[The alternative androgen synthesis pathway in humans]

Area of Science:

• Endocrinology
• Molecular Biology
• Reproductive Health

Background:

• Recent discoveries have revealed novel pathways for androgen synthesis in humans.
• These alternative pathways are distinct from previously understood mechanisms involving classical intermediates.

Purpose of the Study:

• To review and highlight newly discovered androgen synthesis pathways in humans.
• To discuss the implications of these pathways in male sexual differentiation, congenital adrenal hyperplasia, and prostate cancer.

Main Methods:

• A selective literature search was conducted using PubMed.
• The review synthesizes findings from two independent studies published within the last year.

Main Results:

• A new androgen synthesis pathway, initially identified in marsupials, has been confirmed in humans.
• This pathway is crucial for male sexual differentiation and plays a significant role in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
• An alternative pathway bypassing testosterone is implicated in driving castration-resistant prostate cancer.

Conclusions:

• New androgen synthesis pathways are active in humans.
• These pathways are clinically relevant for male sexual development, adrenal disorders, and prostate cancer.
• The clinical significance is often missed as these pathways circumvent classical androgen intermediates like dehydroepiandrosterone, androstenedione, and testosterone.