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

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267 Scopus citations


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
Issue number12
Publication statusPublished - Jan 1 2001


ASJC Scopus subject areas

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

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