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BOR - Papers in Press, published online ahead of print January 7, 2004.
Biol Reprod 2004, 10.1095/biolreprod.103.022855
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Submitted September 3, 2003
Returned for revision October 3, 2003
Accepted December 30, 2003

Mechanisms of Hormone Action


Upregulation of Steroidogenic Enzymes and Ovarian 17{beta}-Estradiol in Human Granulosa-Lutein Cells by Cordyceps sinensis Mycelium

Bu-Miin Huang , Kuei-Yang Hsiao , Pei-Chin Chuang , Meng-Hsing Wu , Hsien-An Pan , and Shaw-Jenq Tsai *

* To whom correspondence should be addressed. E-mail: seantsai{at}mail.ncku.edu.tw.

Abstract
There is increasing evidence that 17{beta}-estradiol (E2) directly influences the quality of maturing oocytes and thus the outcome of assisted reproduction treatment. Although Cordyceps sinensis (CS) mycelium, a Chinese herbal medicine, is believed to enhance libido and fertility in both sexes, the mechanism of its effect in women has not been determined. The aim of the present study was to evaluate the effects of CS on steroidogenic enzyme expression and E2 biosynthesis in human granulosa-lutein cells (GLC). We found that CS induced E2 production by GLC in a dose- and time-dependent manner and that 3 h treatment with CS induced increased levels of mRNAs coding for the P450 side chain cleavage enzyme (P450scc), 3{beta}-hydroxysteroid dehydrogenase (3{beta}-HSD), and aromatase. Western blot analysis demonstrated that, after treatment with CS for 3 h, protein levels of steroidogenic acute regulatory protein (StAR) and aromatase were upregulated while P450scc and 3{beta}-HSD levels showed no substantial change. New protein synthesis was required for CS-induced E2 production, since it was abrogated by cycloheximide pretreatment. Addition of 22(R)-hydroxycholesterol, thus bypassing the need for StAR protein, did not induce as much level E2 production as CS treatment, indicating that upregulation of StAR protein was not the only factor contributing to CS-induced steroidogenesis. Cotreatment of GLCs with CS and aminoglutethimide, an aromatase inhibitor, completely abolished CS-induced E2 production. In conclusion, treatment of GLCs with CS results in increased E2 production due, at least in part, to increased StAR and aromatase expression. These data may help in the development of treatment regimens to improve the success rate of in vitro fertilization.

Key words: Mechanisms of Hormone Action • Ovary • Estradiol • Granulosa cells • Steroid hormones





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