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Department of Human Anatomy and Genetics, University of Oxford (M.H.A., A.N.W., V.W., H.M.C.), Oxford, United Kingdom OX1 3QX; Department of Physiology, Institute of Biomedicine, University of Turku (I.H.), 20502 Turku, Finland; and School of Animal and Microbial Sciences, University of Reading (P.G.K.), Whiteknights, Reading, United Kingdom RG6 6AJ
Address all correspondence and requests for reprints to: Dr. Margaret H. Abel, Department of Human Anatomy and Genetics, University of Oxford, Oxford, United Kingdom OX1 3QX. E-mail: margaret.abel{at}anat.ox.ac.uk
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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-subunit
of LH and FSH (3) results in hypogonadism. In the recently described
FSHß knockout mouse, although females are infertile, male mice,
despite a significant reduction in testis size are fertile (4). Besides
ablation of pituitary gonadotropin cells or more specific gene
targeting of individual hormones, an alternative approach is to target
the receptor genes that are specific to each hormone and responsible
for signal transduction after hormone receptor binding. The actions of
FSH are mediated through a transmembrane receptor found on follicular
granulosa (5) and testicular Sertoli cells (6). In normal mice, FSH
binding activates its receptor and initiates the cascade of events
leading to downstream gene activation (7). We have taken the approach
of disrupting the gene encoding the receptor for FSH to produce FSH
receptor-deficient mice to investigate the specific role of FSH in
gonadal development and function. During the course of this study a
separate FSH receptor knockout (FSHRKO) was reported by Dierich
et al. (8). In characterizing our mutants we have found
several instances in which our observations differ from those of
Dierich et al. (8). We have also extended the analysis of
the mutants to include pituitary gonadotropin hormone content as well
as serum levels. At the gonadal level we have assayed the biologically
important dimeric inhibin peptides. In addition, we have compared
several aspects of FSHRKO mouse reproductive function with those of the
GnRH deficient hypogonadal (hpg) mouse. |
Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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. Linearized
targeting vector (12.3 kb; 50 µg) was electroporated into the 129 R1
ES cells (7 x 106) at 240 V and 500 µF,
and clones were selected in medium containing G418 (300 µg/ml;
Promega Corp., Madison, WI) and gancyclovir (2
µM; Roche, Indianapolis, IN). DNA from ES
cell clones was analyzed by Southern blot analysis; a single clone out
of 800 analyzed proved to have the mutant allele. This clone was
injected into C57BL6 blastocysts to generate chimeric mice. Germline
transmission was obtained from a single chimeric male mated with a
C57BL6 female. All animal procedures were carried out under Home Office
license.
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Tissue collection
For the analysis of gonadotropin hormone, pituitaries were
dissected out, weighed, and immediately frozen for assay. For the
analysis of gonadal inhibin A and B content, both gonads were dissected
out, weighed, and frozen. Blood was collected from the jugular sinus,
and serum was separated and frozen for assay.
Hormone assays
Serum and pituitary levels of FSH and LH were measured using
in-house immunofluorometric assays (Delfia, Wallac, Inc.,
Turku, Finland) as previously described (10, 11). A new pair of
antibodies was used in the FSH assay: a monoclonal against recombinant
human FSHß (FSH56A) and a polyclonal against recombinant human FSH
(R93–2705), both donated by Organon (Oss, The
Netherlands).
Serum and gonadal inhibin A concentrations were measured using a previously reported two-site enyzme-linked immunosorbent assay (12, 13). The detection limit was 2 pg recombinant human inhibin A/ml, and within- and between-plate coefficients of variation were 3.5% and 9.2%, respectively. Inhibin B was measured using a previously described two-site enyzme-linked immunosorbent assay (14, 15) with a sensitivity of 30 ng recombinant inhibin B/ml and intra- and interassay coefficients of variation of 4.2% and 9.8%, respectively.
Hormone treatment
Gonadotropin. The ability of the FSHRKO female mice to
respond to exogenous gonadotropin hormone was tested by injection of
PMSG (4 IU/mouse, sc) twice daily for 4 days, a regimen previously
shown to stimulate full follicular development in hpg female
mice (16). A control group of hpg females was included.
Animals were killed 12 h after the last injection, and ovaries and
uteri were removed, fixed for histological examination (see above), and
weighed.
Steroid. The very high levels of FSH and LH detected in the serum of the FSHRKO females (see below) prompted us to assess the ability of these mice to respond to estrogen. Two-centimeter SILASTIC brand implants (Dow Corning Corp., Midland, MI; id, 0.078 in.) containing 17ß-estradiol (E-8875, Sigma, St. Louis, MO) were placed sc. To control for the fact that estrogen could also have an effect at the ovarian level, one group of FSHKO females was ovariectomized before estrogen implantation. We also ovariectomized a group of FSHRKO females to determine whether this would have any effect on gonadotropin hormone synthesis and secretion.
Statistical analysis
Means were compared by one-way ANOVA or the general factorial
method (general linear model), where more than one variable was
analyzed and reported as the mean ± SEM. Differences
where P < 0.05 were considered statistically
significant.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Phenotype
Female mice homozygous for the FSH receptor mutation were
infertile. When caged with males of proven fertility over a period of 6
months, no young were born. On external examination of these females,
the vagina was seen to be imperforate. There was no evidence of estrous
cyclicity. Indeed, we can routinely identify mutant females from their
normal and heterozygous littermates by examination of the vagina (Fig. 2). Ovarian weight in 8-week-old FSHRKO
females was significantly reduced compared with those in normal and
heterozygous littermates (1.25 ± 0.15 vs. 3.62 ±
0.52 and 2.64 ± 0.21 mg respectively; P < 0.01).
The uteri were extremely thin (see Fig. 3a), with a mean weight of
5.9 ± 1.9 mg (n = 8), compared with normal and heterozygous
littermates, in which uterine weights were 83.3 ± 21.4 mg (n
= 6) and 66.3 ± 8.7 mg (n = 7), respectively.
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), 42.2 ± 8.0, 89.9 ± 21.1, 84.8 ± 24.8
mg, respectively Seminal vesicle weights did not differ among the
groups (FSHRKO, 123.9 ± 28.6; normal, 102.1 ± 45.6;
heterozygotes, 89.3 ± 17.1; n = 7, 6, and 7,
respectively).
Gonadal histology
Females. Follicles of all stages up to the preantral stage
were observed in the ovaries of FSHRKO mice. There was no evidence of
antral follicles or corpora lutea (Fig. 4, A and B). However, the ovaries
of FSHRKO mice were significantly heavier than those of GnRH-deficient
hpg mice, in which pituitary LH and FSH content was
drastically reduced (Fig. 4E). The major histological difference
between the ovaries of the hpg and FSHRKO mice was the appearance of
the stromal tissue. This was relatively hypertrophied in the FSHRKO
mice, with the interstitial cells containing large numbers of lipid
droplets (Fig. 4, C and D).
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, A and
B). All stages of spermatogenesis were observed, and in semithin
sections there was no obvious difference in Leydig cell morphology
(Fig. 5, C and D). Comparative analysis of the numbers of Leydig
and Sertoli cells in FSHRKO and normal mice must await a full
stereological study.
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), and the pituitary content of LH did
not differ from that seen in normal females. However, mean serum levels
of LH were 28-fold higher in the mutants (Fig. 6).
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).
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, A and B).
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). Serum levels of inhibins A and B were
not detectable in either normal or mutant males within the limits of
the assay (<8 and <60 pg/ml, respectively).
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), and there was no stimulation of
the uterus. In contrast, in hpg females ovarian weight
increased 4-fold (0.4 ± 0.1 to 1.8 ± 0.4 mg;
P < 0.05), and uterine weight increased 5-fold
(6.2 ± 0.6 to 34.9 ± 3.2 mg; P < 0.01;
n = 5). Graafian follicles were present in all PMSG-treated
hpg ovaries (Fig. 4G).
Steroid. Ovariectomy of FSHRKO females had no
significant effect on serum levels or pituitary content of either
gonadotropic hormone (Fig. 8). Treatment
of both intact FSHRKO and ovariectomized FSHRKO females with
17ß-estradiol for 1 week, significantly reduced serum LH to
levels seen in normal females (see Fig. 6). Serum FSH levels were
reduced by 50%, but remained significantly higher than levels in
normal females (42.7 ± 3.3 and 38.6 ± 2.2 vs.
5.9 ± 1.0 ng/ml; n = 4, 4, and 6; P <
0.01). The pituitary content of both LH and FSH was significantly
increased (P < 0.01 and P < 0.05,
respectively) after estrogen treatment in both groups of FSHRKO
females, and there was no difference between these two groups of
estrogen-treated mutant females.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The high circulating levels of both FSH and LH in the FSHRKO
female provides evidence of a failure of negative feedback from the
ovaries. The lack of production of biologically active estrogen is
evidenced by the atrophic uteri and imperforate vaginas. We have
provided direct evidence that levels of the biologically active inhibin
peptides A and B are undetectable in both ovary and serum. In contrast,
Dierich et al. (8) measured immunoreactive inhibin
-subunit and found no difference in serum levels between their
knockout and normal females. It is known that the ovary expresses a
large excess of -subunit over ß-subunit, and therefore measurement
of -subunit alone does not indicate the levels of dimeric inhibin
present and does not provide information on the levels of the
biologically active form of the peptide (18, 19). Disruption of the FSH
receptor is associated with alterations in pituitary gonadotropin
dynamics with an increased pituitary content of FSH, but not LH, in the
FSHRKO female compared with that in normal littermates and increased
serum levels of both hormones in the mutants. This difference must
reflect the failure of follicular growth and lack of production of
estrogen (20) and inhibin (21, 22). The observations that estrogen
treatment in intact and ovariectomized FSHRKO females reduced serum LH
levels to the normal range but only decreased FSH by 50% and that
these reductions in serum hormone levels were associated with an
increased pituitary content of both gonadotropins indicate that
estrogen is a major ovarian regulator of LH synthesis, storage, and
secretion and also has a role in FSH regulation. However, additional
factors, with dimeric inhibins the most likely candidates, are involved
in the control of FSH production. The physiological events that lead to
the differences in LH and FSH within the pituitary of the FSHRKO
females are likely to be complex; however, they do not appear to result
in any significant increase in pituitary weight compared with that in
normal mice at 8 weeks of age.
The fact that both FSHßKO and FSHRKO males are fertile demonstrates that neither FSH itself nor signaling via its receptor is essential for fertility in male mice. Nevertheless, testis weight and tubule diameter are half those in normal mice. This in all probability reflects a failure of FSH stimulation of Sertoli cell division during the perinatal period (23). In the GnRH-deficient hpg mouse in which circulating levels of LH and FSH are undetectable, Singh and Handelsman (24) reported that Sertoli cell numbers are only 40% of those in normal mice. Injections of recombinant FSH during the perinatal period significantly increased the number of Sertoli cell in hpg mice (24). Despite the lack of FSH signaling to the Sertoli cells in the FSHRKO mouse, LH stimulation of Leydig cells and androgen production is evident from the stimulation of seminal vesicle growth and, indeed, mating behavior in the FSHRKO males. The importance of testosterone in the stimulation of spermatogenesis has been shown by the fact that a testosterone implant alone can stimulate all stages of spermatogenesis in hpg mice (25). Therefore, in the FSHRKO and the FSHßKO mice, the fertility of the males can be accounted for by testosterone alone despite the fact that Dierich et al. (8) reported an approximately 50% reduction in circulating levels of testosterone in their knockout males. Both Dierich (8) and Kumar (4) found evidence of reduced sperm numbers and aberrant sperm morphology in their mutants, suggesting the possibility that FSH in the adult may still be important for normal spermiogenesis. Another possibility is that the reduced numbers of Sertoli cells may be unable to support the numbers of germ cells developing under the stimulation of testosterone (26). However, any sperm abnormalities in our mice were not sufficient to compromise fertilization or litter size in our FSHRKO colony, an additional difference from the findings of Dierich et al. (8), where litter size was reduced by 35–50% in heterozygous compared with that of wild-type matings. A full analysis of intratesticular cellular dynamics will be necessary to address this problem.
Inhibin B, rather than inhibin A, has been considered to provide negative feedback upon pituitary FSH in the male (27). Whether this forms part of a classical feedback loop in which elevated FSH stimulates inhibin is uncertain, although administration of FSH can stimulate testicular inhibin production (28). In our mice that cannot respond to FSH, intratesticular levels of dimeric inhibins A and B are detectable at concentrations not significantly different from those in normal littermates. Evidence is accumulating that the production of inhibin within the testis is dependant upon specific germ cell-Sertoli interactions (29, 30, 31). In our mice all stages of spermatogenesis are present without any input from FSH; therefore, these interactions are likely to be occurring despite the absence of FSH. Exactly what contribution intratesticular inhibin has in normal spermatogenesis remains to be determined. What is certain is that in the absence of inhibin, the program of cellular division and differentiation is disturbed, and tumors develop (32). As expected, the testicular inhibin B content was considerably greater than the inhibin A content in both normal and mutant mice. Despite this, we were unable to quantify serum inhibin levels in either group due to the small volume of serum available coupled with the fact that the inhibin B assay is intrinsically less sensitive than the inhibin A assay. We are therefore unable to correlate serum FSH with dimeric inhibin in our mutants. The increased secretion of LH in FSHRKO male mice may be explained by the reduced circulating testosterone (8), which, although sufficient for stimulation of behavior and accessory sexual tissue, may not be able to exert full negative feedback on the pituitary.
Preliminary identification and isolation of the pituitary gonadotropins were performed over 50 yr ago (33). Disruption of individual gonadotropin genes or the genes encoding their specific receptors has extended this work and enabled the role of each hormone to be more precisely documented. In this paper describing our FSHRKO mice we have identified a number of differences from the model described by Dierich et al. (8) and have added further observations on pituitary hormone synthesis and secretion and gonadal morphology and physiology. An investigation into the definitive effects of FSH alone on gonadal physiology must await the production of either the LHß- or the LH receptor-deficient mouse.
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Acknowledgments |
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Footnotes |
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Received September 8, 1999.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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-subunit produces hypogonadal and hypothyroid mice. Genes Dev 9:2007–2019-ßA dimer) and
total inhibin in the peripheral circulation and ovaries of rats
after gonadotrophin-induced follicular development and during the
normal oestrous cycle. J Endocrinol 147:271–283-Inhibin is a tumor-suppressor gene with gonadal
specificity in mice. Nature 360:313–319[CrossRef][Medline]
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B. P. Hermann and L. L. Heckert Silencing of Fshr Occurs through a Conserved, Hypersensitive Site in the First Intron Mol. Endocrinol., August 1, 2005; 19(8): 2112 - 2131. [Abstract] [Full Text] [PDF]
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C. J. Guigon, N. Coudouel, S. Mazaud-Guittot, M. G. Forest, and S. Magre Follicular Cells Acquire Sertoli Cell Characteristics after Oocyte Loss Endocrinology, July 1, 2005; 146(7): 2992 - 3004. [Abstract] [Full Text] [PDF]
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J. Chaudhary, I. Sadler-Riggleman, J. M. Ague, and M. K. Skinner The Helix-Loop-Helix Inhibitor of Differentiation (ID) Proteins Induce Post-Mitotic Terminally Differentiated Sertoli Cells to Re-Enter the Cell Cycle and Proliferate Biol Reprod, May 1, 2005; 72(5): 1205 - 1217. [Abstract] [Full Text] [PDF]
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R. S. McRae, H. M. Johnston, M. Mihm, and P. J. O'Shaughnessy Changes in Mouse Granulosa Cell Gene Expression during Early Luteinization Endocrinology, January 1, 2005; 146(1): 309 - 317. [Abstract] [Full Text] [PDF]
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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]
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 X. Ma, Y. Dong, M. M. Matzuk, and T. R. Kumar Targeted disruption of luteinizing hormone {beta}-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility PNAS, December 7, 2004; 101(49): 17294 - 17299. [Abstract] [Full Text] [PDF]
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M Vigier, M Weiss, M H Perrard, M Godet, and P Durand The effects of FSH and of testosterone on the completion of meiosis and the very early steps of spermiogenesis of the rat: an in vitro study J. Mol. Endocrinol., December 1, 2004; 33(3): 729 - 742. [Abstract] [Full Text] [PDF]
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T. Sato, Y. Kanai, T. Noma, M. Kanai-Azuma, S. Taya, T. Matsui, M. Ishii, H. Kawakami, M. Kurohmaru, K. Kaibuchi, et al. A close correlation in the expression patterns of Af-6 and Usp9x in Sertoli and granulosa cells of mouse testis and ovary Reproduction, November 1, 2004; 128(5): 583 - 594. [Abstract] [Full Text] [PDF]
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R. C Hirst, M. H Abel, V. Wilkins, C. Simpson, P. G Knight, F.-P. Zhang, I. Huhtaniemi, T R. Kumar, and H. M Charlton Influence of mutations affecting gonadotropin production or responsiveness on expression of inhibin subunit mRNA and protein in the mouse ovary Reproduction, July 1, 2004; 128(1): 43 - 52. [Abstract] [Full Text] [PDF]
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 H. Alam, E. T. Maizels, Y. Park, S. Ghaey, Z. J. Feiger, N. S. Chandel, and M. Hunzicker-Dunn Follicle-stimulating Hormone Activation of Hypoxia-inducible Factor-1 by the Phosphatidylinositol 3-Kinase/AKT/Ras Homolog Enriched in Brain (Rheb)/Mammalian Target of Rapamycin (mTOR) Pathway Is Necessary for Induction of Select Protein Markers of Follicular Differentiation J. Biol. Chem., May 7, 2004; 279(19): 19431 - 19440. [Abstract] [Full Text] [PDF]
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J. D. Hennebold Characterization of the ovarian transcriptome through the use of differential analysis of gene expression methodologies Hum. Reprod. Update, May 1, 2004; 10(3): 227 - 239. [Abstract] [Full Text] [PDF]
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F.-C. Ke, L.-C. Chuang, M.-T. Lee, Y. J. Chen, S.-W. Lin, P. S. Wang, D. M. Stocco, and J.-J. Hwang The Modulatory Role of Transforming Growth Factor {beta}1 and Androstenedione on Follicle-Stimulating Hormone-Induced Gelatinase Secretion and Steroidogenesis in Rat Granulosa Cells Biol Reprod, May 1, 2004; 70(5): 1292 - 1298. [Abstract] [Full Text] [PDF]
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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]
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H. Johnston, P. J. Baker, M. Abel, H. M. Charlton, G. Jackson, L. Fleming, T. R. Kumar, and P. J. O'Shaughnessy Regulation of Sertoli Cell Number and Activity by Follicle-Stimulating Hormone and Androgen during Postnatal Development in the Mouse Endocrinology, January 1, 2004; 145(1): 318 - 329. [Abstract] [Full Text] [PDF]
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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]
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K. H. Burns, G. E. Owens, S. C. Ogbonna, J. H. Nilson, and M. M. Matzuk Expression Profiling Analyses of Gonadotropin Responses and Tumor Development in the Absence of Inhibins Endocrinology, October 1, 2003; 144(10): 4492 - 4507. [Abstract] [Full Text] [PDF]
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A. S. Calikoglu Adrenocorticotropic Hormone, a New Player in the Control of Testicular Steroidogenesis Endocrinology, August 1, 2003; 144(8): 3277 - 3278. [Full Text] [PDF]
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P. Kezele and M. K. Skinner Regulation of Ovarian Primordial Follicle Assembly and Development by Estrogen and Progesterone: Endocrine Model of Follicle Assembly Endocrinology, August 1, 2003; 144(8): 3329 - 3337. [Abstract] [Full Text] [PDF]
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M. M. Matzuk, F. J. DeMayo, L. A. Hadsell, and T. R. Kumar Overexpression of Human Chorionic Gonadotropin Causes Multiple Reproductive Defects in Transgenic Mice Biol Reprod, July 1, 2003; 69(1): 338 - 346. [Abstract] [Full Text] [PDF]
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S. Migrenne, C. Racine, F. Guillou, and R. Habert Pituitary Hormones Inhibit the Function and Differentiation of Fetal Sertoli Cells Endocrinology, June 1, 2003; 144(6): 2617 - 2622. [Abstract] [Full Text] [PDF]
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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]
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 L. A. Allen, J. C. Achermann, P. Pakarinen, T. J. Kotlar, I. T. Huhtaniemi, J. L. Jameson, T. D. Cheetham, and S. G. Ball A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics Hum. Reprod., February 1, 2003; 18(2): 251 - 256. [Abstract] [Full Text] [PDF]
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P. J. Baker, P. Pakarinen, I. T. Huhtaniemi, M. H. Abel, H. M. Charlton, T. R. Kumar, and P. J. O'Shaughnessy Failure of Normal Leydig Cell Development in Follicle-Stimulating Hormone (FSH) Receptor-Deficient Mice, But Not FSH{beta}-Deficient Mice: Role for Constitutive FSH Receptor Activity Endocrinology, January 1, 2003; 144(1): 138 - 145. [Abstract] [Full Text] [PDF]
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R. A. Anderson and D. T. Baird Male Contraception Endocr. Rev., December 1, 2002; 23(6): 735 - 762. [Abstract] [Full Text] [PDF]
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P. Pakarinen, S. Kimura, F. El-Gehani, L. J. Pelliniemi, and I. Huhtaniemi Pituitary Hormones Are Not Required for Sexual Differentiation of Male Mice: Phenotype of the T/ebp/Nkx2.1 Null Mutant Mice Endocrinology, November 1, 2002; 143(11): 4477 - 4482. [Abstract] [Full Text] [PDF]
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B. J. Arey, D. C. Deecher, E. S. Shen, P. E. Stevis, E. H. Meade Jr, J. Wrobel, D. E. Frail, and F. J. Lopez Identification and Characterization of a Selective, Nonpeptide Follicle-Stimulating Hormone Receptor Antagonist Endocrinology, October 1, 2002; 143(10): 3822 - 3829. [Abstract] [Full Text] [PDF]
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K. H. Burns and M. M. Matzuk Minireview: Genetic Models for the Study of Gonadotropin Actions Endocrinology, August 1, 2002; 143(8): 2823 - 2835. [Abstract] [Full Text] [PDF]
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W. Xing and M. R. Sairam Retinoic Acid Mediates Transcriptional Repression of Ovine Follicle-Stimulating Hormone Receptor Gene via a Pleiotropic Nuclear Receptor Response Element Biol Reprod, July 1, 2002; 67(1): 204 - 211. [Abstract] [Full Text] [PDF]
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W. Yan, A. Rajkovic, M. M. Viveiros, K. H. Burns, J. J. Eppig, and M. M. Matzuk Identification of Gasz, an Evolutionarily Conserved Gene Expressed Exclusively in Germ Cells and Encoding a Protein with Four Ankyrin Repeats, a Sterile-{alpha} Motif, and a Basic Leucine Zipper Mol. Endocrinol., June 1, 2002; 16(6): 1168 - 1184. [Abstract] [Full Text] [PDF]
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 S. Ohtsuka, S. Takaki, M. Iseki, K. Miyoshi, N. Nakagata, Y. Kataoka, N. Yoshida, K. Takatsu, and A. Yoshimura SH2-B Is Required for Both Male and Female Reproduction Mol. Cell. Biol., May 1, 2002; 22(9): 3066 - 3077. [Abstract] [Full Text] [PDF]
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C. Romero, A. Paredes, G. A. Dissen, and S. R. Ojeda Nerve Growth Factor Induces the Expression of Functional FSH Receptors in Newly Formed Follicles of the Rat Ovary Endocrinology, April 1, 2002; 143(4): 1485 - 1494. [Abstract] [Full Text] [PDF]
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J. S. Richards, S. C. Sharma, A. E. Falender, and Y. H. Lo Expression of FKHR, FKHRL1, and AFX Genes in the Rodent Ovary: Evidence for Regulation by IGF-I, Estrogen, and the Gonadotropins Mol. Endocrinol., March 1, 2002; 16(3): 580 - 599. [Abstract] [Full Text] [PDF]
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 L. L. Heckert and M. D. Griswold The Expression of the Follicle-stimulating Hormone Receptor in Spermatogenesis Recent Prog. Horm. Res., January 1, 2002; 57(1): 129 - 148. [Abstract] [Full Text] [PDF]
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W. Xing and M. R. Sairam Role of CACC-Box in the Regulation of Ovine Follicle-Stimulating Hormone Receptor Expression Biol Reprod, October 1, 2001; 65(4): 1142 - 1149. [Abstract] [Full Text] [PDF]
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N. Danilovich, I. Roy, and M. R. Sairam Ovarian Pathology and High Incidence of Sex Cord Tumors in Follitropin Receptor Knockout (FORKO) Mice Endocrinology, August 1, 2001; 142(8): 3673 - 3684. [Abstract] [Full Text] [PDF]
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S. B. Seminara and W. F. Crowley Jr. Perspective: The Importance of Genetic Defects in Humans in Elucidating the Complexities of the Hypothalamic-Pituitary-Gonadal Axis Endocrinology, June 1, 2001; 142(6): 2173 - 2177. [Full Text] [PDF]
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I. Huhtaniemi and A. Bartke Perspective: Male Reproduction Endocrinology, June 1, 2001; 142(6): 2178 - 2183. [Full Text] [PDF]
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J. S. Richards Perspective: The Ovarian Follicle--A Perspective in 2001 Endocrinology, June 1, 2001; 142(6): 2184 - 2193. [Full Text] [PDF]
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C. M. Allan, M. Haywood, S. Swaraj, J. Spaliviero, A. Koch, M. Jimenez, M. Poutanen, J. Levallet, I. Huhtaniemi, P. Illingworth, et al. A Novel Transgenic Model to Characterize the Specific Effects of Follicle-Stimulating Hormone on Gonadal Physiology in the Absence of Luteinizing Hormone Actions Endocrinology, June 1, 2001; 142(6): 2213 - 2220. [Abstract] [Full Text] [PDF]
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K. F. Roby Alterations in Follicle Development, Steroidogenesis, and Gonadotropin Receptor Binding in a Model of Ovulatory Blockade Endocrinology, June 1, 2001; 142(6): 2328 - 2335. [Abstract] [Full Text] [PDF]
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J. Levallet, P. Koskimies, N. Rahman, and I. Huhtaniemi The Promoter of Murine Follicle-Stimulating Hormone Receptor: Functional Characterization and Regulation by Transcription Factor Steroidogenic Factor 1 Mol. Endocrinol., January 1, 2001; 15(1): 80 - 92. [Abstract] [Full Text]
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F.-P. Zhang, M. Poutanen, J. Wilbertz, and I. Huhtaniemi Normal Prenatal but Arrested Postnatal Sexual Development of Luteinizing Hormone Receptor Knockout (LuRKO) Mice Mol. Endocrinol., January 1, 2001; 15(1): 172 - 183. [Abstract] [Full Text]
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Z. M. Lei, S. Mishra, W. Zou, B. Xu, M. Foltz, X. Li, and Ch. V. Rao Targeted Disruption of Luteinizing Hormone/Human Chorionic Gonadotropin Receptor Gene Mol. Endocrinol., January 1, 2001; 15(1): 184 - 200. [Abstract] [Full Text]
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 L Zhao, M Bakke, Y Krimkevich, L. Cushman, A. Parlow, S. Camper, and K. Parker Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function Development, January 1, 2001; 128(2): 147 - 154. [Abstract] [PDF]
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10 µg) isolated from the
tails of 1 litter was digested, extracted with phenol/chloroform,
digested with EcoRI, electrophoresed, transferred to
nylon membrane, and hybridized with the 1.7-kb XbaI
fragment, 5' of the insertion. A single 8-kb band indicates a
homozygous mutant phenotype (-/-). Genotype analysis of offspring
from F1 matings followed the normal Mendelian distribution
of 1:2:1. X, XbaI; Sc, ScaI; Sm, SmaI;
E, EcoRT; and E1, exon one.
