17 beta-
Hydroxysteroid dehydrogenase (17 beta HSD) deficiency is a rare cause of
male pseudohermaphroditism, but is a frequent disorder among a highly inbred Arab population in the Gaza strip. Affected individuals are born and reared as females until puberty, when marked
virilization occurs, leading in many cases to the spontaneous adoption of a male gender role. To investigate the mechanisms and site(s) of
androgen production, we determined the gonadal and extragonadal
steroid patterns in two postpubertal
male pseudohermaphroditism patients, who were castrated and reared as females. Before
castration, both patients had very high plasma levels of
androstenedione (delta 4-A), normal or moderately low levels of
testosterone (T), and significantly elevated delta 4-A/T ratios (P less than 0.01).
Dihydrotestosterone (DHT) levels were normal or high, while the DHT/T ratios were lower than normal (P less than 0.01), suggesting enhanced
5 alpha-reductase activity. These abnormalities were much more severe in spermatic venous blood. 17 beta HSD deficiency was also found in the delta 5-pathway, by high
dehydroepiandrosterone (
DHEA) levels and very high dehydroxyepiandrosterone/
delta 5-androstenediol (
DHEA/delta 5-diol) ratios, and in peripheral tissue metabolites, by very high
androsterone glucuronide/3 alpha-androstanediol
glucuronide ratios (P less than 0.01). The
estrogen pathway was also impaired (P less than 0.01), even though both
estrone and
estradiol levels were elevated.
Gonadectomy significantly reduced all
androgens and
estrogens (P less than 0.01), but when compared to 42 castrated controls, both patients had lower delta 4-A and higher T levels. The delta 4-A/T ratio was lower than that in controls, indicating normal to enhanced extragonadal 17 beta HSD activity. A similar pattern was observed in the delta 5- and
estrogen pathways. DHT levels were within normal limits, and 3 alpha-diol was moderately decreased. These data suggest that testicular 17 beta HSD activity is under a different genetic control from that in extragonadal tissues. Affected males lack the testicular
enzyme, but their extragonadal 17 beta HSD activity is normal or enhanced. Together with enhanced
5 alpha-reductase activity, this represents a highly efficient compensatory mechanism for
androgen and
estrogen production after puberty.