Dysregulation of cytochrome P450c17α as the cause of polycystic ovarian syndrome

R. L. Rosenfield; R. B. Barnes; J. F. Cara; A. W. Lucky

doi:10.1016/s0015-0282(16)53510-9

Dysregulation of cytochrome P450c17α as the cause of polycystic ovarian syndrome

R. L. Rosenfield^*, R. B. Barnes, J. F. Cara, A. W. Lucky

^*Corresponding author for this work

Obstetrics and Gynecology

Research output: Contribution to journal › Review article › peer-review

282 Scopus citations

Abstract

Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen-forming enzyme (cytochrome P450c17α) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17α.

Original language	English (US)
Pages (from-to)	785-791
Number of pages	7
Journal	Fertility and Sterility
Volume	53
Issue number	5
DOIs	https://doi.org/10.1016/s0015-0282(16)53510-9
State	Published - 1990

Funding

Received November 14, 1989; revised and accepted January 15, 1990. * Supported in part by grants HD-06308 and Rr-00055 from the United States Public Health Service, Bethesda, Maryland. t The Departments of Pediatrics and Medicine, The University of Chicago Pritzker School of Medicine. :j: Reprint requests: Robert L. Rosehfield, M.D., Wyler Children's Hospital, Section of Pediatric Endocrinology, 5841 S. Maryland Avenue (Box 118), Chicago, Illinois 60637. §Department of Obstetrics and Gynecology, The University of Chicago Pritzker School of Medicine. II The Department of Pediatrics, The University of Chicago Pritzker School of Medicine. 1l The Departments of Dermatology and Pediatrics, The University of Cincinnati.

ASJC Scopus subject areas

Obstetrics and Gynecology
Reproductive Medicine

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10.1016/s0015-0282(16)53510-9

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title = "Dysregulation of cytochrome P450c17α as the cause of polycystic ovarian syndrome",

abstract = "Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen-forming enzyme (cytochrome P450c17α) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17α.",

author = "Rosenfield, {R. L.} and Barnes, {R. B.} and Cara, {J. F.} and Lucky, {A. W.}",

note = "Funding Information: Received November 14, 1989; revised and accepted January 15, 1990. * Supported in part by grants HD-06308 and Rr-00055 from the United States Public Health Service, Bethesda, Maryland. t The Departments of Pediatrics and Medicine, The University of Chicago Pritzker School of Medicine. :j: Reprint requests: Robert L. Rosehfield, M.D., Wyler Children's Hospital, Section of Pediatric Endocrinology, 5841 S. Maryland Avenue (Box 118), Chicago, Illinois 60637. §Department of Obstetrics and Gynecology, The University of Chicago Pritzker School of Medicine. II The Department of Pediatrics, The University of Chicago Pritzker School of Medicine. 1l The Departments of Dermatology and Pediatrics, The University of Cincinnati.",

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AU - Rosenfield, R. L.

AU - Barnes, R. B.

AU - Cara, J. F.

AU - Lucky, A. W.

N1 - Funding Information: Received November 14, 1989; revised and accepted January 15, 1990. * Supported in part by grants HD-06308 and Rr-00055 from the United States Public Health Service, Bethesda, Maryland. t The Departments of Pediatrics and Medicine, The University of Chicago Pritzker School of Medicine. :j: Reprint requests: Robert L. Rosehfield, M.D., Wyler Children's Hospital, Section of Pediatric Endocrinology, 5841 S. Maryland Avenue (Box 118), Chicago, Illinois 60637. §Department of Obstetrics and Gynecology, The University of Chicago Pritzker School of Medicine. II The Department of Pediatrics, The University of Chicago Pritzker School of Medicine. 1l The Departments of Dermatology and Pediatrics, The University of Cincinnati.

PY - 1990

Y1 - 1990

N2 - Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen-forming enzyme (cytochrome P450c17α) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17α.

AB - Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen-forming enzyme (cytochrome P450c17α) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17α.

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Dysregulation of cytochrome P450c17α as the cause of polycystic ovarian syndrome

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