| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL) and Laval University, Quebec, Canada G1V 4G2
Address all correspondence and requests for reprints to: Professor Van Luu-The, Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (Centre Hospitalier Universitaire Laval), 2705 Laurier Boulevard, Quebec, Quebec, Canada G1V 4G2.
A novel 17ß-hydroxysteroid dehydrogenase (17ß-HSD) chronologically named type 12 17ß-HSD (17ß-HSD12), that transforms estrone (E1) into estradiol (E2) was identified by sequence similarity with type 3 17ß-HSD (17ß-HSD3) that catalyzes the formation of testosterone from androstenedione in the testis. Both are encoded by large genes spanning 11 exons, most of them showing identical size. Using human embryonic kidney-293 cells stably expressing 17ß-HSD12, we have found that the enzyme catalyzes selectively and efficiently the transformation of E1 into E2, thus identifying its role in estrogen formation, in contrast with 17ß-HSD3, the enzyme involved in the biosynthesis of the androgen testosterone in the testis. Using real-time PCR to quantify mRNA in a series of human tissues, the expression levels of 17ß-HSD12 as well as two other enzymes that perform the same transformation of E1 into E2, namely type 1 17ß-HSD and type 7 17ß-HSD, it was found that 17ß-HSD12 mRNA is the most highly expressed in the ovary and mammary gland. To obtain a better understanding of the structural basis of the difference in substrate specificity between 17ß-HSD3 and 17ß-HSD12, we have performed tridimensional structure modelization using the coordinates of type 1 17ß-HSD and site-directed mutagenesis. The results show the potential role of bulky amino acid F234 in 17ß-HSD12 that blocks the entrance of androstenedione. Overall, our results strongly suggest that 17ß-HSD12 is the major estrogenic 17ß-HSD responsible for the conversion of E1 to E2 in women, especially in the ovary, the predominant source of estrogens before menopause.
NURSA Molecule Pages Link:
This article has been cited by other articles:
![]() |
A. Jansson, L. Delander, C. Gunnarsson, T. Fornander, L. Skoog, B. Nordenskjold, and O. Stal Ratio of 17HSD1 to 17HSD2 Protein Expression Predicts the Outcome of Tamoxifen Treatment in Postmenopausal Breast Cancer Patients Clin. Cancer Res., May 15, 2009; 15(10): 3610 - 3616. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Delvoux, P. Groothuis, T. D'Hooghe, C. Kyama, G. Dunselman, and A. Romano Increased Production of 17{beta}-Estradiol in Endometriosis Lesions Is the Result of Impaired Metabolism J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 876 - 883. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Nagasaki, T. Suzuki, Y. Miki, J.-i. Akahira, K. Kitada, T. Ishida, H. Handa, N. Ohuchi, and H. Sasano 17{beta}-Hydroxysteroid Dehydrogenase Type 12 in Human Breast Carcinoma: A Prognostic Factor via Potential Regulation of Fatty Acid Synthesis Cancer Res., February 15, 2009; 69(4): 1392 - 1399. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M Day, H. J Tutill, A. Purohit, and M. J Reed Design and validation of specific inhibitors of 17{beta}-hydroxysteroid dehydrogenases for therapeutic application in breast and prostate cancer, and in endometriosis Endocr. Relat. Cancer, September 1, 2008; 15(3): 665 - 692. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Desnoyers, P.-G. Blanchard, J.-F. St-Laurent, S. N Gagnon, D. L Baillie, and V. Luu-The Caenorhabditis elegans LET-767 is able to metabolize androgens and estrogens and likely shares common ancestor with human types 3 and 12 17{beta}-hydroxysteroid dehydrogenases J. Endocrinol., November 1, 2007; 195(2): 271 - 279. [Abstract] [Full Text] [PDF] |
||||
![]() |
P.-G. Blanchard and V. Luu-The Differential androgen and estrogen substrates specificity in the mouse and primates type 12 17{beta}-hydroxysteroid dehydrogenase J. Endocrinol., August 1, 2007; 194(2): 449 - 455. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Rice and S. A Whitehead Phytoestrogens and breast cancer -promoters or protectors? Endocr. Relat. Cancer, December 1, 2006; 13(4): 995 - 1015. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. K. Jansson, C. Gunnarsson, M. Cohen, T. Sivik, and O. Stal 17{beta}-Hydroxysteroid Dehydrogenase 14 Affects Estradiol Levels in Breast Cancer Cells and Is a Prognostic Marker in Estrogen Receptor-Positive Breast Cancer Cancer Res., December 1, 2006; 66(23): 11471 - 11477. [Abstract] [Full Text] [PDF] |
||||
![]() |
A Jansson, C Gunnarsson, and O Stal Proliferative responses to altered 17{beta}-hydroxysteroid dehydrogenase (17HSD) type 2 expression in human breast cancer cells are dependent on endogenous expression of 17HSD type 1 and the oestradiol receptors. Endocr. Relat. Cancer, September 1, 2006; 13(3): 875 - 884. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Takase, M.-H. Levesque, V. Luu-The, M. El-Alfy, F. Labrie, and G. Pelletier Expression of Enzymes Involved in Estrogen Metabolism in Human Prostate J. Histochem. Cytochem., August 1, 2006; 54(8): 911 - 921. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |