The biochemical basis for increased Testosterone production in theca cells propagated from patients with polycystic ovary syndrome

V. L. Nelson, K. N. Qin, R. L. Rosenfield, J. R. Wood, T. M. Penning, R. S. Legro, J. F. Strauss, J. M. McAllister

Research output: Contribution to journalArticle

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Abstract

Ovarian theca cells propagated from patients with polycystic ovary syndrome (PCOS) convert steroid precursors into T more efficiently than normal theca cells. To identify the basis for increased T production by PCOS theca cells, we examined type I-V 17β-hydroxysteroid dehydrogenase (17βHSD) isoform expression in long-term cultures of theca and granulosa cells isolated from normal and PCOS ovaries. RT-PCR analysis demonstrated that theca cells express type V 17βHSD a member of the aldo-keto reductase (AKR) superfamily (17βHSDV, AKR1C3), whereas expression of type I, II, and IV 17βHSD, which are members of the short-chain dehydrogenase/reductase superfamily, was limited to granulosa cells. Type III 17βHSD, the testicular isoform, was not detected in either granulosa or theca cells. Northern and real-time PCR analyses demonstrated that 17βHSDV transcripts were not significantly increased in PCOS theca cells compared with normal theca cells. RT-PCR analysis revealed that theca cells also express another AKR, 20αHSD (AKR1C1). Both basal and forskolin-stimulated 20αHSD mRNA levels were increased in PCOS theca cells compared with normal theca cells. However, 17βHSD enzyme activity per theca cell was not significantly increased in PCOS, suggesting that neither AKR1C3 nor AKR1C1 contributes to the formation of T in this condition. In contrast, 17α-hydroxylase/C17,20 lyase and 3βHSD enzyme activities were elevated in PCOS theca cells, driving increased production of T precursors. These findings indicate that 1) increased T production in PCOS theca cells does not result from dysregulation of "androgenic" 17βHSD activity or altered expression of AKRs that may express 17βHSD activity; and 2) increased synthesis of T precursors is the primary factor driving enhanced T secretion in PCOS.

Original languageEnglish (US)
Pages (from-to)5925-5933
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number12
DOIs
StatePublished - Jan 1 2001

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Theca Cells
Polycystic Ovary Syndrome
Testosterone
Enzyme activity
Granulosa Cells
Oxidoreductases
Protein Isoforms
Lyases
Colforsin
Mixed Function Oxygenases
3(17)-hydroxysteroid dehydrogenase
Steroids
Polymerase Chain Reaction
Messenger RNA
Enzymes

ASJC Scopus subject areas

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

Cite this

The biochemical basis for increased Testosterone production in theca cells propagated from patients with polycystic ovary syndrome. / Nelson, V. L.; Qin, K. N.; Rosenfield, R. L.; Wood, J. R.; Penning, T. M.; Legro, R. S.; Strauss, J. F.; McAllister, J. M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 12, 01.01.2001, p. 5925-5933.

Research output: Contribution to journalArticle

Nelson, V. L. ; Qin, K. N. ; Rosenfield, R. L. ; Wood, J. R. ; Penning, T. M. ; Legro, R. S. ; Strauss, J. F. ; McAllister, J. M. / The biochemical basis for increased Testosterone production in theca cells propagated from patients with polycystic ovary syndrome. In: Journal of Clinical Endocrinology and Metabolism. 2001 ; Vol. 86, No. 12. pp. 5925-5933.
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