Abstract:
:In rat ovary, androgen receptor (AR) is predominantly expressed in granulosa cells and is developmentally regulated. However, the exact mechanism that is responsible for the regulation of AR in granulosa cells has not been elucidated. The aim of this study was to examine 1) the levels of AR messenger RNA (mRNA) expression in granulosa cells from follicles of different size and 2) the effects of FSH, 8-bromo-cAMP, androgen, and estrogen on AR mRNA levels in granulosa cells in vitro. The abundance of AR mRNA was examined by ribonuclease protection assay using 32P-labeled AR complementary RNA probe and related to that of P450aromatase (P450arom) mRNA, a well established maker of granulosa cell differentiation. In large follicles (> 400 microns in diameter), the abundance of AR mRNA was decreased to 51% of that in small follicles (< 200 microns; P < 0.01), whereas the abundance of P450arom mRNA increased to 277% (P < 0.01). In medium follicles (200-400 microns), the abundance of AR mRNA was maintained (101%), whereas the abundance of P450arom mRNA increased to 202% of that in small follicles (P < 0.05). Treatment with FSH (0-300 ng/ml) or 8-bromo-cAMP (0-4 mM) induced P450arom mRNA in the cultured granulosa cells in a dose-dependent manner; however, it did not affect the levels of AR mRNA expression. Treatment with 5 alpha-dihydrotestosterone (1 microM) resulted in a significant reduction in the abundance of AR mRNA to 67% of the control value (P < 0.05). This effect was reversed by the addition of FSH (100 ng/ml; P < 0.01). Treatment with diethylstilbestrol (1 microM), alone or in combination with FSH (100 ng/ml), did not have any significant effect, although these treatments tended to decrease the abundance of AR mRNA to 81% and 85%, respectively. Both 5 alpha-dihydrotestosterone and diethylstilbestrol dramatically enhanced the abundance of FSH-induced P450arom mRNA compared to the effect of FSH alone. These results indicate that 1) the down-regulation of AR mRNA expression takes place in granulosa cells of preovulatory follicles; 2) FSH is not directly responsible for this event; and 3) androgen down-regulates AR mRNA expression in immature granulosa cells, and this effect is reversed by FSH. We conclude that androgen and FSH jointly regulate AR mRNA expression in rat granulosa cells.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Tetsuka M,Hillier SGdoi
10.1210/endo.137.10.8828500subject
Has Abstractpub_date
1996-10-01 00:00:00pages
4392-7issue
10eissn
0013-7227issn
1945-7170journal_volume
137pub_type
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