| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA
1 Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
2 Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
(Requests for offprints should be addressed to Prema Narayan; Email: narayan{at}bmb.uga.edu)
(Thomas P Meehan is now at Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA)
(Megan E Overcast is now at Department of Molecular Genetics, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC, USA)
To study the effects of premature and chronic ligand-mediated luteinizing hormone receptor (LHR) activation on reproductive development, we have generated transgenic mice expressing a genetically engineered, constitutively active yoked hormone–receptor complex (YHR), in which a fusion protein of human chorionic gonadotropin (hCG) is covalently linked to the N-terminus of rat LHR. YHR-expressing mice (YHR+) were analyzed at pre- and post-pubertal ages. Relative to wild type (WT) controls, male mice exhibited prepubertal increases in testosterone levels and seminal vesicle weights, and decreases in serum FSH, serum LH, testes weight, and the size of the seminiferous tubules. In adult male YHR+ mice, testosterone and LH levels are not significantly different from WT controls. However, FSH levels and testes weights remain decreased. Female YHR+ mice undergo precocious puberty with early vaginal opening, accelerated uterine development, enhanced follicular development, including the presence of corpora lutea, and an increase in serum progesterone. At 12 weeks of age, the ovary exhibits a relative increase in the amount of interstitial tissue, comprised of cells that are hypertrophic and luteinized, as well as follicles that are degenerating. Additionally, hemorrhagic cysts develop in approximately 25% of the transgenic mice. These degenerative changes are consistent with an aging ovary suggesting that CG-induced LHR activation in female mice leads to precocious sexual development and ovarian lesions. Taken together, these data indicate that the single chain YHR is functional in vivo and demonstrate that YHR+ mice provide a novel system to further understand the reproductive consequences of aberrant LHR activation.
This article has been cited by other articles:
|
|
 |
|
  G. P. Finkielstain, P. Forcinito, J. C. K. Lui, K. M. Barnes, R. Marino, S. Makaroun, V. Nguyen, J. E. Lazarus, O. Nilsson, and J. Baron An Extensive Genetic Program Occurring during Postnatal Growth in Multiple Tissues Endocrinology, April 1, 2009; 150(4): 1791 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws Ovarian follicle development and transgenic mouse models Hum. Reprod. Update, September 1, 2006; 12(5): 537 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B Rulli and I. Huhtaniemi What have gonadotrophin overexpressing transgenic mice taught us about gonadal function? Reproduction, September 1, 2005; 130(3): 283 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T R. Kumar What have we learned about gonadotropin function from gonadotropin subunit and receptor knockout mice? Reproduction, September 1, 2005; 130(3): 293 - 302. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
