help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chiang, C.-H.
Right arrow Articles by Leung, P. C. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chiang, C.-H.
Right arrow Articles by Leung, P. C. K.
The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 10 3828-3839
Copyright © 2000 by The Endocrine Society

Original Studies

Hormonal Regulation of Estrogen Receptor {alpha} and ß Gene Expression in Human Granulosa-Luteal Cells in Vitro1

Chi-Hsin Chiang2, Kwai Wa Cheng2, Shigeo Igarashi, Parimal S. Nathwani and Peter C. K. Leung3

Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5

Estrogen is one of the major sex steroid hormones that is produced from the human ovary, and its actions are established to be a receptor-mediated process. Despite the demonstration of estrogen receptor (ER) expression, little is known regarding the regulation of ER in the human ovary. In the present study we investigated the expression and hormonal regulation of ER{alpha} and ERß in human granulosa-luteal cells (hGLCs). Using RT-PCR amplification, both ER{alpha} and ERß messenger ribonucleic acid (mRNA) were detected from hGLCs. Northern blot analysis revealed that ER{alpha} is expressed at a relatively lower level than ERß. Basal expression studies indicated that ER{alpha} mRNA levels remain unchanged, whereas ERß mRNA levels increased with time in culture in vitro, suggesting that ERß is likely to play a dynamic role in mediating estrogen action in hGLCs.

The regulation of ER{alpha} and ERß expression by hCG was examined. hCG treatment (10 IU/mL) significantly attenuated the ER{alpha} (45%; P < 0.01) and ERß (40%; P < 0.01) mRNA levels. The hCG-induced decrease in ER{alpha} and ERß expression was mimicked by 8-bromo-cAMP (1 mmol/L) and forskolin (10 µmol/L) treatment. Additional studies using a specific protein kinase A (PKA) inhibitor (adenosine 3',5'-cyclic monophosphorothioate, Rp-isomer, triethylammonium salt) and an adenylate cyclase inhibitor (SQ 22536) further implicated the involvement of the cAMP/PKA signaling pathway in hCG action in these cells. The hCG-induced decrease in ER{alpha} and ERß mRNA levels was prevented in the presence of these inhibitors. Next, the effect of GnRH on ER expression was studied. Sixty-eight percent (P < 0.001) and 60% (P < 0.001) decreases in ER{alpha} and ERß mRNA levels, respectively, were observed after treatment with 0.1 µmol/L GnRH agonist (GnRHa). Pretreatment of the cells with a protein kinase C (PKC) inhibitor (GF109203X) completely reversed the GnRHainduced down-regulation of ER{alpha} and ERß expression, suggesting the involvement of PKC in GnRH signal transduction in hGLCs. In agreement with the semiquantitative RT-PCR results, Western blot analysis detected a decrease in ER{alpha} and ERß proteins levels in hGLCs after treatment with hCG (10 IU/mL), GnRH (0.1 µmol/L), 8-bromo-cAMP (1 mmol/L), forskolin (10 µmol/L), or phorbol 12-myristate 13 acetate (10 µmol/L). Functionally, we demonstrated an inhibition of progesterone production in hGLCs in vitro by 17ß-estradiol, and this inhibitory effect was eliminated by pretreatment of 10 IU/mL hCG or 0.1 µmol/L GnRHa for 24 h before 17ß-estradiol administration.

In summary, we observed a differential expression of ER{alpha} and ERß mRNA in hGLCs in vitro. The demonstration of hCG- and GnRHa-induced down-regulation of ER{alpha} and ERß gene expression suggests that hCG and GnRH may contribute to the control of granulosa-luteal cell function. Furthermore, our data suggest that the effects of hCG and GnRH on ER{alpha} and ERß expression in hGLCs are mediated in part by activation of PKA and PKC signaling pathways, respectively.




This article has been cited by other articles:


Home page
 ReproductionHome page
S. van den Driesche, V. M Smith, M. Myers, and W C. Duncan
Expression and regulation of oestrogen receptors in the human corpus luteum
Reproduction, April 1, 2008; 135(4): 509 - 517.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
P. Galluzzo, F. Caiazza, S. Moreno, and M. Marino
Role of ER{beta} palmitoylation in the inhibition of human colon cancer cell proliferation
Endocr. Relat. Cancer, March 1, 2007; 14(1): 153 - 167.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. A. Milne, T. A. Henderson, R. W. Kelly, P. T. Saunders, D. T. Baird, and H. O. D. Critchley
Leukocyte Populations and Steroid Receptor Expression in Human First-Trimester Decidua; Regulation by Antiprogestin and Prostaglandin E Analog
J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4315 - 4321.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. Yang, J. Wang, Y. Shen, and S. K. Roy
Developmental Expression of Estrogen Receptor (ER) {alpha} and ER{beta} in the Hamster Ovary: Regulation by Follicle-Stimulating Hormone
Endocrinology, December 1, 2004; 145(12): 5757 - 5766.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. J. Pinzone, H. Stevenson, J. S. Strobl, and P. E. Berg
Molecular and Cellular Determinants of Estrogen Receptor {alpha} Expression
Mol. Cell. Biol., June 1, 2004; 24(11): 4605 - 4612.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Khosravi and P. C. K. Leung
Differential Regulation of Gonadotropin-Releasing Hormone (GnRH)I and GnRHII Messenger Ribonucleic Acid by Gonadal Steroids in Human Granulosa Luteal Cells
J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 663 - 672.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. J. Jakimiuk, S. R. Weitsman, H.-W. Yen, M. Bogusiewicz, and D. A. Magoffin
Estrogen Receptor {alpha} and {beta} Expression in Theca and Granulosa Cells from Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5532 - 5538.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
P. Yang, A. Kriatchko, and S. K. Roy
Expression of ER-{alpha} and ER-{beta} in the Hamster Ovary: Differential Regulation by Gonadotropins and Ovarian Steroid Hormones
Endocrinology, June 1, 2002; 143(6): 2385 - 2398.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. F. Palter, A. B. Tavares, A. Hourvitz, J. D. Veldhuis, and E. Y. Adashi
Are Estrogens of Import to Primate/Human Ovarian Folliculogenesis?
Endocr. Rev., June 1, 2001; 22(3): 389 - 424.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Guo, L. Savage, K. D. Sarge, and O.-K. Park-Sarge
Gonadotropins Decrease Estrogen Receptor-{beta} Messenger Ribonucleic Acid Stability in Rat Granulosa Cells
Endocrinology, June 1, 2001; 142(6): 2230 - 2237.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2000 by The Endocrine Society