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Abstract:

The two gonadotrophins, follicle-stimulating hormone and luteinising hormone, are pivotal regulators of the development and maintenance of normal fertility by maintaining testicular and ovarian endocrine function and gametogenesis. Too low gonadotrophin secretion, i.e. hypogonadotrophic hypogonadism, is a common cause of infertility. But there are also physiological and pathophysiological conditions where gonadotrophin secretion and/or action are either transiently or chronically elevated, such as pregnancy, pituitary tumours, polycystic ovarian syndrome, activating gonadotrophin receptor mutations, perimenopause and menopause. These situations can be either the primary or secondary cause of infertility and gonadal pathologies in both sexes. Also the role of gonadotrophins as tumour promoters is possible. Recently, the possibility to combine information from genetically modified mice and human phenotypes in connection with mutations of gonadotrophin or gonadotrophin receptor genes has elucidated many less well known mechanisms involved in dysregulation of gonadotrophin function. Among the genetically modified mouse models, transgenic mice with gonadotrophin hypersecretion have been developed during the last few years. In this review, we describe the key findings on transgenic mouse models overexpressing gonadotrophins and present their possible implications in related human pathologies. In addition, we provide examples of genetic mouse models with secondary effects on gonadotrophin production and, consequently, on gonadal function. © 2005 Society for Reproduction and Fertility.

Registro:

Documento: Artículo
Título:What have gonadotrophin overexpressing transgenic mice taught us about gonadal function?
Autor:Rulli, S.B.; Huntaniemi, I.
Filiación:Institute of Biology and Experimental Medicine-CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine, Du Cane Road, London W12 0NN, United Kingdom
Palabras clave:follitropin; gonadotropin; gonadotropin receptor; luteinizing hormone; tumor promoter; climacterium; endocrine function; fertility; gametogenesis; gene mutation; gene overexpression; genetic analysis; genetic model; genital system disease; gonad dysfunction; gonad function; gonadotropin release; human; hypogonadotropic hypogonadism; hypophysis tumor; infertility; menopause; mouse; nonhuman; ovary function; ovary polycystic disease; pathogenesis; phenotype; pregnancy; priority journal; review; testis function; transgenic mouse; Animals; Chorionic Gonadotropin; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Luteinizing Hormone; Male; Mice; Mice, Transgenic; Models, Animal; Ovary; Reproduction; Testis; Mus musculus
Año:2005
Volumen:130
Número:3
Página de inicio:283
Página de fin:291
DOI: http://dx.doi.org/10.1530/rep.1.00661
Título revista:Reproduction
Título revista abreviado:Reproduction
ISSN:14701626
CODEN:RCUKB
CAS:follitropin, 9002-68-0; gonadotropin, 63231-54-9; luteinizing hormone, 39341-83-8, 9002-67-9; Chorionic Gonadotropin; Follicle Stimulating Hormone, 9002-68-0; Gonadotropins, Pituitary; Luteinizing Hormone, 9002-67-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14701626_v130_n3_p283_Rulli

Referencias:

  • Ahtiainen, P., Rulli, S., Pelliniemi, L.J., Toppari, J., Poutanen, M., Huhtaniemi, I., Fetal but not adult Leydig cells are susceptible to adenoma formation in response to persistently high hCG level; a study on hCG overexpressing transgenic mice (2005) Oncogene, , In Press
  • Allan, C.M., Garcia, A., Spaliviero, J., Zhang, F.P., Jimenez, M., Huhtaniemi, I., Handelsman, D.J., Complete Sertoli cell proliferation induced by follicle-stimulating hormone (FSH) independently of luteinizing hormone activity: Evidence from genetic models of isolated FSH action (2004) Endocrinology, 145, pp. 1587-1593
  • Amsterdam, A., Selvaraj, N., Control of differentiation, transformation, and apoptosis in granulosa cells by oncogenes, oncoviruses, and tumour suppressor genes (1997) Endocrine Reviews, 18, pp. 435-461
  • Ascoli, M., Fanelli, F., Segaloff, D.L., The lutropin/choriogonadotropin receptor, a 2002 perspective (2002) Endocrine Reviews, 23, pp. 141-174
  • Britt, K.L., Drummond, A.E., Dyson, M., Wreford, N.G., Jones, M.E., Simpson, E.R., Findlay, J.K., The ovarian phenotype of the aromatase knockout (ArKO) mouse (2001) Journal of Steroid Biochemistry and Molecular Biology, 79, pp. 181-185
  • Burger, L.L., Haisenleder, D.J., Dalkin, A.C., Marshall, J.C., Regulation of gonadotropin subunit gene transcription (2004) Journal of Molecular Endocrinology, 33, pp. 559-584
  • Burns, K.H., Matzuk, M.M., Minireview: Genetic models for the study of gonadotropin actions (2002) Endocrinology, 143, pp. 2823-2835
  • Clevenger, C.V., Furth, P.A., Hankinson, S.E., Schuler, L.A., The role of prolactin in mammary carcinoma (2003) Endocrine Reviews, 24, pp. 1-27
  • Cole, L.A., Butler, S., Detection of hCG in trophoblastic disease. The USA hCG reference service experience (2002) Journal of Reproductive Medicine, 47, pp. 433-444
  • Conti, M., Harwood, J.P., Hsueh, A.J., Dufau, M.L., Catt, K.J., Gonadotropin-induced loss of hormone receptors and desensitization of adenylate cyclase in the ovary (1976) Journal of Biological Chemistry, 251, pp. 7729-7731
  • Couse, J.F., Bunch, D.O., Lindzey, J., Schomberg, D.W., Korach, K.S., Prevention of the polycystic ovarian phenotype and characterization of ovulatory capacity in the estrogen receptor-alpha knockout mouse (1999) Endocrinology, 140, pp. 5855-5865
  • Couse, J.F., Hewitt, S.C., Bunch, D.O., Sar, M., Walker, V.R., Davis, B.J., Korach, K.S., Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta (1999) Science, 286, pp. 2328-2331
  • Delvigne, A., Rozenberg, S., Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): A review (2002) Human Reproduction Update, 8, pp. 559-577
  • Dufau, M.L., Cigorraga, S., Baukal, A.J., Sorrell, S., Bator, J.M., Neubauer, J.F., Catt, K.J., Androgen biosynthesis in Leydig cells after testicular desensitization by luteinizing hormone-releasing hormone and human chorionic gonadotropin (1979) Endocrinology, 105, pp. 1314-1321
  • Eddy, E.M., Washburn, T.F., Bunch, D.O., Goulding, E.H., Gladen, B.C., Lubahn, D.B., Korach, K.S., Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility (1996) Endocrinology, 137, pp. 4796-4805
  • Fevold, S.L., Hisaw, F.L., Leonard, S.L., The gonad-stimulating and the luteinizing hormones of the anterior lobe of the hypophysis (1931) American Journal of Physiology, 97, pp. 291-301
  • Filicori, M., Fazleabas, A.T., Huhtaniemi, I., Licht, P., Rao, Ch.V., Tesarik, J., Zygmunt, M., Novel concepts of human chorionic gonadotropin; reproductive system interactions and potentials in the management of infertility (2005) Fertility and Sterility, , In Press
  • Flaws, J.A., Abbud, R., Mann, R.J., Nilson, J.H., Hirshfield, A.N., Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary (1997) Biology of Reproduction, 57, pp. 1233-1237
  • Franks, S., McCarthy, M., Genetics of ovarian disorders: Polycystic ovary syndrome (2004) Reviews of Endocrine and Metabolic Disorders, 5, pp. 69-76
  • Freeman, M.E., Kanyicska, B., Lerant, A., Nagy, G., Prolactin: Structure, function, and regulation of secretion (2000) Physiology Reviews, 80, pp. 1523-1631
  • Gaytan, F., Pinilla, L., Romero, J.L., Aguilar, E., Differential effects of the administration of human chorionic gonadotropin to postnatal rats (1994) Journal of Endocrinology, 142, pp. 527-534
  • Gnagy, S., Ming, E.E., Devesa, S.S., Hartge, P., Whittemore, A.S., Declining ovarian cancer rates in US women in relation to parity and oral contraceptive use (2000) Epidemiology, 11, pp. 102-105
  • Gromoll, J., Simoni, M., Nieschlag, E., An activating mutation of the follicle-stimulating hormone receptor autonomously sustains spermatogenesis in a hypophysectomized man (1996) Journal of Clinical Endocrinology and Metabolism, 81, pp. 1367-1370
  • Huhtaniemi, I.T., Themmen, A.P.N., Mutations in human gonadotropin and gonadotropin receptor genes (2005) Endocrine, , In Press
  • Huhtaniemi, I., Zhang, F.P., Kero, J., Hamalainen, T., Poutanen, M., Transgenic and knockout mouse models for the study of luteinizing hormone and luteinizing hormone receptor function (2002) Molecular and Cellular Endocrinology, 87, pp. 49-56
  • Huhtaniemi, I., Rulli, S., Ahtiainen, P., Poutanen, M., Multiple sites of tumorigenesis in transgenic mice overproducing hCG (2005) Molecular and Cellular Endocrinology, 234, pp. 117-126
  • Huirne, J.A., Lambalk, C.B., Gonadotropin-releasing hormone-receptor antagonists (2001) Lancet, 358, pp. 1793-1803
  • Jameson, J.L., Hollenberg, A.N., Regulation of chorionic gonadotropin gene expression (1993) Endocrine Reviews, 14, pp. 203-221
  • Kananen, K., Rilianawati Paukku, T., Markkula, M., Rainio, E.M., Huhtanemi, I.T., Suppression of gonadotropins inhibits gonadal tumorigenesis in mice transgenic for the mouse inhibin α-subunit promoter/simian virus 40 T antigen fusion gene (1997) Endocrinology, 138, pp. 3521-3531
  • Keri, R.A., Lozada, K.L., Abdul-Karim, F.W., Nadeau, J.N., Nilson, J.H., Luteinizing hormone induction of ovarian tumors: Oligogenic differences between mouse strains dictates tumor disposition (2000) PNAS, 97, pp. 383-387
  • Kero, J., Poutanen, M., Zhang, F.P., Rahman, N., McNicol, A.M., Nilson, J.H., Keri, R.A., Huhtaniemi, I.T., Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex (2000) Journal of Clinical Investigation, 105, pp. 633-641
  • Konishi, I., Kuroda, H., Mandai, M., Review: Gonadotropins and development of ovarian cancer (1999) Oncology, 57, pp. 45-48
  • Kumar, T.R., Wang, Y., Matzuk, M.M., Gonadotropins are essential modifier factors for gonadal tumor development in inhibin-deficient mice (1996) Endocrinology, 137, pp. 4210-4216
  • Kumar, T.R., Palapattu, G., Wang, P., Woodruff, T.K., Boime, I., Byrne, M.C., Matzuk, M.M., Transgenic models to study gonadotropin function: The role of follicle-stimulating hormone in gonadal growth and tumorigenesis (1999) Molecular Endocrinology, 13, pp. 851-886
  • Kumar, T.R., What have we learned about gonadotropin function from gonadotropin subunit and receptor mice? (2005) Reproduction, 130, pp. 293-302
  • La Vecchia, C., Epidemiology of ovarian cancer: A summary review (2001) European Journal of Cancer Prevention, 10, pp. 125-129
  • Liu, G., Duranteau, L., Carel, J.C., Monroe, J., Doyle, D.A., Shenker, A., Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor (1999) New England Journal of Medicine, 341, pp. 1731-1736
  • Mann, R.J., Keri, R.A., Nilson, J.H., Transgenic mice with chronically elevated luteinizing hormone are infertile due to anovulation, defects in uterine receptivity, and midgestation pregnancy failure (1999) Endocrinology, 140, pp. 2592-2601
  • Mann, R.J., Keri, R.A., Nilson, J.H., Consequences of elevated luteinizing hormone on diverse physiological systems: Use of the LHbetaCTP transgenic mouse as a model of ovarian hyperstimulation-induced pathophysiology (2003) Recent Progress in Hormone Research, 58, pp. 343-375
  • Marshall, J.C., Eagleson, C.A., McCartney, C.R., Hypothalamic dysfunction (2001) Molecular and Cellular Endocrinology, 183, pp. 29-32
  • Matzuk, M.M., Finegold, M.J., Su, J.G., Hsueh, A.J., Bradley, A., Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice (1992) Nature, 360, pp. 313-319
  • Matzuk, M.M., DeMayo, F.J., Hadsell, L.A., Kumar, T.R., Overexpression of human chorionic gonadotropin causes multiple reproductive defects in transgenic mice (2003) Biology of Reproduction, 69, pp. 338-346
  • Meehan, T.P., Harmon, B.G., Overcast, M.E., Yu, K.K., Camper, S.A., Puett, D., Narayan, P., Gonadal defects and hormonal alterations in transgenic mice expressing a single chain human chorionic gonadotropin-lutropin receptor complex (2005) Journal of Molecular Endocrinology, 34, pp. 489-503
  • Mikola, M., Kero, J., Nilson, J.H., Keri, R.A., Poutanen, M., Huhtaniemi, I., High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-alpha-subunit promoter/Simian virus 40 T-antigen fusion gene (2003) Oncogene, 22, pp. 3269-3278
  • Mutter, G.L., Role of imprinting in abnormal human development (1997) Mutation Research, 396, pp. 141-147
  • Narayan, P., Gray, J., Puett, D., Yoked complexes of human choriogonadotropin and the lutropin receptor: Evidence that monomeric individual subunits are inactive (2002) Molecular Endocrinology, 16, pp. 2733-2745
  • Owens, G.E., Keri, R.A., Nilson, J.H., Ovulatory surges of hCG prevent hormone-induced granulosa cell tumor formation leading to the identification of tumor-associated changes in the transcriptome (2002) Molecular Endocrinology, 16, pp. 1230-1242
  • Quigley, C.A., Editorial: The postnatal gonadotropin and sex steroid surge - Insights from the androgen insensitivity syndrome (2002) Journal of Clinical Endocrinology and Metabolism, 87, pp. 24-28
  • Pakarainen, T., Zhang, F.-P., Poutanen, M., Huhtaniemi, I., Fertility in LH receptor knockout mice after wild-type ovary transplantation demonstrates redundancy of extragonadal LH action (2005) Journal of Clinical Investigation, , In Press
  • Richter-Unruh, A., Wessels, H.T., Menken, U., Bergmann, M., Schmittmann-Ohters, K., Schaper, J., Tappeser, S., Hauffa, B.P., Male LH-independent sexual precocity in a 3.5-year-old boy caused by a somatic activating mutation of the LH receptor in a Leydig cell tumor (2002) Journal of Clinical Endocrinology and Metabolism, 87, pp. 1052-1056
  • Riman, T., Nilsson, S., Persson, I.R., Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies (2004) Acta Obstetrica Et Gynecologica Scandinavica, 83, pp. 783-795
  • Risbridger, G.P., Robertson, D.M., de Kretser, D.M., The effects of chronic human chorionic gonadotropin treatment on Leydig cell function (1982) Endocrinology, 110, pp. 138-145
  • Risch, H.A., Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone (1998) Journal of the National Cancer Institute, 90, pp. 1774-1786
  • Risma, K.A., Clay, C.M., Nett, T.M., Wagner, T., Yun, J., Nilson, J.H., Targeted overexpression of luteinizing hormone in transgenic mice leads to infertility, polycystic ovaries, and ovarian tumors (1995) PNAS, 92, pp. 1322-1326
  • Risma, K.A., Hirshfield, A.N., Nilson, J.H., Elevated luteinizing hormone in prepubertal transgenic mice causes hyperandrogenemia, precocious puberty, and substantial ovarian pathology (1997) Endocrinology, 138, pp. 3540-3547
  • Roberts, J.E., Spandorfer, S., Fasouliotis, S.J., Lin, K., Rosenwaks, Z., Spontaneous ovarian hyperstimulation caused by a follicle-stimulating hormone-secreting pituitary adenoma (2005) Fertility and Sterility, 83, pp. 208-210
  • Rulli, S.B., Kuorelahti, A.I., Karaer, O., Pelliniemi, L., Poutanen, M., Huhtaniemi, I.T., Reproductive disturbances, pituitary lactotrope adenomas, and mammary gland tumors in transgenic female mice producing high levels of human chorionic gonadotropin (2002) Endocrinology, 143, pp. 4084-4095
  • Rulli, S.B., Ahtiainen, P., Makela, S., Toppari, J., Poutanen, M., Huhtaniemi, I., Elevated steroidogenesis, defective reproductive organs, and infertility in transgenic male mice overexpressing human chorionic gonadotropin (2003) Endocrinology, 144, pp. 4980-4990
  • Salbenblatt, J.A., Bender, B.G., Puck, M.H., Robinson, A., Faiman, C., Winter, J.S., Pituitary-gonadal function in Klinefelter syndrome before and during puberty (1985) Pediatric Research, 19, pp. 82-86
  • Schomberg, D.W., Couse, J.F., Mukherjee, A., Lubahn, D.B., Sar, M., Mayo, K.E., Korach, K.S., Targeted disruption of the estrogen receptor-alpha gene in female mice: Characterization of ovarian responses and phenotype in the adult (1999) Endocrinology, 140, pp. 2733-2744
  • Scott, I.S., Charlton, H.M., Cox, B.S., Grocock, C.A., Sheffield, J.W., O'Shaughnessy, P.J., Effect of LH injections on testicular steroidogenesis, cholesterol sidechain cleavage P450 mRNA content and Leydig cell morphology in hypogonadal mice (1990) Journal of Endocrinology, 125, pp. 131-138
  • Simoni, M., Gromoll, J., Nieschlag, E., The follicle-stimulating hormone receptor: Biochemistry, molecular biology, physiology, and pathophysiology (1997) Endocrine Reviews, 18, pp. 739-773
  • Smith, P.E., Engle, E.T., Experimental evidence of the role of anterior pituitary in development and regulation of gonads (1927) American Journal of Anatomy, 40, pp. 159-161
  • Smits, G., Olatunbosun, O., Delbaere, A., Pierson, R., Vassart, G., Costagliola, S., Ovarian hyperstimulation syndrome due to a mutation in the follicle-stimulating hormone receptor (2003) New England Journal of Medicine, 349, pp. 760-766
  • Stenman, U.H., Alfthan, H., Hotakainen, K., Human chorionic gonadotropin in cancer (2004) Clinical Biochemistry, 37, pp. 549-561
  • Strauss, B.L., Pittman, R., Pixley, M.R., Nilson, J.H., Boime, I., Expression of the beta subunit of chorionic gonadotropin in transgenic mice (1994) Journal of Biological Chemistry, 269, pp. 4968-4973
  • Themmen, A.P.N., Huhtaniemi, I.T., Mutations of gonadotropins and gonadotropin receptors: Elucidating the physiology and pathophysiology of pituitary-gonadal function (2000) Endocrine Reviews, 21, pp. 551-583
  • Themmen, A.P.N., An update of the pathophysiology of human gonadotrophin subunit and receptor mutations and polymorphisms (2005) Reproduction, 130, pp. 263-274
  • Ulbright, T.M., Gonadal teratomas: A review and speculation (2004) Advances in Anatomy and Pathology, 11, pp. 10-23
  • Vasseur, C., Rodien, P., Beau, I., Desroches, A., Gerard, C., de Poncheville, L., Chaplot, S., Misrahi, M., A chorionic gonadotropin-sensitive mutation in the follicle-stimulating hormone receptor as a cause of familial gestational spontaneous ovarian hyperstimulation syndrome (2003) New England Journal of Medicine, 349, pp. 753-759

Citas:

---------- APA ----------
Rulli, S.B. & Huntaniemi, I. (2005) . What have gonadotrophin overexpressing transgenic mice taught us about gonadal function?. Reproduction, 130(3), 283-291.
http://dx.doi.org/10.1530/rep.1.00661
---------- CHICAGO ----------
Rulli, S.B., Huntaniemi, I. "What have gonadotrophin overexpressing transgenic mice taught us about gonadal function?" . Reproduction 130, no. 3 (2005) : 283-291.
http://dx.doi.org/10.1530/rep.1.00661
---------- MLA ----------
Rulli, S.B., Huntaniemi, I. "What have gonadotrophin overexpressing transgenic mice taught us about gonadal function?" . Reproduction, vol. 130, no. 3, 2005, pp. 283-291.
http://dx.doi.org/10.1530/rep.1.00661
---------- VANCOUVER ----------
Rulli, S.B., Huntaniemi, I. What have gonadotrophin overexpressing transgenic mice taught us about gonadal function?. Reproduction. 2005;130(3):283-291.
http://dx.doi.org/10.1530/rep.1.00661