This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mahendroo, M. S. Articles by Russell, D. W. Search for Related Content PubMed PubMed Citation Articles by Mahendroo, M. S. Articles by Russell, D. W.

Fetal Death in Mice Lacking 5-Reductase Type 1 Caused by Estrogen Excess

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9046

Female mice deficient in steroid 5-reductase type 1 have a decreased litter size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups in wild type controls. Oogenesis, fertilization, implantation, and placental morphology appear normal in the mutant animals. Fetal loss occurs between gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental androgen production and an induction of 5-reductase type 1 expression in the decidua of wild type mice. Plasma levels of androstenedione and testosterone are 2- to 3-fold higher on gestation day 9, and estradiol levels are chronically elevated by 2- to 3-fold throughout early and midgestation in the knockout mice. Administration of an estrogen receptor antagonist or inhibitors of aromatase reverse the high rate of fetal death in the mutant mice, and estradiol treatment of wild type pregnant mice causes fetal wastage. The results suggest that in the deficient mice, a failure to 5-reduce androgens leads to their conversion to estrogens, which in turn causes fetal death in midgestation. These findings indicate that the 5-reduction of androgens in female animals plays a crucial role in guarding against estrogen toxicity during pregnancy.

This article has been cited by other articles:

				P. Rantakari, L. Strauss, R. Kiviranta, H. Lagerbohm, J. Paviala, I. Holopainen, S. Vainio, P. Pakarinen, and M. Poutanen Placenta Defects and Embryonic Lethality Resulting from Disruption of Mouse Hydroxysteroid (17-{beta}) Dehydrogenase 2 Gene Mol. Endocrinol., March 1, 2008; 22(3): 665 - 675. [Abstract] [Full Text] [PDF]

				G. Delbes, C. Levacher, and R. Habert Estrogen effects on fetal and neonatal testicular development. Reproduction, October 1, 2006; 132(4): 527 - 538. [Abstract] [Full Text] [PDF]

				J M Torres and E Ortega Steroid 5{alpha}-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone. J. Mol. Endocrinol., April 1, 2006; 36(2): 239 - 245. [Abstract] [Full Text] [PDF]

				H. Wang, S. Tranguch, H. Xie, G. Hanley, S. K. Das, and S. K. Dey Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus PNAS, July 12, 2005; 102(28): 9960 - 9965. [Abstract] [Full Text] [PDF]

				K. J. Straach, J. M. Shelton, J. A. Richardson, V. C. Hascall, and M. S. Mahendroo Regulation of hyaluronan expression during cervical ripening Glycobiology, January 1, 2005; 15(1): 55 - 65. [Abstract] [Full Text] [PDF]

				J. M. TORRES and E. ORTEGA Differential regulation of steroid 5{alpha}-reductase isozymes expression by androgens in the adult rat brain FASEB J, August 1, 2003; 17(11): 1428 - 1433. [Abstract] [Full Text] [PDF]

				R. M. Martin, C. J. Lin, M. Y. Nishi, A. E. C. Billerbeck, A. C. Latronico, D. W. Russell, and B. B. Mendonca Familial Hyperestrogenism in Both Sexes: Clinical, Hormonal, and Molecular Studies of Two Siblings J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3027 - 3034. [Abstract] [Full Text] [PDF]

				Z. Chai, P. Brereton, T. Suzuki, H. Sasano, V. Obeyesekere, G. Escher, R. Saffery, P. Fuller, C. Enriquez, and Z. Krozowski 17{beta}-Hydroxysteroid Dehydrogenase Type XI Localizes to Human Steroidogenic Cells Endocrinology, May 1, 2003; 144(5): 2084 - 2091. [Abstract] [Full Text] [PDF]

				R. J. Mann, R. A. Keri, and J. H. Nilson Consequences of Elevated Luteinizing Hormone on Diverse Physiological Systems: Use of the LH{beta}CTP Transgenic Mouse as a Model of Ovarian Hyperstimulation-induced Pathophysiology Recent Prog. Horm. Res., January 1, 2003; 58(1): 343 - 375. [Abstract] [Full Text] [PDF]

				N. J. Place, K. E. Holekamp, C. L. Sisk, M. L. Weldele, E. M. Coscia, C. M. Drea, and S. E. Glickman Effects of Prenatal Treatment with Antiandrogens on Luteinizing Hormone Secretion and Sex Steroid Concentrations in Adult Spotted Hyenas, Crocuta crocuta Biol Reprod, November 1, 2002; 67(5): 1405 - 1413. [Abstract] [Full Text] [PDF]

				Z. Weihua, J. Ekman, A. Almkvist, S. Saji, L. Wang, M. Warner, and J.-A. Gustafsson Involvement of Androgen Receptor in 17{beta}-Estradiol-Induced Cell Proliferation in Rat Uterus Biol Reprod, August 1, 2002; 67(2): 616 - 623. [Abstract] [Full Text] [PDF]

				I. M. Adham, G. Steding, T. Thamm, E. E. Bullesbach, C. Schwabe, I. Paprotta, and W. Engel The Overexpression of the Insl3 in Female Mice Causes Descent of the Ovaries Mol. Endocrinol., February 1, 2002; 16(2): 244 - 252. [Abstract] [Full Text] [PDF]

				G. Leonardsson, M. A. Jacobs, R. White, R. Jeffery, R. Poulsom, S. Milligan, and M. Parker Embryo Transfer Experiments and Ovarian Transplantation Identify the Ovary as the Only Site in Which Nuclear Receptor Interacting Protein 1/RIP140 Action Is Crucial for Female Fertility Endocrinology, February 1, 2002; 143(2): 700 - 707. [Abstract] [Full Text] [PDF]

				M. S. Mahendroo, K. M. Cala, D. L. Hess, and D. W. Russell Unexpected Virilization in Male Mice Lacking Steroid 5{alpha}-Reductase Enzymes Endocrinology, November 1, 2001; 142(11): 4652 - 4662. [Abstract] [Full Text] [PDF]

				S. Nef and L. F. Parada Hormones in male sexual development Genes & Dev., December 15, 2000; 14(24): 3075 - 3086. [Full Text]

				W.-C. Song and M. H. Melner Editorial: Steroid Transformation Enzymes as Critical Regulators of Steroid Action in Vivo Endocrinology, May 1, 2000; 141(5): 1587 - 1589. [Full Text] [PDF]

				D. O. Hardy, R.-S. Ge, J. F. Catterall, Y.-t. Hou, T. M. Penning, and M. P. Hardy Identification of the Oxidative 3{alpha}-Hydroxysteroid Dehydrogenase Activity of Rat Leydig Cells as Type II Retinol Dehydrogenase Endocrinology, May 1, 2000; 141(5): 1608 - 1617. [Abstract] [Full Text] [PDF]

				R.K. Bartholomeusz, N.W. Bruce, and A.-M. Lynch Embryo Survival, and Fetal and Placental Growth Following Elevation of Maternal Estradiol Blood Concentrations in the Rat Biol Reprod, July 1, 1999; 61(1): 46 - 50. [Abstract] [Full Text]

				R. J. Mann, R. A. Keri, and J. H. Nilson Transgenic Mice with Chronically Elevated Luteinizing Hormone Are Infertile Due to Anovulation, Defects in Uterine Receptivity, and Midgestation Pregnancy Failure Endocrinology, June 1, 1999; 140(6): 2592 - 2601. [Abstract] [Full Text]

				A. Kamat, K. H. Graves, M. E. Smith, J. A. Richardson, and C. R. Mendelson A 500-bp region, approx 40 kb upstream of the human CYP19 () gene, mediates placenta-specific expression in transgenic mice PNAS, April 13, 1999; 96(8): 4575 - 4580. [Abstract] [Full Text] [PDF]

				A. Poletti, P. Negri-Cesi, M. Rabuffetti, A. Colciago, F. Celotti, and L. Martini Transient Expression of the 5{alpha}-Reductase Type 2 Isozyme in the Rat Brain in Late Fetal and Early Postnatal Life Endocrinology, April 1, 1998; 139(4): 2171 - 2178. [Abstract] [Full Text] [PDF]

				D. Deplewski, S. Liao, and R. L. Rosenfield Preputial Sebocyte 5{alpha}-Reductase Isoform Specificity Endocrinology, October 1, 1997; 138(10): 4416 - 4420. [Abstract] [Full Text] [PDF]