Adrenal androgen excess in women: Lack of a role for 17-hydroxylase and 17,20-lyase dysregulation

Ricardo Azziz, Edwin L. Bradley, H. Downing Potter, Larry R. Boots

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Some investigators have suggested that "dysregulation" of cytochrome P450c17α 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, - 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 Δ5-17-OH activity estimate, few HA patients had an exaggerated estimate for either basal Δ4-17-OH or ACTH-stimulated 17-OH activity. No HA patient demonstrated an exaggerated 17,20-lyase basal activity, whereas 14 demonstrated an exaggerated Δ4-17,20-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 P450c17α and probably represents a generalized alteration of adrenocortical control or biosynthesis.

Original languageEnglish (US)
Pages (from-to)400-405
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number2
DOIs
StatePublished - Jan 1 1995

Fingerprint

Steroid 17-alpha-Hydroxylase
Mixed Function Oxygenases
Androgens
Adrenocorticotropic Hormone
Cosyntropin
Sex Hormone-Binding Globulin
Dehydroepiandrosterone Sulfate
Androstenedione
Cytochromes
17-alpha-Hydroxypregnenolone
17-alpha-Hydroxyprogesterone
Pregnenolone
Dehydroepiandrosterone
Biosynthesis
Oligomenorrhea
Progesterone
Hyperandrogenism
Testosterone
Hirsutism
Association reactions

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Adrenal androgen excess in women : Lack of a role for 17-hydroxylase and 17,20-lyase dysregulation. / Azziz, Ricardo; Bradley, Edwin L.; Potter, H. Downing; Boots, Larry R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 2, 01.01.1995, p. 400-405.

Research output: Contribution to journalArticle

Azziz, Ricardo ; Bradley, Edwin L. ; Potter, H. Downing ; Boots, Larry R. / Adrenal androgen excess in women : Lack of a role for 17-hydroxylase and 17,20-lyase dysregulation. In: Journal of Clinical Endocrinology and Metabolism. 1995 ; Vol. 80, No. 2. pp. 400-405.
@article{d6be748dc9904f09a3c6f0790fcc844f,
title = "Adrenal androgen excess in women: Lack of a role for 17-hydroxylase and 17,20-lyase dysregulation",
abstract = "Some investigators have suggested that {"}dysregulation{"} of cytochrome P450c17α 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, - 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 Δ5-17-OH activity estimate, few HA patients had an exaggerated estimate for either basal Δ4-17-OH or ACTH-stimulated 17-OH activity. No HA patient demonstrated an exaggerated 17,20-lyase basal activity, whereas 14 demonstrated an exaggerated Δ4-17,20-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 P450c17α and probably represents a generalized alteration of adrenocortical control or biosynthesis.",
author = "Ricardo Azziz and Bradley, {Edwin L.} and Potter, {H. Downing} and Boots, {Larry R.}",
year = "1995",
month = "1",
day = "1",
doi = "10.1210/jcem.80.2.7852496",
language = "English (US)",
volume = "80",
pages = "400--405",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "2",

}

TY - JOUR

T1 - Adrenal androgen excess in women

T2 - Lack of a role for 17-hydroxylase and 17,20-lyase dysregulation

AU - Azziz, Ricardo

AU - Bradley, Edwin L.

AU - Potter, H. Downing

AU - Boots, Larry R.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Some investigators have suggested that "dysregulation" of cytochrome P450c17α 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, - 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 Δ5-17-OH activity estimate, few HA patients had an exaggerated estimate for either basal Δ4-17-OH or ACTH-stimulated 17-OH activity. No HA patient demonstrated an exaggerated 17,20-lyase basal activity, whereas 14 demonstrated an exaggerated Δ4-17,20-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 P450c17α and probably represents a generalized alteration of adrenocortical control or biosynthesis.

AB - Some investigators have suggested that "dysregulation" of cytochrome P450c17α 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, - 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 Δ5-17-OH activity estimate, few HA patients had an exaggerated estimate for either basal Δ4-17-OH or ACTH-stimulated 17-OH activity. No HA patient demonstrated an exaggerated 17,20-lyase basal activity, whereas 14 demonstrated an exaggerated Δ4-17,20-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 P450c17α and probably represents a generalized alteration of adrenocortical control or biosynthesis.

UR - http://www.scopus.com/inward/record.url?scp=0028852634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028852634&partnerID=8YFLogxK

U2 - 10.1210/jcem.80.2.7852496

DO - 10.1210/jcem.80.2.7852496

M3 - Article

C2 - 7852496

AN - SCOPUS:0028852634

VL - 80

SP - 400

EP - 405

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -