Some investigators have suggested that "dysregulation" of
cytochrome P450c17 alpha may result in the exaggerated secretion of ovarian
androgens in
hyperandrogenism. Although the majority of hyperandrogenic (HA) patients demonstrate an ovarian source for their
androgens, approximately 50% also display adrenocortical hyperactivity and adrenal
androgen excess. To determine whether 17-hydroxylase (17-OH) and/or
17,20-lyase dysregulation is responsible for the adrenocortical abnormalities noted in many HA patients, we studied 92 consecutive women with
hirsutism and/or HA
oligomenorrhea; 26 healthy eumenorrheic nonhirsute women served as controls. The basal levels of total and free
testosterone (T),
sex hormone-binding globulin, and
dehydroepiandrosterone sulfate were measured, and
pregnenolone,
17-hydroxypregnenolone,
progesterone,
17-hydroxyprogesterone,
dehydroepiandrosterone, and
androstenedione were measured 0 and 60 min after the acute iv administration of ACTH-(1-24). Controls and HA patients did not differ in mean age or body mass, but HA women had higher basal T, free T,
dehydroepiandrosterone sulfate,
androstenedione, and LH/FSH and lower
sex hormone-binding globulin levels. The mean estimated basal 17-OH activity was higher among HA patients than in controls. Although 52 HA patients demonstrated solely an exaggerated basal delta 5-17-OH activity estimate, few HA patients had an exaggerated estimate for either basal delta 4-17-OH or
ACTH-stimulated 17-OH activity. No HA patient demonstrated an exaggerated
17,20-lyase basal activity, whereas 14 demonstrated an exaggerated delta 4-17,20-lyase
ACTH-stimulated activity only. There was no association between these estimates of 17-OH and
17,20-lyase activities and the circulating adrenal
androgen levels in HA women. Importantly, none of the patients demonstrated an increase in the basal activities of both 17-OH and
17,20-lyase, and only 4 patients demonstrated an exaggerated
ACTH-stimulated activity of both 17-OH and
17,20-lyase. In conclusion, the steroidogenic profile observed in this population of HA women before and after ACTH-(1-24) stimulation is not consistent with dysregulation of
cytochrome P450c17 alpha and probably represents a generalized alteration of adrenocortical control or biosynthesis.