Troglitazone is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase enzyme in the ovary

Slavisa Gasic, Manubi Nagamani, Allan Green, Randall Urban

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

OBJECTIVE: Troglitazone is a potent inhibitor of progesterone release from porcine granulosa cells. This is associated with a marked increase in pregnenolone secretion, implicating inhibition of the 3β-hydroxysteroid dehydrogenase enzyme. This study determined whether troglitazone is a direct inhibitor of 3β-hydroxysteroid dehydrogenase activity. STUDY DESIGN: Homogenates of porcine granulosa cells underwent classic enzyme kinetic analysis through Lineweaver-Burke and Dixon plotting. Human ovarian homogenates were also assayed for the effects of troglitazone on 3β-hydroxysteroid dehydrogenase enzyme activity. Enzyme kinetics data were analyzed by the HyperKinetics software program. Analysis of variance was used to determine statistical significance for human ovarian homogenate experiments. RESULTS: In porcine granulosa cells Lineweaver-Burke analysis found that troglitazone inhibition of 3β-hydroxysteroid dehydrogenase enzyme activity was competitive in nature, with 5 μg/mL troglitazone increasing the apparent Michaelis constant from 1.3 to 4.3 βmol/L (no change in maximum velocity). Dixon plot analysis demonstrated that the inhibition constant for troglitazone of 3β-hydroxysteroid dehydrogenase is approximately 6.5 μg/mL, which is in the same order of magnitude as its therapeutic concentration in blood. Troglitazone also significantly decreased the activity of 3β-hydroxysteroid dehydrogenase in homogenates of human ovarian tissue. CONCLUSION: We conclude that troglitazone can inhibit steroidogenesis in the ovary by direct competitive inhibition of 3β-hydroxysteroid dehydrogenase.

Original languageEnglish (US)
Pages (from-to)575-579
Number of pages5
JournalAmerican Journal of Obstetrics and Gynecology
Volume184
Issue number4
DOIs
StatePublished - 2001

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troglitazone
3-Hydroxysteroid Dehydrogenases
Ovary
Enzymes
Granulosa Cells
Swine
Pregnenolone
Progesterone

Keywords

  • 3β-Hydroxysteroid dehydrogenase
  • Granulosa cells
  • Polycystic ovary syndrome
  • Progesterone
  • Steroidogenesis
  • Troglitazone

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Troglitazone is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase enzyme in the ovary. / Gasic, Slavisa; Nagamani, Manubi; Green, Allan; Urban, Randall.

In: American Journal of Obstetrics and Gynecology, Vol. 184, No. 4, 2001, p. 575-579.

Research output: Contribution to journalArticle

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