been discovered in humans. This review article highlights these new concepts of androgen synthesis.

Design and Methods:

We performed a selec­tive literature research using PubMed.

Results:

After the discovery of a new androgen synthesis pathway in marsupials, this new path­way of androgen synthesis could be established in humans during the last year from two independent studies. One of them could demonstrate that two pathways of androgen synthesis are needed for male sexual differentiation in humans; the other study established that the new pathway is an important source of androgen synthesis in congenitale adrenal hyperplasia due to 21-hydroxylase deficiency. Additionally, it has been shown that an alternative androgen synthesis pathway that bypasses testosterone drives castration resistant prostate cancer.

Conclusion:

New and alternative androgen path­ways occur in humans. Importantly, these path­ways remain cryptic for the clinician, because the androgen synthesis circumvents classical in­termediates like dehydroepiandrosterone, androstenedione and testosterone.

Schlüssenwörter

alternative Androgensynthese - Backdoor Pathway - Dihydrotestosteron - Adrenogenitales Syndrom - 17α-Hydroxyallo­pregnanolon

Key words

alternative androgen synthesis pathway - backdoor pathway - dihydrotestosterone - congential adrenal hyperplasia - 17α-hydroxyallo­pregnanolone

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