The Experts below are selected from a list of 180 Experts worldwide ranked by ideXlab platform
K L Parker - One of the best experts on this subject based on the ideXlab platform.
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0888-8809/02/$15.00/0 Molecular Endocrinology 16(10):2360–2370 Printed in U.S.A. Copyright © 2002 by The Endocrine Society doi: 10.1210/me.2002-0003 Development of a Transgenic Green Fluorescent Protein Lineage Marker for Steroidogenic Factor 1
2013Co-Authors: Nancy R Stallings, Marit Bakke, Gregor Majdic, Neil A Hanley, Liping Zhao, K L ParkerAbstract:Knockout mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and Gonadal Agenesis, impaired expression of pituitary gonadotropins, and structural abnormalities of the ventromedial hypothalamic nucleus. To explore further how SF-1 regulates endocrine function, we used bacterial artificial chromosome transgenesis to develop a lineage marker for SF-1-expressing cells. A genomic fragment containing 50 kb of the mouse Nr5a1 gene was used to target enhanced green fluorescent protein (eGFP) in transgenic mice. These sequences directed eGFP to multiple cell lineages that express SF-1, including steroidogenic cells of the adrenal cortex, testes, and ovaries, neurons of the ventromedial hypothalamic nucleus, and reticuloendothelial cells of the spleen. Despite the proven role of SF-1 in gonadotrope function, eGFP was not expressed in the anterior pituitary. These experiments show that 50 kb of the mouse Nr5a1 gene can target transgenic expression to multiple cell lineages that normally express SF-1. The SF-1/eGFP transgenic mice will facilitate approaches such as fluorescence-activated cell sorting of eGFP-positive cells and DNA microarray analyses to expand our understanding of the multiple actions of SF-1 in endocrine development an
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cell specific knockout of steroidogenic factor 1 reveals its essential roles in Gonadal function
Molecular Endocrinology, 2004Co-Authors: Pancharatnam Jeyasuria, Soazik P Jamin, Axel P N Themmen, Richard R Behringer, Yayoi Ikeda, Dirk G. De Rooij, K L ParkerAbstract:Knockout (KO) mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a compound endocrine phenotype that includes adrenal and Gonadal Agenesis, impaired expression of pituitary gonadotropins, and structural abnormalities of the ventromedial hypothalamic nucleus. To inactivate a conditional SF-1 allele in the gonads, we targeted the expression of Cre recombinase with a knock-in allele of the anti-Mullerian hormone type 2 receptor locus. In testes, Cre was expressed in Leydig cells. The testes of adult gonad-specific SF-1 KO mice remained at the level of the bladder and were markedly hypoplastic, due at least partly to impaired spermatogenesis. Histological abnormalities of the testes were seen from early developmental stages and were associated with markedly decreased Leydig cell expression of two essential components of testosterone biosynthesis, Cyp11a and the steroidogenic acute regulatory protein. In females, the anti-Mullerian hormone type 2 receptor-C...
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A microdeletion in the ligand binding domain of human steroidogenic factor 1 causes XY sex reversal without adrenal insufficiency.
The Journal of clinical endocrinology and metabolism, 2004Co-Authors: Rafaela Vieira Correa, K L Parker, Sorahia Domenice, Nathan C. Bingham, Ana Elisa C. Billerbeck, William E. Rainey, Berenice B. MendoncaAbstract:Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor that plays key roles in endocrine development and function. Knockout mice lacking SF-1 have adrenal and Gonadal Agenesis, impaired gonadotropin expression, and structural abnormalities of the ventromedial hypothalamic nucleus. Previous studies have identified three human subjects with mutations in SF-1 causing adrenocortical insufficiency with varying degrees of Gonadal dysfunction. We now describe a novel 8-bp microdeletion of SF-1, isolated from a 46, XY patient who presented with Gonadal Agenesis but normal adrenal function, which causes premature termination upstream of sequences encoding the activation function 2 domain. In cell transfection experiments, the mutated protein possessed no intrinsic transcriptional activity but rather inhibited the function of the wild-type protein in most cell types. To our knowledge, this is the first example of an apparent dominant-negative effect of a SF-1 mutation in humans. These findings, which define a SF-1 mutation that apparently differentially affects its transcriptional activity in vivo in the adrenal cortex and the gonads, may be relevant to the cohort of patients who present with 46, XY sex reversal but normal adrenal function.
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development of a transgenic green fluorescent protein lineage marker for steroidogenic factor 1
Molecular Endocrinology, 2002Co-Authors: Nancy R Stallings, Marit Bakke, Gregor Majdic, Neil A Hanley, K L ParkerAbstract:Knockout mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and Gonadal Agenesis, impaired expression of pituitary gonadotropins, and structural abnormalities of the ventromedial hypothalamic nucleus. To explore further how SF-1 regulates endocrine function, we used bacterial artificial chromosome transgenesis to develop a lineage marker for SF-1-expressing cells. A genomic fragment containing 50 kb of the mouse Nr5a1 gene was used to target enhanced green fluorescent protein (eGFP) in transgenic mice. These sequences directed eGFP to multiple cell lineages that express SF-1, including steroidogenic cells of the adrenal cortex, testes, and ovaries, neurons of the ventromedial hypothalamic nucleus, and reticuloendothelial cells of the spleen. Despite the proven role of SF-1 in gonadotrope function, eGFP was not expressed in the anterior pituitary. These experiments show that 50 kb of the mouse Nr5a1 gene can target transgenic expression to...
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Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity
Endocrinology, 2002Co-Authors: Gregor Majdic, Morag J. Young, Elise P. Gomez-sanchez, Paul Anderson, Lidia S. Szczepaniak, Robert L. Dobbins, J. Denis Mcgarry, K L ParkerAbstract:Knockout (KO) mice lacking steroidogenic factor 1 (SF-1) exhibit a phenotype that includes adrenal and Gonadal Agenesis, impaired gonadotropin expression, and abnormalities of the ventromedial hypothalamic nucleus (VMH). Studies in rodents with lesions of the ventromedial hypothalamus have implicated the VMH in body weight regulation, suggesting that SF-1 KO mice may provide a genetic model of obesity. To prevent death, SF-1 KO mice were rescued with corticosteroid injections, followed by syngeneic adrenal transplants from wild-type (WT) littermates. Corticosterone and ACTH levels in WT and SF-1 KO mice were indistinguishable, documenting restoration of hypothalamic-pituitary-adrenal function. Although weights at earlier ages did not differ significantly from WT littermates, SF-1 KO mice were significantly heavier by 8 wk of age and eventually weighed almost twice as much as WT controls. Obesity in SF-1 KO mice predominantly resulted from decreased activity rather than increased food intake. Leptin was increased markedly, insulin was modestly elevated, and glucose was indistinguishable from WT mice. Although sex steroids in rodents affect weight, ovariectomy did not abolish the weight difference between WT and SF-1 KO mice. These SF-1 KO mice are a genetic model of late-onset obesity that may help elucidate the role of the VMH in weight regulation.
P. N. Dogra - One of the best experts on this subject based on the ideXlab platform.
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Management of an unusual case of atypical Mayer–Rokitansky–Kuster–Hauser syndrome, with unilateral Gonadal Agenesis, solitary ectopic pelvic kidney, and pelviureteric junction obstruction
International Urogynecology Journal, 2007Co-Authors: Anup Kumar, Saurabh Mishra, P. N. DograAbstract:Congenital absence of uterus and vagina, Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome, is mullerian Agenesis and is the second most frequent cause of primary amenorrhea. Only atypical form of MRKH (type B) is associated with renal skeletal and ovarian abnormalities. We report the management of an unusual case of atypical MRKH, unilateral Gonadal Agenesis, and solitary ectopic pelvic kidney with pelviureteric junction obstruction (PUJO). After doing thorough Medline search, to the best of our knowledge, this is the first case reported with this combination.
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Management of an unusual case of atypical Mayer-Rokitansky-Kuster-Hauser syndrome, with unilateral Gonadal Agenesis, solitary ectopic pelvic kidney, and pelviureteric junction obstruction.
International urogynecology journal and pelvic floor dysfunction, 2006Co-Authors: Anup Kumar, Saurabh Mishra, P. N. DograAbstract:Congenital absence of uterus and vagina, Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, is mullerian Agenesis and is the second most frequent cause of primary amenorrhea. Only atypical form of MRKH (type B) is associated with renal skeletal and ovarian abnormalities. We report the management of an unusual case of atypical MRKH, unilateral Gonadal Agenesis, and solitary ectopic pelvic kidney with pelviureteric junction obstruction (PUJO). After doing thorough Medline search, to the best of our knowledge, this is the first case reported with this combination.
Anup Kumar - One of the best experts on this subject based on the ideXlab platform.
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Management of an unusual case of atypical Mayer–Rokitansky–Kuster–Hauser syndrome, with unilateral Gonadal Agenesis, solitary ectopic pelvic kidney, and pelviureteric junction obstruction
International Urogynecology Journal, 2007Co-Authors: Anup Kumar, Saurabh Mishra, P. N. DograAbstract:Congenital absence of uterus and vagina, Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome, is mullerian Agenesis and is the second most frequent cause of primary amenorrhea. Only atypical form of MRKH (type B) is associated with renal skeletal and ovarian abnormalities. We report the management of an unusual case of atypical MRKH, unilateral Gonadal Agenesis, and solitary ectopic pelvic kidney with pelviureteric junction obstruction (PUJO). After doing thorough Medline search, to the best of our knowledge, this is the first case reported with this combination.
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Management of an unusual case of atypical Mayer-Rokitansky-Kuster-Hauser syndrome, with unilateral Gonadal Agenesis, solitary ectopic pelvic kidney, and pelviureteric junction obstruction.
International urogynecology journal and pelvic floor dysfunction, 2006Co-Authors: Anup Kumar, Saurabh Mishra, P. N. DograAbstract:Congenital absence of uterus and vagina, Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, is mullerian Agenesis and is the second most frequent cause of primary amenorrhea. Only atypical form of MRKH (type B) is associated with renal skeletal and ovarian abnormalities. We report the management of an unusual case of atypical MRKH, unilateral Gonadal Agenesis, and solitary ectopic pelvic kidney with pelviureteric junction obstruction (PUJO). After doing thorough Medline search, to the best of our knowledge, this is the first case reported with this combination.
Marit Bakke - One of the best experts on this subject based on the ideXlab platform.
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0888-8809/02/$15.00/0 Molecular Endocrinology 16(10):2360–2370 Printed in U.S.A. Copyright © 2002 by The Endocrine Society doi: 10.1210/me.2002-0003 Development of a Transgenic Green Fluorescent Protein Lineage Marker for Steroidogenic Factor 1
2013Co-Authors: Nancy R Stallings, Marit Bakke, Gregor Majdic, Neil A Hanley, Liping Zhao, K L ParkerAbstract:Knockout mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and Gonadal Agenesis, impaired expression of pituitary gonadotropins, and structural abnormalities of the ventromedial hypothalamic nucleus. To explore further how SF-1 regulates endocrine function, we used bacterial artificial chromosome transgenesis to develop a lineage marker for SF-1-expressing cells. A genomic fragment containing 50 kb of the mouse Nr5a1 gene was used to target enhanced green fluorescent protein (eGFP) in transgenic mice. These sequences directed eGFP to multiple cell lineages that express SF-1, including steroidogenic cells of the adrenal cortex, testes, and ovaries, neurons of the ventromedial hypothalamic nucleus, and reticuloendothelial cells of the spleen. Despite the proven role of SF-1 in gonadotrope function, eGFP was not expressed in the anterior pituitary. These experiments show that 50 kb of the mouse Nr5a1 gene can target transgenic expression to multiple cell lineages that normally express SF-1. The SF-1/eGFP transgenic mice will facilitate approaches such as fluorescence-activated cell sorting of eGFP-positive cells and DNA microarray analyses to expand our understanding of the multiple actions of SF-1 in endocrine development an
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development of a transgenic green fluorescent protein lineage marker for steroidogenic factor 1
Molecular Endocrinology, 2002Co-Authors: Nancy R Stallings, Marit Bakke, Gregor Majdic, Neil A Hanley, K L ParkerAbstract:Knockout mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and Gonadal Agenesis, impaired expression of pituitary gonadotropins, and structural abnormalities of the ventromedial hypothalamic nucleus. To explore further how SF-1 regulates endocrine function, we used bacterial artificial chromosome transgenesis to develop a lineage marker for SF-1-expressing cells. A genomic fragment containing 50 kb of the mouse Nr5a1 gene was used to target enhanced green fluorescent protein (eGFP) in transgenic mice. These sequences directed eGFP to multiple cell lineages that express SF-1, including steroidogenic cells of the adrenal cortex, testes, and ovaries, neurons of the ventromedial hypothalamic nucleus, and reticuloendothelial cells of the spleen. Despite the proven role of SF-1 in gonadotrope function, eGFP was not expressed in the anterior pituitary. These experiments show that 50 kb of the mouse Nr5a1 gene can target transgenic expression to...
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development of a transgenic green fluorescent protein lineage marker for steroidogenic factor 1
Endocrine Research, 2002Co-Authors: Nancy R Stallings, Marit Bakke, Gregor Majdic, Neil A Hanley, K L ParkerAbstract:Knockout (KO) mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and Gonadal Agenesis, impaired function of pituitary gonadotropes, and abnormalities of the ventromedial hypothalamic nucleus (VMH). To develop a lineage marker for cells that express SF-1, we used bacterial artificial chromosome (BAC) transgenesis. A BAC fragment containing 50 kb of the mouse Nr5a1 gene was placed upstream of the coding sequence for enhanced green fluorescent protein (eGFP) and used to generate SF-1/eGFP transgenic mice. These sequences directed eGFP expression to multiple cell lineages that express SF-1, including steroidogenic cells of the adrenal cortex, testes, and ovaries, VMH neurons, and reticuloendothelial cells of the spleen. Despite the essential role of SF-1 in gonadotropes, eGFP was not expressed in the anterior pituitary. These studies show that 50 kb of the mouse Nr5a1 gene can target transgenic expression to multiple cell lineages that normally express SF-1. The SF-1/eGFP transgene provides a valuable tool to expand our understanding of the actions of SF-1 in endocrine development and function.
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DEVELOPMENT OF A TRANSGENIC GREEN FLUORESCENT PROTEIN LINEAGE MARKER FOR STEROIDOGENIC FACTOR 1
Molecular endocrinology (Baltimore Md.), 2002Co-Authors: Nancy R Stallings, Marit Bakke, Gregor Majdic, Neil A Hanley, Liping Zhao, K L ParkerAbstract:Knockout mice lacking steroidogenic factor 1 (SF-1, officially designated Nr5a1) have a complex phenotype that includes adrenal and Gonadal Agenesis, impaired expression of pituitary gonadotropins, and structural abnormalities of the ventromedial hypothalamic nucleus. To explore further how SF-1 regulates endocrine function, we used bacterial artificial chromosome transgenesis to develop a lineage marker for SF-1-expressing cells. A genomic fragment containing 50 kb of the mouse Nr5a1 gene was used to target enhanced green fluorescent protein (eGFP) in transgenic mice. These sequences directed eGFP to multiple cell lineages that express SF-1, including steroidogenic cells of the adrenal cortex, testes, and ovaries, neurons of the ventromedial hypothalamic nucleus, and reticuloendothelial cells of the spleen. Despite the proven role of SF-1 in gonadotrope function, eGFP was not expressed in the anterior pituitary. These experiments show that 50 kb of the mouse Nr5a1 gene can target transgenic expression to multiple cell lineages that normally express SF-1. The SF-1/eGFP transgenic mice will facilitate approaches such as fluorescence-activated cell sorting of eGFP-positive cells and DNA microarray analyses to expand our understanding of the multiple actions of SF-1 in endocrine development and function.
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steroidogenic factor 1 sf1 is essential for pituitary gonadotrope function
Development, 2001Co-Authors: Marit Bakke, Yelena Krimkevich, Albert F Parlow, Lisa J Cushman, Sally A Camper, K L ParkerAbstract:Knockout mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF1) exhibit a complex endocrine phenotype that includes adrenal and Gonadal Agenesis, impaired expression of pituitary gonadotropins, and absence of the ventromedial hypothalamic nucleus (VMH). These multiple defects complicate efforts to delineate primary versus secondary effects of SF1 deficiency in different tissues, such that its direct role in gonadotropes remains uncertain. To define this role, we have expressed Cre recombinase driven by the promoter region of the common alpha subunit of glycoprotein hormones (alpha GSU), thereby inactivating a loxP-modified SF1 locus in the anterior pituitary gland. Although pituitary-specific SF1 knockout mice were fully viable, they were sterile and failed to develop normal secondary sexual characteristics. Their adrenal glands and VMH appeared normal histologically, but their testes and ovaries were severely hypoplastic. alpha GSU-Cre, loxP mice had normal levels of most pituitary hormones, but had markedly decreased expression of LH and FSH. Treatment with exogenous gonadotropins stimulated Gonadal steroidogenesis, inducing germ cell maturation in males and follicular and uterine maturation in females--establishing that the gonads can respond to gonadotropins. The pituitary-specific SF1 knockout mice are a novel genetic model of hypogonadotropic hypogonadism that establishes essential role(s) of SF1 in pituitary gonadotropes.
Saurabh Mishra - One of the best experts on this subject based on the ideXlab platform.
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Management of an unusual case of atypical Mayer–Rokitansky–Kuster–Hauser syndrome, with unilateral Gonadal Agenesis, solitary ectopic pelvic kidney, and pelviureteric junction obstruction
International Urogynecology Journal, 2007Co-Authors: Anup Kumar, Saurabh Mishra, P. N. DograAbstract:Congenital absence of uterus and vagina, Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome, is mullerian Agenesis and is the second most frequent cause of primary amenorrhea. Only atypical form of MRKH (type B) is associated with renal skeletal and ovarian abnormalities. We report the management of an unusual case of atypical MRKH, unilateral Gonadal Agenesis, and solitary ectopic pelvic kidney with pelviureteric junction obstruction (PUJO). After doing thorough Medline search, to the best of our knowledge, this is the first case reported with this combination.
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Management of an unusual case of atypical Mayer-Rokitansky-Kuster-Hauser syndrome, with unilateral Gonadal Agenesis, solitary ectopic pelvic kidney, and pelviureteric junction obstruction.
International urogynecology journal and pelvic floor dysfunction, 2006Co-Authors: Anup Kumar, Saurabh Mishra, P. N. DograAbstract:Congenital absence of uterus and vagina, Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, is mullerian Agenesis and is the second most frequent cause of primary amenorrhea. Only atypical form of MRKH (type B) is associated with renal skeletal and ovarian abnormalities. We report the management of an unusual case of atypical MRKH, unilateral Gonadal Agenesis, and solitary ectopic pelvic kidney with pelviureteric junction obstruction (PUJO). After doing thorough Medline search, to the best of our knowledge, this is the first case reported with this combination.