A Δ⁴-3-Keto Pathway for Testosterone Synthesis in the Human Spermatozoa

Abstract

The ability of human spermatozoa to metabolize pregnenolone to progesterone and progesterone to testosterone was assessed. Sonicated specimens of freshly ejaculated sperm from two groups of husbands (n= 6, age 32–38 years; n= 6, age 30–51 years) of infertile couples in the range of sperm concentration between 237.5 and 568.5, 100.1 and 248.8 millions per ejaculate, were separately incubated with [7n-³H]pregnenolone and [1,2,6,7,16,17-³H]progesterone. Using the classical reverse-isotope dilution technique the desired products [³H]progesterone and [³]testosterone formed from the respective substrates were isolated and characterized, yielding 1.4 to 12.2% and 3.1 × 10⁻²to 2.0 × 10¹%. Such metabolites were not evident in the controls. The results indicate that the human spermatozoa contain the enzymes necessary for the transformation of pregnenolone to testosterone via the Δ⁴-3-keto route.

Key Words:

• 17α-hydroxylase
• 3β-hydroxysteroid dehydrogenase-5
• 17β-hydroxysteroid oxidoreductase
• 4-ene isomerase
• 20-lyase
• male infertility
• progesterone
• pregnenolone
• spermatozoa
• steroid C-17
• testosterone synthesis