| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Department of Pharmacology, Case Western Reserve University School of Medicine (K.A.R., J.H.N.), Cleveland, Ohio 44106; and the Department of Anatomy, University of Maryland School of Medicine (A.N.H.), Baltimore, Maryland 21201
Address all correspondence and requests for reprints to: John H. Nilson, Ph.D., Department of Pharmacology, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, Ohio 44106-4975. E-mail: JHN{at}PO.CWRU.EDU
In women, chronically elevated androgens have been associated with polycystic ovarian syndrome and infertility. Recently, we described transgenic mice with elevated serum LH secondary to targeted expression of a transgene encoding a chimeric LH ß-subunit. Mature transgenic females exhibit elevated androgens, anovulation, and a range of ovarian phenotypes including cysts, widespread luteinization, and tumors. In the present study we have examined serum levels of LH and testosterone and the concurrent development of the reproductive system in prepubertal mice. Serum LH in prepubertal females was elevated despite increased serum testosterone and estradiol, indicating a relative insensitivity to steroid negative feedback. Elevated serum LH and hyperandrogenemia resulted in accelerated vaginal opening and ovarian follicular development in transgenic females. Precocious antral follicle formation and conspicuous hypertrophy of the theca-interstitium preceded the development of large cysts with marked hemorrhage. Based on these studies we conclude that chronic prepubertal elevation of serum LH results in gonadotropin-dependent hyperandrogenemia, leading to abnormal sexual development and significant ovarian pathology.
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 J. F. Couse, M. M. Yates, K. F. Rodriguez, J. A. Johnson, D. Poirier, and K. S. Korach The Intraovarian Actions of Estrogen Receptor-{alpha} Are Necessary to Repress the Formation of Morphological and Functional Leydig-Like Cells in the Female Gonad Endocrinology, August 1, 2006; 147(8): 3666 - 3678. [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. 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]
|
|
|
|
 |
|
 G. Piaditis, A. Angellou, G. Kontogeorgos, N. Mazarakis, T. Kounadi, G. Kaltsas, K. Vamvakidis, R. V. Lloyd, E. Horvath, and K. Kovacs Ectopic Bioactive Luteinizing Hormone Secretion by a Pancreatic Endocrine Tumor, Manifested as Luteinized Granulosa-Thecal Cell Tumor of the Ovaries J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2097 - 2103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Soderlund, P. Canto, S. Carranza-Lira, and J.P. Mendez No evidence of mutations in the P450 aromatase gene in patients with polycystic ovary syndrome Hum. Reprod., April 1, 2005; 20(4): 965 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 H. P. Mohammad, D. D. Seachrist, C. C. Quirk, and J. H. Nilson Reexpression of p8 Contributes to Tumorigenic Properties of Pituitary Cells and Appears in a Subset of Prolactinomas in Transgenic Mice that Hypersecrete Luteinizing Hormone Mol. Endocrinol., October 1, 2004; 18(10): 2583 - 2593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Couse, M. M. Yates, R. Sanford, A. Nyska, J. H. Nilson, and K. S. Korach Formation of Cystic Ovarian Follicles Associated with Elevated Luteinizing Hormone Requires Estrogen Receptor-{beta} Endocrinology, October 1, 2004; 145(10): 4693 - 4702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Capen Mechanisms of Hormone-Mediated Carcinogenesis of the Ovary Toxicol Pathol, February 1, 2004; 32(2_suppl): 1 - 5. [Abstract] [PDF]
|
|
|
|
|
|
A. Belgorosky, C. Pepe, R. Marino, G. Guercio, N. Saraco, E. Vaiani, and M. A. Rivarola Hypothalamic-Pituitary-Ovarian Axis during Infancy, Early and Late Prepuberty in an Aromatase-Deficient Girl Who Is a Compound Heterocygote for Two New Point Mutations of the CYP19 Gene J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5127 - 5131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Mohammad, R. A. Abbud, A. F. Parlow, J. S. Lewin, and J. H. Nilson Targeted Overexpression of Luteinizing Hormone Causes Ovary-Dependent Functional Adenomas Restricted to Cells of the Pit-1 Lineage Endocrinology, October 1, 2003; 144(10): 4626 - 4636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Kero, E. Savontaus, M. Mikola, U. Pesonen, M. Koulu, R. A. Keri, J. H. Nilson, M. Poutanen, and I. T. Huhtaniemi Obesity in transgenic female mice with constitutively elevated luteinizing hormone secretion Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E812 - E818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
S. Paruthiyil, M. E. Majdoubi, M. Conti, and R. I. Weiner Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats PNAS, December 24, 2002; 99(26): 17191 - 17196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Rulli, A. Kuorelahti, O. Karaer, L. J. Pelliniemi, M. Poutanen, and I. Huhtaniemi Reproductive Disturbances, Pituitary Lactotrope Adenomas, and Mammary Gland Tumors in Transgenic Female Mice Producing High Levels of Human Chorionic Gonadotropin Endocrinology, October 1, 2002; 143(10): 4084 - 4095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Milliken, R. K. Ameduri, M. D. Landis, A. Behrooz, F. W. Abdul-Karim, and R. A. Keri Ovarian Hyperstimulation by LH Leads to Mammary Gland Hyperplasia and Cancer Predisposition in Transgenic Mice Endocrinology, September 1, 2002; 143(9): 3671 - 3680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
G. E. Owens, R. A. Keri, and J. H. Nilson Ovulatory Surges of Human CG Prevent Hormone-Induced Granulosa Cell Tumor Formation Leading to the Identification of Tumor-Associated Changes in the Transcriptome Mol. Endocrinol., June 1, 2002; 16(6): 1230 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.A. Hodges, A. Ilagan, D. Jennings, R. Keri, J. Nilson, and P.A. Hunt Experimental evidence that changes in oocyte growth influence meiotic chromosome segregation Hum. Reprod., May 1, 2002; 17(5): 1171 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. McMullen, B.-N. Cho, C. J. Yates, and K. E. Mayo Gonadal Pathologies in Transgenic Mice Expressing the Rat Inhibin {alpha}-Subunit Endocrinology, November 1, 2001; 142(11): 5005 - 5014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Long, I. R. Cohen, C. L. Gries, J. K. Young, P. C. Francis, and C. C. Capen Proliferative Lesions of Ovarian Granulosa Cells and Reversible Hormonal Changes Induced in Rats by a Selective Estrogen Receptor Modulator Toxicol Pathol, October 1, 2001; 29(6): 719 - 726. [Abstract] [PDF]
|
|
|
|
 |
|
 S. F. Palter, A. B. Tavares, A. Hourvitz, J. D. Veldhuis, and E. Y. Adashi Are Estrogens of Import to Primate/Human Ovarian Folliculogenesis? Endocr. Rev., June 1, 2001; 22(3): 389 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Long, I. R. Cohen, C. L. Gries, J. K. Young, P. C. Francis, and C. C. Capen Proliferative Lesions of Ovarian Granulosa Cells and Reversible Hormonal Changes Induced in Rats by a Selective Estrogen Receptor Modulator Toxicol Pathol, June 1, 2001; 29(4): 403 - 410. [Abstract] [PDF]
|
|
|
|
|
|
J. S. Richards Perspective: The Ovarian Follicle--A Perspective in 2001 Endocrinology, June 1, 2001; 142(6): 2184 - 2193. [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Cushman, D. E. Watkins-Chow, M. L. Brinkmeier, L. T. Raetzman, A. L. Radak, R. V. Lloyd, and S. A. Camper Persistent Prop1 expression delays gonadotrope differentiation and enhances pituitary tumor susceptibility Hum. Mol. Genet., May 1, 2001; 10(11): 1141 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Lara, G. A. Dissen, V. Leyton, A. Paredes, H. Fuenzalida, J. L. Fiedler, and S. R. Ojeda An Increased Intraovarian Synthesis of Nerve Growth Factor and Its Low Affinity Receptor Is a Principal Component of Steroid-Induced Polycystic Ovary in the Rat Endocrinology, March 1, 2000; 141(3): 1059 - 1072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Rosenfeld, A. A. Murray, G. Simmer, M. G. Hufford, M. F. Smith, N. Spears, and D. B. Lubahn Gonadotropin Induction of Ovulation and Corpus Luteum Formation in Young Estrogen Receptor-{alpha} Knockout Mice Biol Reprod, March 1, 2000; 62(3): 599 - 605. [Abstract] [Full Text]
|
|
|
|
|
|
P. W. Speiser, M. Susin, H. Sasano, S. Bohrer, and J. Markowitz Ovarian Hyperthecosis in the Setting of Portal Hypertension J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 873 - 877. [Abstract] [Full Text]
|
|
|
|
 |
|
 S Dupont, A Krust, A Gansmuller, A Dierich, P Chambon, and M Mark Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes Development, January 10, 2000; 127(19): 4277 - 4291. [Abstract] [PDF]
|
|
|
|
|
|
R. A. Keri, K. L. Lozada, F. W. Abdul-Karim, J. H. Nadeau, and J. H. Nilson Luteinizing hormone induction of ovarian tumors: Oligogenic differences between mouse strains dictates tumor disposition PNAS, January 4, 2000; 97(1): 383 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Couse, D. O. Bunch, J. Lindzey, D. W. Schomberg, and K. S. Korach Prevention of the Polycystic Ovarian Phenotype and Characterization of Ovulatory Capacity in the Estrogen Receptor-{alpha} Knockout Mouse Endocrinology, December 1, 1999; 140(12): 5855 - 5865. [Abstract] [Full Text]
|
|
|
|
|
|
R. A. Abbud, R. K. Ameduri, J. S. Rao, T. M. Nett, and J. H. Nilson Chronic Hypersecretion of Luteinizing Hormone in Transgenic Mice Selectively Alters Responsiveness of the {alpha}-Subunit Gene to Gonadotropin-Releasing Hormone and Estrogens Mol. Endocrinol., September 1, 1999; 13(9): 1449 - 1459. [Abstract] [Full Text]
|
|
|
|
|
|
J. F. Couse and K. S. Korach Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us? Endocr. Rev., June 1, 1999; 20(3): 358 - 417. [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]
|
|
|
|
|
|
D. W. Schomberg, J. F. Couse, A. Mukherjee, D. B. Lubahn, M. Sar, K. E. Mayo, and K. S. Korach Targeted Disruption of the Estrogen Receptor-{alpha} Gene in Female Mice: Characterization of Ovarian Responses and Phenotype in the Adult Endocrinology, June 1, 1999; 140(6): 2733 - 2744. [Abstract] [Full Text]
|
|
|
|
|
|
R. L. Robker and J. S. Richards Hormone-Induced Proliferation and Differentiation of Granulosa Cells: A Coordinated Balance of the Cell Cycle Regulators Cyclin D2 and p27Kip1 Mol. Endocrinol., July 1, 1998; 12(7): 924 - 940. [Abstract] [Full Text]
|
|
|
|
|
|
E. W. C. M. Van Dam, F. Roelfsema, J. D. Veldhuis, F. M. Helmerhorst, M. Frolich, A. E. Meinders, H. M. J. Krans, and H. Pijl Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E865 - E872. [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 |
