Molecular Endocrinology, Vol 9, 734-744, Copyright © 1995 by Endocrine Society

ARTICLES

A role for increased lutropin/choriogonadotropin receptor (LHR) gene transcription in the follitropin-stimulated induction of the LHR in granulosa cells

H Shi and DL Segaloff
Department of Physiology, University of Iowa College of Medicine, Iowa City 52242, USA.

Follitropin (FSH) has been shown in previous studies to stimulate the induction of the LH/CG receptor (LHR) and LHR mRNA in the granulosa cells of diethylstilbesterol-primed immature rats. The present studies were undertaken to identify the mechanisms underlying the hormone- dependent induction of the LHR in rat granulosa cells. The effect of FSH on LHR mRNA stability was determined by measuring the decay of LHR mRNA after removal of FSH under conditions where transcription was inhibited. Under these conditions, readdition of FSH had little effect on mRNA stability. However, inhibitors of transcription themselves were found to have a marked effect on stabilizing the LHR mRNA, thus potentially masking an effect of FSH. These results suggest that there is a labile destabilizing factor that constitutively degrades LHR mRNA. At present, it cannot be ascertained whether FSH has any effect on this destabilizing factor. Transcriptional activity of the LHR gene was examined using nuclear run-on assays. It was found that 1) in the absence of FSH, LHR-binding activity and mRNA levels were negligible, but the LHR gene was transcriptionally active in granulosa cells of immature rats; 2) incubations of granulosa cells with FSH or 8-bromo- cAMP significantly increased endogenous LHR gene transcription (approximately 10-fold) under conditions where increases in LHR mRNA were observed; 3) the continuous presence of FSH or 8-bromo-cAMP was required to maintain elevated levels of LHR gene transcription and LHR mRNA; and 4) exogenous estradiol alone had no effect on transcription of the LHR gene although it was able to synergistically enhance FSH- induced LHR expression. These experiments suggest that while the effects of estradiol on LHR induction do not appear to be mediated by an increase in LHR gene transcription, the effects of FSH (or cAMP) on LHR induction are clearly mediated, at least in part, by significant increases in the rate of LHR gene transcription.

This article has been cited by other articles:

				S. W. Warrenfeltz, S. A. Lott, T. M. Palmer, J. C. Gray, and D. Puett Luteinizing Hormone-Induced Up-Regulation of ErbB-2 Is Insufficient Stimulant of Growth and Invasion in Ovarian Cancer Cells Mol. Cancer Res., November 1, 2008; 6(11): 1775 - 1785. [Abstract] [Full Text] [PDF]

				S. Ikeda, K. Nakamura, K. Kogure, Y. Omori, S. Yamashita, K. Kubota, T. Mizutani, K. Miyamoto, and T. Minegishi Effect of Estrogen on the Expression of Luteinizing Hormone-Human Chorionic Gonadotropin Receptor Messenger Ribonucleic Acid in Cultured Rat Granulosa Cells Endocrinology, April 1, 2008; 149(4): 1524 - 1533. [Abstract] [Full Text] [PDF]

				N. Andric and M. Ascoli A Delayed Gonadotropin-Dependent and Growth Factor-Mediated Activation of the Extracellular Signal-Regulated Kinase 1/2 Cascade Negatively Regulates Aromatase Expression in Granulosa Cells Mol. Endocrinol., December 1, 2006; 20(12): 3308 - 3320. [Abstract] [Full Text] [PDF]

				M. Xu, E. West, L. D. Shea, and T. K. Woodruff Identification of a Stage-Specific Permissive In Vitro Culture Environment for Follicle Growth and Oocyte Development Biol Reprod, December 1, 2006; 75(6): 916 - 923. [Abstract] [Full Text] [PDF]

				F. X. Donadeu and M. Ascoli The Differential Effects of the Gonadotropin Receptors on Aromatase Expression in Primary Cultures of Immature Rat Granulosa Cells Are Highly Dependent on the Density of Receptors Expressed and the Activation of the Inositol Phosphate Cascade Endocrinology, September 1, 2005; 146(9): 3907 - 3916. [Abstract] [Full Text] [PDF]

				H.-F. Kwok, W.-K. So, Y. Wang, and W. Ge Zebrafish Gonadotropins and Their Receptors: I. Cloning and Characterization of Zebrafish Follicle-Stimulating Hormone and Luteinizing Hormone Receptors-- Evidence for Their Distinct Functions in Follicle Development Biol Reprod, June 1, 2005; 72(6): 1370 - 1381. [Abstract] [Full Text] [PDF]

				M. Yang, Z. M. Lei, and Ch. V. Rao The Central Role of Human Chorionic Gonadotropin in the Formation of Human Placental Syncytium Endocrinology, March 1, 2003; 144(3): 1108 - 1120. [Abstract] [Full Text] [PDF]

				S. Eimerl and J. Orly Regulation of Steroidogenic Genes by Insulin-Like Growth Factor-1 and Follicle-Stimulating Hormone: Differential Responses of Cytochrome P450 Side-Chain Cleavage, Steroidogenic Acute Regulatory Protein, and 3{beta}-Hydroxysteroid Dehydrogenase/Isomerase in Rat Granulosa Cells Biol Reprod, September 1, 2002; 67(3): 900 - 910. [Abstract] [Full Text] [PDF]

				K. Inoue, K. Nakamura, K. Abe, T. Hirakawa, M. Tsuchiya, H. Matsuda, K. Miyamoto, and T. Minegishi Effect of Transforming Growth Factor {beta} on the Expression of Luteinizing Hormone Receptor in Cultured Rat Granulosa Cells Biol Reprod, August 1, 2002; 67(2): 610 - 615. [Abstract] [Full Text] [PDF]

				M. Yoshino, T. Mizutani, K. Yamada, M. Tsuchiya, T. Minegishi, T. Yazawa, H. Kawata, T. Sekiguchi, T. Kajitani, and K. Miyamoto Early Growth Response Gene-1 Regulates the Expression of the Rat Luteinizing Hormone Receptor Gene Biol Reprod, June 1, 2002; 66(6): 1813 - 1819. [Abstract] [Full Text] [PDF]

				M. Ascoli, F. Fanelli, and D. L. Segaloff The Lutropin/Choriogonadotropin Receptor, A 2002 Perspective Endocr. Rev., April 1, 2002; 23(2): 141 - 174. [Abstract] [Full Text] [PDF]

				S. Chen, X. Liu, and D. L. Segaloff Identification of an SAS (Sp1c Adjacent Site)-Like Element in the Distal 5'-Flanking Region of the Rat Lutropin Receptor Gene Essential for Cyclic Adenosine 3',5'-Monophosphate Responsiveness Endocrinology, May 1, 2001; 142(5): 2013 - 2021. [Abstract] [Full Text]

				S. Chen, X. Liu, and D. L. Segaloff A Novel Cyclic Adenosine 3',5'-Monophosphate-Responsive Element Involved In the Transcriptional Regulation of the Lutropin Receptor Gene in Granulosa Cells Mol. Endocrinol., September 1, 2000; 14(9): 1498 - 1508. [Abstract] [Full Text]

				T. Hirakawa, T. Minegishi, K. Abe, H. Kishi, Y. Ibuki, and K. Miyamoto A Role of Insulin-Like Growth Factor I in Luteinizing Hormone Receptor Expression in Granulosa Cells Endocrinology, November 1, 1999; 140(11): 4965 - 4971. [Abstract] [Full Text]

				T. Hirakawa, T. Minegishi, M. Tano, T. Kameda, H. Kishi, Y. Ibuki, T. Mizutani, and K. Miyamoto Effect of Prolactin on the Expression of Luteinizing Hormone Receptors during Cell Differentiation in Cultured Rat Granulosa Cells Endocrinology, August 1, 1999; 140(8): 3444 - 3451. [Abstract] [Full Text]

				S. Chen, H. Shi, X. Liu, and D. L. Segaloff Multiple Elements and Protein Factors Coordinate the Basal and Cyclic Adenosine 3',5'-Monophosphate-Induced Transcription of the Lutropin Receptor Gene in Rat Granulosa Cells Endocrinology, May 1, 1999; 140(5): 2100 - 2109. [Abstract] [Full Text]

				F.-P. Zhang, T. El-Hafnawy, and I. Huhtaniemi Regulation of Luteinizing Hormone Receptor Gene Expression by Insulin-Like Growth Factor-I in an Immortalized Murine Leydig Tumor Cell Line (BLT-1) Biol Reprod, November 1, 1998; 59(5): 1116 - 1123. [Abstract] [Full Text]

				X. Wang, G. Nickenig, and T. J. Murphy The Vascular Smooth Muscle Type I Angiotensin II Receptor mRNA Is Destabilized by Cyclic AMP-Elevating Agents Mol. Pharmacol., November 1, 1997; 52(5): 781 - 787. [Abstract] [Full Text]

				R. Ouali, M.-C. Berthelon, M. Begeot, and J. M. Saez Angiotensin II Receptor Subtypes AT1 and AT2 Are Down-Regulated by Angiotensin II through AT1 Receptor by Different Mechanisms Endocrinology, February 1, 1997; 138(2): 725 - 733. [Abstract] [Full Text] [PDF]

				A. Herrlich, B. Kuhn, R. Grosse, A. Schmid, G. Schultz, and T. Gudermann Involvement of Gs and Gi Proteins in Dual Coupling of the Luteinizing Hormone Receptor to Adenylyl Cyclase and Phospholipase C J. Biol. Chem., July 12, 1996; 271(28): 16764 - 16772. [Abstract] [Full Text] [PDF]