Endocrinology, Vol 131, 615-620, Copyright © 1992 by Endocrine Society

ARTICLES

Epidermal growth factor, a phorbol ester, and 3',5'-cyclic adenosine monophosphate decrease the transcription of the luteinizing hormone/chorionic gonadotropin receptor gene in MA-10 Leydig tumor cells

S Nelson and M Ascoli
Department of Pharmacology, The University of Iowa College of Medicine, Iowa City, Iowa 52242.

In a recent series of experiments we have shown that the previously recognized ability of mouse epidermal growth factor (mEGF), cAMP, or phorbol 12-myristate 13-acetate (PMA) to reduce the density of LH/CG receptors in MA-10 cells is secondary to a reduction in receptor messenger RNA (mRNA). As a follow-up to these studies we now present experiments designed to determine if the reduction in LH/CG receptor mRNA is due to a decrease in transcription of the receptor gene and/or an increase in the rate of degradation of the mRNA. The potential effects of mEGF, cAMP, or PMA on the degradation of the LH/CG receptor mRNA were measured in MA-10 cells treated with Actinomycin D or in kidney cells permanently transfected with the LH/CG receptor complementary DNA driven by a heterologous promoter. Both experimental strategies revealed that none of these compounds increase the rate of degradation of the receptor mRNA. If anything, a stabilizing effect was noted. The potential effects of mEGF, cAMP, or PMA on the transcription of the LH/CG receptor gene in MA-10 cells were measured using nuclear run-off assays. All three compounds induced a rapid decrease in the transcription of the LH/CG receptor gene. The time course of these effects is similar, and by 2 h all of the stimuli had decreased transcription to 15-30% of control. Our studies show that the mEGF-, cAMP- and PMA-induced down-regulation of the LH/CG receptor in MA-10 cells is primarily (if not entirely) due to a decrease in the transcription of the receptor gene.

This article has been cited by other articles:

				H. Youn, Y. Koo, I. Ji, and T. H. Ji An Upstream Initiator-Like Element Suppresses Transcription of the Rat Luteinizing Hormone Receptor Gene Mol. Endocrinol., May 1, 2005; 19(5): 1318 - 1328. [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]

				V. M. Laurich, A. M. Trbovich, F. H. O'Neill, C. P. Houk, P. M. Sluss, A. H. Payne, P. K. Donahoe, and J. Teixeira Mullerian Inhibiting Substance Blocks the Protein Kinase A-Induced Expression of Cytochrome P450 17{alpha}-Hydroxylase/C17-20 Lyase mRNA in a Mouse Leydig Cell Line Independent of cAMP Responsive Element Binding Protein Phosphorylation Endocrinology, September 1, 2002; 143(9): 3351 - 3360. [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]

				T. Hirakawa, C. Galet, and M. Ascoli MA-10 Cells Transfected with the Human Lutropin/Choriogonadotropin Receptor (hLHR): A Novel Experimental Paradigm to Study the Functional Properties of the hLHR Endocrinology, March 1, 2002; 143(3): 1026 - 1035. [Abstract] [Full Text] [PDF]

				A. P. N. Themmen and I. T. Huhtaniemi Mutations of Gonadotropins and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function Endocr. Rev., October 1, 2000; 21(5): 551 - 583. [Abstract] [Full Text]

				T. El-Hefnawy, P. R. Manna, M. Luconi, E. Baldi, J. P. Slotte, and I. Huhtaniemi Progesterone Action in a Murine Leydig Tumor Cell Line (mLTC-1), Possibly through a Nonclassical Receptor Type Endocrinology, January 1, 2000; 141(1): 247 - 255. [Abstract] [Full Text] [PDF]

				K. Nakamura, M. d. F. M. Lazari, S. Li, C. Korgaonkar, and M. Ascoli Role of the Rate of Internalization of the Agonist-Receptor Complex on the Agonist-Induced Down-Regulation of the Lutropin/ Choriogonadotropin Receptor Mol. Endocrinol., August 1, 1999; 13(8): 1295 - 1304. [Abstract] [Full Text]

				N. Pescador, D. M. Stocco, and B. D. Murphy Growth Factor Modulation of Steroidogenic Acute Regulatory Protein and Luteinization in the Pig Ovary Biol Reprod, June 1, 1999; 60(6): 1453 - 1461. [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]

				G. Aleppo, S. F. Moskal II, P. A. De Grandis, R. D. Kineman, and L. A. Frohman Homologous Down-Regulation of Growth Hormone-Releasing Hormone Receptor Messenger Ribonucleic Acid Levels Endocrinology, March 1, 1997; 138(3): 1058 - 1065. [Abstract] [Full Text] [PDF]