Ibuprofen inhibits key genes involved in androgen production in theca-interstitial cells.

OBJECTIVE

To study the effects of ibuprofen on androgen production, gene expression, and cell viability in rat theca-interstitial cells exposed to the proinflammatory stimuli interleukin-1 (IL-1) and lipopolysaccharide (LPS).

DESIGN

Animal study.

SETTING

University-based research laboratory.

PATIENTS/ANIMALS: Theca-interstitial cells were isolated from 30 day old female Sprague Dawley rats.

INTERVENTIONS

Theca cells were cultured with pro-inflammatory media containing IL-1 and LPS and compared with cells cultured in control media.

MAIN OUTCOME MEASURES

Androstenedione quantification was performed on conditioned cell culture medium using liquid chromatography-mass spectrometry. Theca cell viability was assessed using PrestoBlue cell viability assay. The gene expression of , , and was analyzed using quantitative polymerase chain reaction.

RESULTS

Both proinflammatory stimuli IL-1 and LPS increased androstenedione concentration in cell culture medium, and these effects were mitigated with ibuprofen. Both inflammatory agents in addition increased the expression of key genes involved in androgen synthesis: , , and ; the addition of ibuprofen to the culture medium inhibited these effects. Theca cell viability increased with IL-1 and LPS. Ibuprofen inhibited the IL-1-mediated increase in cell viability but did not reverse the effects of LPS.

CONCLUSIONS

In conclusion, our findings support the hypothesis that many of the alterations induced by inflammatory stimuli in theca-interstitial cells are abrogated by the addition of ibuprofen.