In vitro effect of dehydroepiandrosterone sulfate on steroid receptors, aromatase, cyclooxygenase-2 expression, and steroid hormone production in preovulatory human granulosa cells

ObjectiveTo examine the effect of a low concentration of DHEAS on the expression of the androgen receptor, estrogen receptor α and β, progesterone receptor, aromatase, 3-β-hydroxysteroid dehydrogenase, and cyclooxygenase-2 in human preovulatory granulosa cells, and to measure their production of steroid hormones (estrone, estradiol, progesterone, androstenedione, and testosterone).DesignAnalysis of cultured primary human preovulatory granulosa cells by real-time reverse-transcriptase polymerase chain reaction and assays of hormone production.SettingOsaka City University Postgraduate School of Medicine.Intervention(s)Preovulatory granulosa cells were collected from follicular fluid obtained from patients undergoing transvaginal oocyte retrieval with ultrasound guidance. The cells were cultured in the absence or presence of a low concentration of DHEAS. Real-time reverse-transcriptase polymerase chain reaction was performed to quantify the RNA expression of the investigated genes, and steroid hormone (estrone, estradiol, progesterone, androstenedione, and testosterone) levels were measured in the culture medium.Main Outcome Measure(s)Changes in [1] the levels of mRNAs encoding androgen receptor, estrogen receptor α, estrogen receptor β, progesterone receptor, aromatase, 3-β-hydroxysteroid dehydrogenase, and cyclooxygenase-2; and [2] the levels of steroid hormones (estrone, estradiol, progesterone, androstenedione, and testosterone) in the culture medium.Result(s)Treatment of granulosa cells with 20 ng/mL DHEAS increased the expression of androgen receptor, aromatase, 3-β-hydroxysteroid dehydrogenase, and cyclooxygenase-2, reduced the expression of estrogen receptor β, and increased estrone and estradiol levels, but had no effect on progesterone, androstenedione, or testosterone levels.Conclusion(s)DHEAS may be an essential trigger of ovulation.