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
-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
-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
-hydroxysteroid dehydrogenase (3
-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
-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