Endocrinology, Vol 130, 1309-1317, Copyright © 1992 by Endocrine Society

ARTICLES

P450(17 alpha) and P450SCC gene expression and regulation in the rat placenta

TJ Durkee, MP McLean, DB Hales, AH Payne, MR Waterman, I Khan and G Gibori
Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612.

To examine the developmental expression and regulation of P450SCC and P450(17 alpha) in the rat placenta, trophoblast and decidual tissue were removed by dissection from conceptuses obtained from rats on selected days of pregnancy. Total cellular and poly(A)+ RNA and microsomal and mitochondrial fractions were isolated and analyzed for the presence of P450(17) alpha and P450SCC messenger RNA (mRNA) and protein by Northern and Western blot analysis. P450(17) alpha and P450SCC mRNA were detected in the trophoblast but not in the decidual tissue. Western blot studies demonstrated that the immunoreactive P450(17) alpha in the rat placenta is a 79-kilodalton protein, having a slower mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than has been reported for other tissue. Antiserum preabsorbed with pure P450(17) alpha was unable to detect this protein, and immunoprecipitation indicated that it is associated with enzyme activity. Development studies have revealed that the two steroidogenic enzymes are differentially expressed during the progression of pregnancy. Whereas P450SCC mRNA and protein increase abruptly between days 10-12 of pregnancy, decline thereafter, and remain low, those of P450(17) alpha increase slowly and progressively, peaking on day 18 and declining just before parturition. It is the changes in P450(17) alpha and not that of P450SCC which appear to be intimately linked to the previously reported changes in placental production of androgen. To examine whether P450(17) alpha and/or P450SCC became expressed from midpregnancy because of the rapid decline in LH that occurs at this stage, pregnant rats were treated with low but sustained levels of human CG (hCG) in order to prevent the drop in LH activity. hCG treatment caused a remarkable down regulation in the expression of both P450SCC and P450(17) alpha message and protein. In summary, the results of this investigation have established, for the first time, the presence of messages for both P450(17) alpha and P450SCC in the trophoblast tissue forming the rat placenta. The results have revealed that these two enzymes are differentially expressed during the progression of pregnancy and that the expression of their genes is down- regulated by LH/hCG.

This article has been cited by other articles:

				N. Sher, N. Yivgi-Ohana, and J. Orly Transcriptional Regulation of the Cholesterol Side Chain Cleavage Cytochrome P450 Gene (CYP11A1) Revisited: Binding of GATA, Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and Activating Protein (AP)-1 Proteins to a Distal Novel Cluster of cis-Regulatory Elements Potentiates AP-2 and Steroidogenic Factor-1-Dependent Gene Expression in the Rodent Placenta and Ovary Mol. Endocrinol., April 1, 2007; 21(4): 948 - 962. [Abstract] [Full Text] [PDF]

				S. H. Mellon, S. R. Bair, C. Depoix, J.-L. Vigne, N. B. Hecht, and P. B. Brake Translin Coactivates Steroidogenic Factor-1-Stimulated Transcription Mol. Endocrinol., January 1, 2007; 21(1): 89 - 105. [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, Y. Huang, F. Jin, S.-W. Jiang, and A. H. Payne Transcription Enhancer Factor-5 and a GATA-Like Protein Determine Placental-Specific Expression of the Type I Human 3{beta}-Hydroxysteroid Dehydrogenase Gene, HSD3B1 Mol. Endocrinol., August 1, 2004; 18(8): 2049 - 2060. [Abstract] [Full Text] [PDF]

				S. R. Bair and S. H. Mellon Deletion of the Mouse P450c17 Gene Causes Early Embryonic Lethality Mol. Cell. Biol., June 15, 2004; 24(12): 5383 - 5390. [Abstract] [Full Text] [PDF]

				C. E. Fluck and W. L. Miller GATA-4 and GATA-6 Modulate Tissue-Specific Transcription of the Human Gene for P450c17 by Direct Interaction with Sp1 Mol. Endocrinol., May 1, 2004; 18(5): 1144 - 1157. [Abstract] [Full Text] [PDF]

				M. Ben-Zimra, M. Koler, and J. Orly Transcription of Cholesterol Side-Chain Cleavage Cytochrome P450 in the Placenta: Activating Protein-2 Assumes the Role of Steroidogenic Factor-1 by Binding to an Overlapping Promoter Element Mol. Endocrinol., August 1, 2002; 16(8): 1864 - 1880. [Abstract] [Full Text] [PDF]

				J. R. Schwartz and S. K. Roy Developmental Expression of Cytochrome P450 Side-Chain Cleavage and Cytochrome P450 17{alpha}-Hydroxylase Messenger Ribonucleic Acid and Protein in the Neonatal Hamster Ovary Biol Reprod, December 1, 2000; 63(6): 1586 - 1593. [Abstract] [Full Text]

				J. Arensburg, A. H. Payne, and J. Orly Expression of Steroidogenic Genes in Maternal and Extraembryonic Cells During Early Pregnancy in Mice Endocrinology, November 1, 1999; 140(11): 5220 - 5232. [Abstract] [Full Text]

				X. Chu, C. J. Corbin, M. A. Kaminski, and A. J. Conley Unique Regulation of CYP17 Expression in the Trophectoderm of the Preattachment Porcine Blastocyst Endocrinology, February 1, 1999; 140(2): 632 - 640. [Abstract] [Full Text]

				L. A. Akinola, M. Poutanen, R. Vihko, and P. Vihko Expression of 17{beta}-Hydroxysteroid Dehydrogenase Type 1 and Type 2, P450 Aromatase, and 20{alpha}-Hydroxysteroid Dehydrogenase Enzymes in Immature, Mature, and Pregnant Rats Endocrinology, July 1, 1997; 138(7): 2886 - 2892. [Abstract] [Full Text] [PDF]

				P. Zhang and S. H. Mellon Multiple Orphan Nuclear Receptors Converge to Regulate Rat P450c17 Gene Transcription: Novel Mechanisms for Orphan Nuclear Receptor Action Mol. Endocrinol., June 1, 1997; 11(7): 891 - 904. [Abstract] [Full Text]