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https://hdl.handle.net/2440/8389
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Type: | Journal article |
Title: | Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor |
Author: | Doyle, K. Russell, D. Sriraman, V. Richards, J. |
Citation: | Molecular Endocrinology, 2004; 18(10):2463-2478 |
Publisher: | Endocrine Soc |
Issue Date: | 2004 |
ISSN: | 0888-8809 1944-9917 |
Statement of Responsibility: | Kari M. H. Doyle, Darryl L. Russell, Venkataraman Sriraman and JoAnne S. Richards |
Abstract: | ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs) is a multifunctional protease that is expressed in periovulatory follicles. Herein we show that induction of ADAMTS-1 message in vivo and transcription of the ADAMTS-1 promoter in cultured granulosa cells are dependent on separable but coordinate actions of LH and the progesterone receptor (PR). To analyze the molecular mechanisms by which LH and PR regulate this gene, truncations and site-specific mutants of ADAMTS-1 promoter-luciferase reporter constructs (ADAMTS-1-Luc) were generated and transfected into rat granulosa cell cultures. Three regions of the promoter were found to be important for basal activity, two of which were guanine cytosine-rich binding sites for specificity proteins Sp1/Sp3 and the third bound a nuclear factor 1-like factor. Despite the absence of a consensus PR DNA response element in the proximal ADAMTS-1 promoter, cotransfection of a PRA (or PRB) expression vector stimulated ADAMTS-1 promoter activity, a response that was reduced by the PR antagonist ZK98299. Forskolin plus phorbol myristate acetate also increased promoter activity and, when added to cells cotransfected with PRA, ADAMTS-1 promoter activity increased further. Activation of the ADAMTS-1 promoter by PRA involves functional CAAT enhancer binding protein beta, nuclear factor 1-like factor, and three Sp1/Sp3 binding sites as demonstrated by transfection of mutated promoter constructs. In summary, LH and PRA/B exert distinct but coordinate effects on transactivation of the ADAMTS-1 gene in granulosa cells in vivo and in vitro with PR acting as an inducible coregulator of the ADAMTS-1 gene. |
Keywords: | Ovarian Follicle Granulosa Cells Animals Mice, Knockout Mice Rats Metalloendopeptidases Disintegrins Receptors, LH Receptors, Progesterone Transfection Sequence Alignment Transcription, Genetic Sequence Deletion Base Sequence Conserved Sequence Sequence Homology, Nucleic Acid Ovulation Genes, Reporter Molecular Sequence Data Female ADAM Proteins Promoter Regions, Genetic ADAMTS1 Protein |
Description: | Copyright © 2004 by The Endocrine Society |
DOI: | 10.1210/me.2003-0380 |
Published version: | http://dx.doi.org/10.1210/me.2003-0380 |
Appears in Collections: | Aurora harvest 4 Obstetrics and Gynaecology publications |
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