INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

Testosterone, not 5α-dihydrotestosterone, stimulates LRH-1 leading to FSH-independent expression of Cyp19 and P450scc in granulosa cells

Show full item record

Bookmark or cite this item: http://hdl.handle.net/10027/8283

Files in this item

File Description Format
PDF 656.full.pdf (2MB) (no description provided) PDF
Title: Testosterone, not 5α-dihydrotestosterone, stimulates LRH-1 leading to FSH-independent expression of Cyp19 and P450scc in granulosa cells
Author(s): Wu, Yan-Guang; Bennett, Jill; Talla, Deepika; Stocco, Carlos
Abstract: Androgens are crucial for normal folliculogenesis and female fertility as evidenced in androgen receptor-null and granulosa cell conditional knockout mice. It is thought, however, that the multiple effects of androgens in the ovary are mainly complementary to the actions of gonadotropins. Using primary rat granulosa cells, we demonstrated that in the absence of gonadotropins, testosterone (T) increases aromatase (Cyp19) and P450 side-change cleavage expression, two enzymes crucial for normal ovarian function. T can be converted into estradiol, a classical estrogen, by Cyp19 and into 5α-dihydrotestosterone, a pure androgen, by 5α-reductase. However, inhibition of Cyp19 and/or 5α-reductase did not prevent the stimulatory effects of T. In contrast, the effect of this steroid was potentiated by blocking 5α-reductase. Additionally, T, not 5α-dihydrotestosterone, stimulates liver receptor homolog-1 (LRH-1) expression, whereas the expression of steroidogenic factor-1 (SF-1) was not affected by either steroid. LRH-1 and SF-1 are transcription factors known to be involved in the regulation of Cyp19. Accordingly, small interference RNA against LRH-1 prevented Cyp19 and P450 side-change cleavage up-regulation whereas anti-SF-1 small interference RNA had no effects. Chromatin immunoprecipitation demonstrated that T stimulation of LRH-1 leads to the recruitment of LRH-1 to the native Cyp19 promoter, which was not affected by cotreatment with 5α-reductase and Cyp19 inhibitors. Finally, gel shift and supershift analysis demonstrated that the androgen receptor binds to an androgen response element located within the LRH-1 promoter. These results provide novel evidence that T has a direct effect on the expression of genes involved in granulosa cell differentiation.
Issue Date: 2011-04
Publisher: The Endocrine Society
Citation Info: Wu, Y. G., Bennett, J., Talla, D., & Stocco, C. 2011. Testosterone, not 5{alpha}-Dihydrotestosterone, Stimulates LRH-1 Leading to FSH-Independent Expression of Cyp19 and P450scc in Granulosa Cells. Mol.Endocrinol. April 2011, 25(4):656–668. doi: 10.1210/me.2010-0367
Type: Article
Description: © 2011 by The Endocrine Society, Molecular Endocrinology
URI: http://hdl.handle.net/10027/8283
ISSN: 0888-8809
Date Available in INDIGO: 2012-04-29
 

This item appears in the following Collection(s)

Show full item record

Statistics

Country Code Views
United States of America 154
China 30
United Kingdom 9
Netherlands 2
Taiwan 2

Browse

My Account

Information

Access Key