| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
ANZAC Research Institute and Andrology Laboratory (C.M.A., M.H., S.S., J.S., A.K., M.J., D.J.H.), Department of Medicine, University of Sydney, New South Wales 2006, Australia; Department of Reproductive Medicine (P.I.), Westmead Hospital, University of Sydney, New South Wales 2145, Australia; and Department of Physiology (M.P., J.L., I.H.), University of Turku, 20520 Turku, Finland
Address all correspondence and requests for reprints to: Charles M. Allan, ANZAC Research Institute, Concord Hospital, Sydney, New South Wales 2139, Australia.
Gonadal function is wholly reliant on the two pituitary-derived
gonadotropins, FSH and LH. Identifying the specific effects of FSH has
been difficult because of the intimate relationship between LH and FSH
action and inherent limitations of classic research paradigms. We
describe a novel transgenic model to characterize the definitive
actions of FSH alone, distinct from LH effects, created by combining
transgenic FSH expression with the gonadotropin-deficient background of
the hypogonadal (hpg) mouse. A tandem transgene
construct encoding each 
- and ß-subunit of human FSH, under the
rat insulin II promoter, expressed biologically active heterodimers at
serum levels, by immunoassay, equivalent to circulating FSH
concentrations in fertile humans (0.1–25 IU/liter). Transgenic mice
were crossed into the hpg mouse genotype to obtain
LH-deficient animals secreting FSH alone. Testis weights of adult
FSHxhpg mice were increased up to 5-fold, relative to
nontransgenic hpg controls (P <
0.001). However, only transgenic males with serum FSH levels more than
1 IU/liter showed testis weights increased relative to
hpg controls, indicating a physiological FSH threshold
for the testicular response. Histology of enlarged
FSHxhpg testes revealed round spermatids and sparse
numbers of elongated spermatids, demonstrating that the
testosterone-independent FSH response targeting the Sertoli cell can
facilitate completion of meiosis and minimal initiation, but not
completion, of spermiogenesis. Transgenic FSH also induced inhibin B
secretion in FSHxhpg mice, but showed a distinct sexual
dimorphism with only females exhibiting a strong FSH dose-dependent
increase in serum inhibin B levels (r2 = 0.84). In
addition, ovaries of FSHxhpg females were enlarged up
to 10-fold (P < 0.001), characterized by increased
follicular recruitment and development to type 7 antral follicles.
Thus, these findings show that the transgenic FSHxhpg
mouse provides a unique model for detailed investigations of the
definitive in vivo actions of FSH alone.
This article has been cited by other articles:
 |
|
 |
|
  S. Mhaouty-Kodja, A. Lozach, R. Habert, M. Tanneux, C. Guigon, S. Brailly-Tabard, J.-P. Maltier, and C. Legrand-Maltier Fertility and spermatogenesis are altered in {alpha}1b-adrenergic receptor knockout male mice J. Endocrinol., November 1, 2007; 195(2): 281 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. McTavish, M. Jimenez, K. A. Walters, J. Spaliviero, N. P. Groome, A. P. Themmen, J. A. Visser, D. J. Handelsman, and C. M. Allan Rising Follicle-Stimulating Hormone Levels with Age Accelerate Female Reproductive Failure Endocrinology, September 1, 2007; 148(9): 4432 - 4439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Walters, C. M. Allan, M. Jimenez, P. R. Lim, R. A. Davey, J. D. Zajac, P. Illingworth, and D. J. Handelsman Female Mice Haploinsufficient for an Inactivated Androgen Receptor (AR) Exhibit Age-Dependent Defects That Resemble the AR Null Phenotype of Dysfunctional Late Follicle Development, Ovulation, and Fertility Endocrinology, August 1, 2007; 148(8): 3674 - 3684. [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]
|
|
|
|
 |
|
 C. M. Allan, A. Garcia, J. Spaliviero, M. Jimenez, and D. J. Handelsman Maintenance of Spermatogenesis by the Activated Human (Asp567Gly) FSH Receptor During Testicular Regression Due to Hormonal Withdrawal Biol Reprod, May 1, 2006; 74(5): 938 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C M Allan, Y Wang, M Jimenez, B Marshan, J Spaliviero, P Illingworth, and D J Handelsman Follicle-stimulating hormone increases primordial follicle reserve in mature female hypogonadal mice. J. Endocrinol., March 1, 2006; 188(3): 549 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Young, R. Salomon, W. Au, C. Allan, P. Russell, and Q. Dong Ornithine Decarboxylase (ODC) Expression Pattern in Human Prostate Tissues and ODC Transgenic Mice J. Histochem. Cytochem., February 1, 2006; 54(2): 223 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, H. Newton, J. A. Spaliviero, C. M. Allan, B. Marshan, D. J. Handelsman, and P. J. Illingworth Gonadotropin Control of Inhibin Secretion and the Relationship to Follicle Type and Number in the hpg Mouse Biol Reprod, October 1, 2005; 73(4): 610 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P Meehan, B. G Harmon, M. E Overcast, K. K Yu, S. A Camper, D. Puett, and P. Narayan Gonadal defects and hormonal alterations in transgenic mice expressing a single chain human chorionic gonadotropin-lutropin receptor complex J. Mol. Endocrinol., April 1, 2005; 34(2): 489 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jimenez, J.A. Spaliviero, A.J. Grootenhuis, J. Verhagen, C.M. Allan, and D.J. Handelsman Validation of an Ultrasensitive and Specific Immunofluorometric Assay for Mouse Follicle-Stimulating Hormone Biol Reprod, January 1, 2005; 72(1): 78 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Allan, A. Garcia, J. Spaliviero, F.-P. Zhang, M. Jimenez, I. Huhtaniemi, and D. J. Handelsman Complete Sertoli Cell Proliferation Induced by Follicle-Stimulating Hormone (FSH) Independently of Luteinizing Hormone Activity: Evidence from Genetic Models of Isolated FSH Action Endocrinology, April 1, 2004; 145(4): 1587 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Spaliviero, M. Jimenez, C. M. Allan, and D. J. Handelsman Luteinizing Hormone Receptor-Mediated Effects on Initiation of Spermatogenesis in Gonadotropin-Deficient (hpg) Mice Are Replicated by Testosterone Biol Reprod, January 1, 2004; 70(1): 32 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-P. Zhang, T. Pakarainen, M. Poutanen, J. Toppari, and I. Huhtaniemi The low gonadotropin-independent constitutive production of testicular testosterone is sufficient to maintain spermatogenesis PNAS, November 11, 2003; 100(23): 13692 - 13697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Haywood, J. Spaliviero, M. Jimemez, N. J. C. King, D. J. Handelsman, and C. M. Allan Sertoli and Germ Cell Development in Hypogonadal (hpg) Mice Expressing Transgenic Follicle-Stimulating Hormone Alone or in Combination with Testosterone Endocrinology, February 1, 2003; 144(2): 509 - 517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Anderson and D. T. Baird Male Contraception Endocr. Rev., December 1, 2002; 23(6): 735 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Haywood, N. Tymchenko, J. Spaliviero, A. Koch, M. Jimenez, J. Gromoll, M. Simoni, V. Nordhoff, D. J. Handelsman, and C. M. Allan An Activated Human Follicle-Stimulating Hormone (FSH) Receptor Stimulates FSH-Like Activity in Gonadotropin-Deficient Transgenic Mice Mol. Endocrinol., November 1, 2002; 16(11): 2582 - 2591. [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 |
