Molecular Endocrinology, Vol 7, 355-364, Copyright © 1993 by Endocrine Society

ARTICLES

Regulation of 3 beta-hydroxysteroid dehydrogenase and 17 beta- hydroxysteroid dehydrogenase messenger ribonucleic acid levels by cyclic adenosine 3',5'-monophosphate and phorbol myristate acetate in human choriocarcinoma cells

Y Tremblay and C Beaudoin
Department of Physiology, Laval University Centre Hospitalier de l'Universite Laval Sainte-Foy, Quebec, Canada.

3 beta-Hydroxysteroid dehydrogenase (3 beta HSD) in human placenta converts 3 beta-hydroxy-5-ene steroids producing progesterone, whereas 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) mediates the interconversion of estrone and estradiol. We first showed that the expression of type I 17 beta HSD (17 beta HSD-I) gene was undetectable in human JEG-3 cells. We then studied the effects of cAMP- and protein kinase-C-dependent pathways on the expression of 3 beta HSD-I and 17 beta HSD-II genes using an analog of cAMP [8-(4-chlorophenylthio)cAMP (8CPTcAMP)] and a protein kinase-C (PKC) activator, phorbol 12- myristate 13-acetate (PMA), in JEG-3 cells. Novel inhibitors of protein kinase-A (PKA) and PKC were also used. The 3 beta HSD cDNA probe hybridized to a single 1.7-kilobase (kb) 3 beta HSD mRNA species corresponding to the transcript of the 3 beta HSD-I gene. The 17 beta HSD cDNA probe hybridized to two 17 beta HSD transcripts of 1.3 and 2.2 kb. The 1.3-kb 17 beta HSD mRNA species was regulated, whereas the 2.2- kb species was constitutively expressed in JEG-3 cells. When JEG-3 cells were exposed to 8CPTcAMP or PMA, 3 beta HSD-I and 17 beta HSD-II gene transcriptions were increased in a dose- and time-dependent manner. Moreover, the combined effects of PMA and 8CPTcAMP on 3 beta HSD-I mRNA levels was additive and synergistic on 17 beta HSD-II mRNA levels. The mechanism by which cAMP activated accumulation of 3 beta HSD-I and 17 beta HSD-II mRNAs involved an activation of the cyclase. The effects of a cAMP-dependent kinase inhibitor and a diacylglycerol- dependent kinase inhibitor in JEG-3 cells indicated that cAMP acts on 3 beta HSD-I mRNA via a PKA-dependent mechanism, but on 17 beta HSD-II mRNA via another nonclassical cAMP-dependent mechanism. Finally, the effect of activation of both signaling pathways on expression of the 17 beta HSD-II gene as well as the effect of PMA on the 3 beta HSD-I gene did not require protein synthesis. These data provide strong evidence for the regulation of the 3 beta HSD-I and 17 beta HSD-II genes by cAMP and PKC and, thus, indicate an important endocrine and/or paracrine regulation of steroid hormone production in human placenta.

This article has been cited by other articles:

				H. A. LaVoie and S. R. King Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B Experimental Biology and Medicine, August 1, 2009; 234(8): 880 - 907. [Abstract] [Full Text] [PDF]

				T. Suzuki, Y. Miki, Y. Nakamura, T. Moriya, K. Ito, N. Ohuchi, and H. Sasano Sex steroid-producing enzymes in human breast cancer Endocr. Relat. Cancer, December 1, 2005; 12(4): 701 - 720. [Abstract] [Full Text] [PDF]

				J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family Endocr. Rev., June 1, 2005; 26(4): 525 - 582. [Abstract] [Full Text] [PDF]

				A. H. Payne and D. B. Hales Overview of Steroidogenic Enzymes in the Pathway from Cholesterol to Active Steroid Hormones Endocr. Rev., December 1, 2004; 25(6): 947 - 970. [Abstract] [Full Text] [PDF]

				L. Peng and A. H. Payne AP-2gamma and the Homeodomain Protein Distal-less 3 Are Required for Placental-specific Expression of the Murine 3beta -Hydroxysteroid Dehydrogenase VI Gene, Hsd3b6 J. Biol. Chem., March 1, 2002; 277(10): 7945 - 7954. [Abstract] [Full Text] [PDF]

				M. Bonenfant, C. H. Blomquist, P. R. Provost, R. Drolet, P. D’Ascoli, and Y. Tremblay Tissue- and Site-Specific Gene Expression of Type 2 17{beta}-Hydroxysteroid Dehydrogenase: In Situ Hybridization and Specific Enzymatic Activity Studies in Human Placental Endothelial Cells of the Arterial System J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4841 - 4850. [Abstract] [Full Text]

				P. R. Provost, C. H. Blomquist, C. Godin, X.-F. Huang, N. Flamand, V. Luu-The, D. Nadeau, and Y. Tremblay Androgen Formation and Metabolism in the Pulmonary Epithelial Cell Line A549: Expression of 17{beta}-Hydroxysteroid Dehydrogenase Type 5 and 3{alpha}-Hydroxysteroid Dehydrogenase Type 3 Endocrinology, August 1, 2000; 141(8): 2786 - 2794. [Abstract] [Full Text] [PDF]

				S. Leivonen, Y.-s. Piao, H. Peltoketo, P. Numchaisrika, R. Vihko, and P. Vihko Identification of Essential Subelements in the hHSD17B1 Enhancer: Difference in Function of the Enhancer and That of the hHSD17BP1 Analog Is due to -480C and -486G Endocrinology, August 1, 1999; 140(8): 3478 - 3487. [Abstract] [Full Text]

				A. G. Mensah-Nyagan, J.-L. Do-Rego, D. Beaujean, V. Luu-The, G. Pelletier, and H. Vaudry Neurosteroids: Expression of Steroidogenic Enzymes and Regulation of Steroid Biosynthesis in the Central Nervous System Pharmacol. Rev., March 1, 1999; 51(1): 63 - 82. [Abstract] [Full Text] [PDF]

				M. V. J. Mustonen, V. V. Isomaa, T. Vaskivuo, J. Tapanainen, M. H. Poutanen, F. Stenbäck, R. K. Vihko, and P. T. Vihko Human 17{beta}-Hydroxysteroid Dehydrogenase Type 2 Messenger Ribonucleic Acid Expression and Localization in Term Placenta and in Endometrium during the Menstrual Cycle J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1319 - 1324. [Abstract] [Full Text]

				Y.-s. Piao, H. Peltoketo, P. Vihko, and R. Vihko The Proximal Promoter Region of the Gene Encoding Human 17{beta}-Hydroxysteroid Dehydrogenase Type 1 Contains GATA, AP-2, and Sp1 Response Elements: Analysis of Promoter Function in Choriocarcinoma Cells Endocrinology, August 1, 1997; 138(8): 3417 - 3425. [Abstract] [Full Text] [PDF]

				T. M. Penning Molecular Endocrinology of Hydroxysteroid Dehydrogenases Endocr. Rev., June 1, 1997; 18(3): 281 - 305. [Abstract] [Full Text]

				S. Leers-Sucheta, K.-i. Morohashi, J. I. Mason, and M. H. Melner Synergistic Activation of the Human Type II 3beta -Hydroxysteroid Dehydrogenase/Delta 5-Delta 4 Isomerase Promoter by the Transcription Factor Steroidogenic Factor-1/Adrenal 4-binding Protein and Phorbol Ester J. Biol. Chem., March 21, 1997; 272(12): 7960 - 7967. [Abstract] [Full Text] [PDF]

				Y.-s. Piao, H. Peltoketo, A. Jouppila, and R. Vihko Retinoic Acids Increase 17{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression in JEG-3 and T47D Cells, but the Stimulation Is Potentiated by Epidermal Growth Factor, 12-O-Tetradecanoylphorbol-13-Acetate, and Cyclic Adenosine 3',5'-Monophosphate Only in JEG-3 Cells Endocrinology, March 1, 1997; 138(3): 898 - 904. [Abstract] [Full Text] [PDF]

				P. R. Provost and Y. Tremblay Length Increase of the Human alpha -Globin 3'-Untranslated Region Disrupts Stability of the Pre-mRNA but Not That of the Mature mRNA J. Biol. Chem., September 22, 2000; 275(39): 30248 - 30255. [Abstract] [Full Text] [PDF]