Letrozole increases ovarian growth and Cyp17a1 gene expression in the rat ovary

Israel Ortega, Anna Sokalska, Jesus A. Villanueva, Amanda B. Cress, Donna H. Wong, Elisabet Stener-Victorin, Scott D Stanley, Antoni J. Duleba

Research output: Contribution to journalArticle

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Abstract

Objective: To evaluate the effects of letrozole on ovarian size and steroidogenesis in vivo, as well as on proliferation and steroidogenesis of theca-interstitial cells alone and in coculture with granulosa cells using an in vitro model. Design: In vivo and in vitro studies. Setting: Research laboratory. Animal(s): Immature Sprague-Dawley female rats. Intervention(s): In vivo effects of letrozole were studied in intact rats receiving either letrozole (90-day continuous-release SC pellets, 400 μg/d) or placebo pellets (control group). In in vitro experiments, theca cells were cultured alone or in coculture with granulosa cells in the absence or presence of letrozole. Main Outcome Measure(s): Deoxyribonucleic acid synthesis was determined by thymidine incorporation assay; steroidogenesis by mass spectrometry; and steroidogenic enzyme messenger RNA (mRNA) expression by polymerase chain reaction. Result(s): In vivo, letrozole induced an increase in ovarian size compared with the control group and also induced a profound increase of androgen, LH levels, and Cyp17a1 mRNA expression. Conversely, a decrease in Star, Cyp11a1, and Hsd3b1 transcripts was observed in letrozole-exposed rats. In vitro, letrozole did not alter either theca cell proliferation or Cyp17a1 mRNA expression. Similarly, letrozole did not affect Cyp17a1 transcripts in granulosa-theca cocultures. Conclusion(s): These findings suggest that letrozole exerts potent, but indirect, effect on growth of rat ovary and dramatically increases androgen levels and Cyp17a1 mRNA expression, the key enzyme regulating the androgen biosynthesis pathway. The present findings reveal novel mechanisms of action of letrozole in the rat ovary.

Original languageEnglish (US)
Pages (from-to)889-896
Number of pages8
JournalFertility and Sterility
Volume99
Issue number3
DOIs
StatePublished - Mar 1 2013

Fingerprint

letrozole
Ovary
Gene Expression
Growth
Theca Cells
Coculture Techniques
Androgens
Messenger RNA
Granulosa Cells
Control Groups

Keywords

  • CYP17A1
  • letrozole
  • ovarian theca-interstitial cells
  • proliferation
  • steroidogenesis

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Ortega, I., Sokalska, A., Villanueva, J. A., Cress, A. B., Wong, D. H., Stener-Victorin, E., ... Duleba, A. J. (2013). Letrozole increases ovarian growth and Cyp17a1 gene expression in the rat ovary. Fertility and Sterility, 99(3), 889-896. https://doi.org/10.1016/j.fertnstert.2012.11.006

Letrozole increases ovarian growth and Cyp17a1 gene expression in the rat ovary. / Ortega, Israel; Sokalska, Anna; Villanueva, Jesus A.; Cress, Amanda B.; Wong, Donna H.; Stener-Victorin, Elisabet; Stanley, Scott D; Duleba, Antoni J.

In: Fertility and Sterility, Vol. 99, No. 3, 01.03.2013, p. 889-896.

Research output: Contribution to journalArticle

Ortega, I, Sokalska, A, Villanueva, JA, Cress, AB, Wong, DH, Stener-Victorin, E, Stanley, SD & Duleba, AJ 2013, 'Letrozole increases ovarian growth and Cyp17a1 gene expression in the rat ovary', Fertility and Sterility, vol. 99, no. 3, pp. 889-896. https://doi.org/10.1016/j.fertnstert.2012.11.006
Ortega I, Sokalska A, Villanueva JA, Cress AB, Wong DH, Stener-Victorin E et al. Letrozole increases ovarian growth and Cyp17a1 gene expression in the rat ovary. Fertility and Sterility. 2013 Mar 1;99(3):889-896. https://doi.org/10.1016/j.fertnstert.2012.11.006
Ortega, Israel ; Sokalska, Anna ; Villanueva, Jesus A. ; Cress, Amanda B. ; Wong, Donna H. ; Stener-Victorin, Elisabet ; Stanley, Scott D ; Duleba, Antoni J. / Letrozole increases ovarian growth and Cyp17a1 gene expression in the rat ovary. In: Fertility and Sterility. 2013 ; Vol. 99, No. 3. pp. 889-896.
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