Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation
Open accessAbstract
Human sexual determination is initiated by a cascade of genes that lead to the development of the fetal gonad. Whereas development of the female external genitalia does not require fetal ovarian hormones, male genital development requires the action of testicular testosterone and its more potent derivative dihydrotestosterone (DHT). The "classic" biosynthetic pathway from cholesterol to testosterone in the testis and the subsequent conversion of testosterone to DHT in genital skin is well established. Recently, an alternative pathway leading to DHT has been described in marsupials, but its potential importance to human development is unclear. AKR1C2 is an enzyme that participates in the alternative but not the classic pathway. Using a candidate gene approach, we identified AKR1C2 mutations with sex-limited recessive inheritance in four 46,XY individuals with disordered sexual development (DSD). Analysis of the inheritance of microsatellite markers excluded other candidate loci. Affected individuals had moderate to severe undervirilization at birth; when recreated by site-directed mutagenesis and expressed in bacteria, the mutant AKR1C2 had diminished but not absent catalytic activities. The 46,XY DSD individuals also carry a mutation causing aberrant splicing in AKR1C4, which encodes an enzyme with similar activity. This suggests a mode of inheritance where the severity of the developmental defect depends on the number of mutations in the two genes. An unrelated 46,XY DSD patient carried AKR1C2 mutations on both alleles, confirming the essential role of AKR1C2 and corroborating the hypothesis that both the classic and alternative pathways of testicular androgen biosynthesis are needed for normal human male sexual differentiation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both the canonical and backdoor pathways are essential for normal fetal masculinization.
“These data demonstrate that both the canonical and backdoor pathways are essential for normal fetal masculinization.”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [15]
Disruption of the backdoor pathway causes disordered sex development (DSD) and failure of normal masculinization.
“studies by Flück and colleagues [15] have shown that disordered sex development (DSD) will arise if the pathway is disrupted. In one individual with mutations in aldo-keto reductase type 1C2 (AKR1C2) and in another family with an added mutation in aldo-keto reductase type 1C4 (AKR1C4), there was failure of normal masculinization.”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [15]
The currently accepted model for masculinization is that circulating DHT, formed via the backdoor pathway in the fetal testis, is important for virilization alongside circulating testosterone.
“Currently, the accepted model for masculinization is that circulating DHT, formed via the backdoor pathway in the fetal testis [15,16], is important for virilization alongside circulating testosterone.”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [15]
An alternative 'backdoor' pathway to DHT formation exists that does not require testosterone as an intermediate.
“More recently, however, it has been reported that an alternative pathway to DHT formation exists that does not require testosterone as an intermediate. This alternative, “backdoor” pathway (Fig 1) was first described in the testes of pouch young marsupials [13], and a similar pathway has since been reported in the prepubertal mouse testis [14] and the fetal human testis [15].”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [15]
Masculinization of the external genitalia in humans depends on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway.
“Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway.”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [15]
The recent demonstration that the alternative, backdoor pathway to DHT synthesis is also required for normal human fetal male development has shown that the process involves a complex interaction between different steroidogenic pathways.
“However, the recent demonstration that the alternative, backdoor pathway to DHT synthesis is also required for normal human fetal male development [15,16] has shown that the process involves a complex interaction between different steroidogenic pathways.”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [15]
Two 46,XY individuals who are known heterozygotes for a mutation in AKR1C2 show divergent phenotypes, with one showing a normal male phenotype and the other DSD.
“two 46,XY individuals who are known heterozygotes for a mutation in AKR1C2 show divergent phenotypes, with one showing a normal male phenotype and the other DSD [15]”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [15]
The normal process of masculinization in the human depends on two separate pathways of androgen synthesis, the canonical and backdoor pathways.
“the normal process of masculinization in the human depends on two separate pathways of androgen synthesis, the canonical and backdoor pathways [15]”
From Alternative (backdoor) androgen production and masculinization in the human fetus (2019) · cites this paper as [15]
Several inherited mutations in AKR1C2 and AKR1C4 have been identified in two Swiss families with disordered sexual dysgenesis.
“Recently several inherited mutations in the AKR1C2 and AKR1C4 genes have been identified in two Swiss families which were associated with disordered sexual dysgenesis (DSD).”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [103]
Mutants Ile79Val, His90Gln, Asn300Thr, and His222Gln prepared in recombinant forms or over-expressed in COS-1 cells showed reduced enzymatic activities.
“The mutants Ile79Val, His90Gln, Asn300Thr and His222Gln have been prepared in recombinant forms or over-expressed in COS-1 cells and showed reduced enzymatic activities [103].”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [103]
The authors observed AKR1C2 and AKR1C4 expression in fetal testes and concluded these enzymes are needed for fetal 5α-DHT synthesis via the backdoor pathway and normal genital development.
“The authors observed AKR1C2 and AKR1C4 expression in fetal testes thus they concluded that these enzymes are needed for fetal 5α-DHT synthesis via the backdoor pathway and normal development of the genitalia [103].”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [103]
These individuals also carried an AKR1C4 mutation causing aberrant splicing (Val29_Lys84del).
“In addition to these AKR1C2 mutations these individuals also carried a mutation causing aberrant splicing of the AKR1C4 gene (Val29_Lys84del).”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [103]
In the first DSD family, missense AKR1C2 mutations Ile79Val, His906Glu, and Asn300Thr were identified in affected individuals.
“In the first family identified with DSD, missense AKR1C2 muations: Ile79Val, His906Glu, and Asn300Thr were identified in the affected individuals.”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [103]
SNPs in AKR1C1, AKR1C2, and AKR1C4 have been studied at the protein level, and Phe46Tyr has been associated with disease.
“So far SNPs in AKR1C1, AKR1C2 and AKR1C4 have been studied at the protein level and Phe46Tyr has been associated with disease [95–97, 99, 103, 104].”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [103]
In the second family, recombination between AKR1C1 and AKR1C3 was detected and a missense AKR1C2 mutation His222Gln was identified.
“In the second family recombination between AKR1C1 and AKR1C3 was detected and a missense AKR1C2 mutation His222Gln was identified.”
From Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism (2014) · cites this paper as [103]
Cites
The Amber biomolecular simulation programs
Case, D. A., Cheatham, T. E., Darden, T., Gohlke, H., Luo, R., Merz, K. M., Onufriev, A., Simmerling, C., Wang, B., & Woods, R. J. (2005) · Journal of Computational Chemistry · doi:10.1002/jcc.20290 · Cited by 9,535 · see citing works
WHAT IF: A molecular modeling and drug design program
Vriend, G. (1990) · Journal of Molecular Graphics · doi:10.1016/0263-7855(90)80070-v · Cited by 3,476 · see citing works
Parametric and nonparametric linkage analysis: a unified multipoint approach.
Kruglyak, L., Daly, M. J., Daly, M. J., & Lander, E. S. (1996) · PubMed Central · Cited by 2,883 · see citing works
Human Splicing Finder: an online bioinformatics tool to predict splicing signals
Desmet, F.-O., Hamroun, D., Lalande, M., Collod‐Béroud, G., Claustres, M., & Béroud, C. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp215 · Cited by 2,500 · see citing works
The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders
Miller, W. L., & Auchus, R. J. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0013 · Cited by 2,458 · see citing works
Self-citationSpeiser, P. W., Azziz, R., Baskin, L. S., Ghizzoni, L., Hensle, T. W., Merke, D. P., Meyer-Bahlburg, H. F. L., Miller, W. L., Montori, V. M., Oberfield, S. E., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2631 · Cited by 1,484 · see citing works
Self-citationKrieger, E., Joo, K., Lee, J., Lee, J., Raman, S., Thompson, J., Tyka, M., Baker, D. A., & Karplus, K. J. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22570 · Cited by 1,396 · see citing works
Steroid 5α-reductase: two genes/two enzymes
Russell, D. W., & Wilson, J. D. (1994) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.63.070194.000325 · Cited by 1,105 · see citing works
Making optimal use of empirical energy functions: Force‐field parameterization in crystal space
Krieger, E., Darden, T., Nabuurs, S. B., Finkelstein, A. V., & Vriend, G. (2004) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.20251 · Cited by 855 · see citing works
PENNING, T. M., BURCZYNSKI, M. E., JEZ, J. M., HUNG, C.-F., LIN, H.-K., MA, H., MOORE, M., PALACKAL, N., & RATNAM, K. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3510067 · Cited by 649 · see citing works
PENNING, T. M., BURCZYNSKI, M. E., JEZ, J. M., HUNG, C.-F., LIN, H.-K., MA, H., MOORE, M., PALACKAL, N., & RATNAM, K. (2000) · Biochemical Journal · doi:10.1042/bj3510067 · Cited by 649 · see citing works
Steroid 5α-reductase 2 deficiency
Mendonca, B. B., Batista, R. L., Domenice, S., Costa, E. M. F., Arnhold, I. J. P., Russell, D. W., & Wilson, J. D. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.05.020 · Cited by 546 · see citing works
Cytochrome b 5 Augments the 17,20-Lyase Activity of Human P450c17 without Direct Electron Transfer
Auchus, R. J., Lee, T. C., & Miller, W. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.6.3158 · Cited by 541 · see citing works
Self-citationMutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome
Flück, C. E., Tajima, T., Pandey, A. V., Arlt, W., Okuhara, K., Verge, C. F., Jabs, E. W., Mendonça, B. B., Fujieda, K., & Miller, W. L. (2004) · Nature Genetics · doi:10.1038/ng1300 · Cited by 509 · see citing works
Self-citationFast empirical pKa prediction by Ewald summation
Krieger, E., Nielsen, J. E., Spronk, C. A. E. M., & Vriend, G. (2006) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2006.02.009 · Cited by 475 · see citing works
Zhang, L. H., Rodriguez, H., Ohno, S., & Miller, W. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.23.10619 · Cited by 455 · see citing works
Self-citationChung, B. C., Picado-Leonard, J., Haniu, M., Bienkowski, M., Hall, P. F., Shively, J. E., & Miller, W. L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.2.407 · Cited by 444 · see citing works
Self-citationGrino, P. B., Griffin, J. E., & Wilson, J. D. (1990) · Endocrinology · doi:10.1210/endo-126-2-1165 · Cited by 434 · see citing works
PICADO-LEONARD, J., & MILLER, W. L. (1987) · DNA · doi:10.1089/dna.1987.6.439 · Cited by 415 · see citing works
Self-citationThe backdoor pathway to dihydrotestosterone
Auchus, R. J. (2004) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2004.09.004 · Cited by 347 · see citing works
Arlt, W., Walker, E. A., Draper, N., Ivison, H. E., Ride, J. P., Hammer, F., Chalder, S. M., Borucka-Mankiewicz, M., Hauffa, B. P., Malunowicz, E. M., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16503-3 · Cited by 345 · see citing works
The genetic and functional basis of isolated 17,20 lyase deficiency
Geller, D. H., Auchus, R. J., Mendonça, B. B., & Miller, W. L. (1997) · Nature Genetics · doi:10.1038/ng1097-201 · Cited by 318 · see citing works
Self-citationMultiple Hits during Early Embryonic Development: Digenic Diseases and Holoprosencephaly
Ming, J. E., & Muenke, M. (2002) · The American Journal of Human Genetics · doi:10.1086/344412 · Cited by 310 · see citing works
Nakajin, S., & Hall, P. F. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69538-4 · Cited by 299 · see citing works
Ovaries and Female Phenotype in a Girl with 46,XY Karyotype and Mutations in the CBX2 Gene
Biason‐Lauber, A., Konrad, D., Meyer‐Böni, M., de Beaufort, C. E., & Schoenle, E. J. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.03.016 · Cited by 296 · see citing works
Self-citationGlock, G. E., & McLean, P. (1955) · Biochemical Journal · doi:10.1042/bj0610388 · Cited by 290 · see citing works
Draper, N., Walker, E. A., Bujalska, I. J., Tomlinson, J. W., Chalder, S. M., Arlt, W., Lavery, G. G., Bedendo, O., Ray, D. W., Laing, I., et al. (2003) · Nature Genetics · doi:10.1038/ng1214 · Cited by 285 · see citing works
Steckelbroeck, S., Jin, Y., Gopishetty, S., Oyesanmi, B., & Penning, T. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313308200 · Cited by 270 · see citing works
Taking geometry to its edge: Fast unbound rigid (and hinge‐bent) docking
Schneidman‐Duhovny, D., Inbar, Y., Polak, V., Shatsky, M., Halperin, I., Benyamini, H., Barzilai, A., Dror, O., Haspel, N., Nussinov, R., et al. (2003) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10397 · Cited by 256 · see citing works
Biswas, M. G., & Russell, D. W. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.25.15959 · Cited by 224 · see citing works
Vockley, J. E., Rinaldo, P., Bennett, M. J., Matern, D., & Vladutiu, G. D. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3066 · Cited by 207 · see citing works
46,XY disorders of sex development (DSD)
Mendonca, B. B., Domenice, S., Arnhold, I. J. P., & Costa, E. M. F. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03392.x · Cited by 207 · see citing works
Huang, N., Agrawal, V., Giacomini, K. M., & Miller, W. L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711621105 · Cited by 198 · see citing works
Self-citationNAD Kinase Levels Control the NADPH Concentration in Human Cells
Pollak, N., Niere, M., & Ziegler, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704442200 · Cited by 197 · see citing works
Lin, H.-K., Jez, J. M., Schlegel, B. P., Peehl, D. M., Pachter, J. A., & Penning, T. M. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.13.0026 · Cited by 194 · see citing works
Barbaccia, M. L., Roscetti, G., Trabucchi, M., Purdy, R. H., Mostallino, M. C., Concas, A., & Biggio, G. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701046 · Cited by 185 · see citing works
Wilson, J. D., Auchus, R. J., Leihy, M. W., Guryev, O. L., Estabrook, R. W., Osborn, S. M., Shaw, G., & Renfree, M. B. (2003) · Endocrinology · doi:10.1210/en.2002-220721 · Cited by 172 · see citing works
The role of androgens in male gender role behavior
Wilson, J. D. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.5.0377 · Cited by 172 · see citing works
The Source of Plasma Dihydrotestosterone in Man
Ito, T., & Horton, R. (1971) · Journal of Clinical Investigation · doi:10.1172/jci106650 · Cited by 166 · see citing works
A cluster of male pseudohermaphrodites with 5α‐reductase deficiency in Papua New Guinea
Imperato‐McGinley, J., Miller, M., Wilson, J. D., Peterson, R. E., Shackleton, C. H. L., & Gajdusek, D. C. (1991) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1991.tb03769.x · Cited by 161 · see citing works
Steroid 17,20 desmolase deficiency: a new cause of male pseudohermaphroditism
ZACHMANN, M., VÖLLMIN, J. A., HAMILTON, W., & PRADER, A. (1972) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1972.tb00407.x · Cited by 160 · see citing works
Fukami, M., Horikawa, R., Nagai, T., Tanaka, T., Naiki, Y., Sato, N., Okuyama, T., Nakai, H., Soneda, S., Tachibana, K., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0810 · Cited by 155 · see citing works
Homma, K., Hasegawa, T., Nagai, T., Adachi, M., Horikawa, R., Fujiwara, I., Tajima, T., Takeda, R., Fukami, M., & Ogata, T. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2460 · Cited by 153 · see citing works
Structure–function of human 3α-hydroxysteroid dehydrogenases: genes and proteins
Penning, T. M., Jin, Y., Steckelbroeck, S., Rižner, T. L., & Lewis, M. (2004) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2003.11.006 · Cited by 142 · see citing works
The simultaneous radioimmunoassay of seven steroids in human spermatic and peripheral venous blood
HAMMOND, G. L., RUOKONEN, A., KONTTURI, M., KOSKELA, E., & VIHKO, R. (1977) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-45-1-16 · Cited by 138 · see citing works
Hoog, S. S., Pawlowski, J. E., Alzari, P. M., Penning, T. M., & Lewis, M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.7.2517 · Cited by 137 · see citing works
Modulation of human CYP19A1 activity by mutant NADPH P450 oxidoreductase
Pandey, A. V., Kempná, P., Hofer, G., Mullis, P. E., & Flück, C. E. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0245 · Cited by 132 · see citing works
Self-citationRižner, T. L., Lin, H. K., Peehl, D. M., Steckelbroeck, S., Bauman, D. R., & Penning, T. M. (2003) · Endocrinology · doi:10.1210/en.2002-0032 · Cited by 132 · see citing works
Fukami, M., Nishimura, G., Homma, K., Nagai, T., Hanaki, K., Uematsu, A., Ishii, T., Numakura, C., Sawada, H., Nakacho, M., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2816 · Cited by 117 · see citing works
Bennett, M. J., Albert, R. H., Jez, J. M., Ma, H., Penning, T. M., & Lewis, M. (1997) · Structure · doi:10.1016/s0969-2126(97)00234-7 · Cited by 117 · see citing works
Quigley, C. A., Friedman, K. J., Johnson, A., Lafrenière, R. G., Silverman, L. M., Lubahn, D. B., Brown, T. R., Wilson, E. M., Willard, H., & French, F. S. (1992) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jcem.74.4.1347772 · Cited by 113 · see citing works
Isolated 17,20-lyase deficiency due to the cytochrome b5 mutation W27X
Kok, R. C., Timmerman, M. A., Wolffenbuttel, K. P., Drop, S. L. S., & de Jong, F. H. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1745 · Cited by 111 · see citing works
Shackleton, C., Marcos, J., Arlt, W., & Hauffa, B. P. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30171 · Cited by 104 · see citing works
Jin, Y., Stayrook, S. E., Albert, R. H., Palackal, N. T., Penning, T. M., & Lewis, M. (2001) · Biochemistry · doi:10.1021/bi010919a · Cited by 99 · see citing works
Hershkovitz, E., Parvari, R., Wudy, S. A., Hartmann, M. F., Gomes, L. G., Loewental, N., & Miller, W. L. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0051 · Cited by 95 · see citing works
Self-citationIsolation and characterization of cloned cDNAs encoding human liver chlordecone reductase
Winters, C., Molowa, D. T., & Guzelian, P. S. (1990) · Biochemistry · doi:10.1021/bi00456a034 · Cited by 94 · see citing works
Structure of 3α-Hydroxysteroid/Dihydrodiol Dehydrogenase Complexed with NADP<sup>+</sup>
Bennett, M. J., Schlegel, B. P., Jez, J. M., Penning, T. M., & Lewis, M. (1996) · Biochemistry · doi:10.1021/bi9604688 · Cited by 92 · see citing works
Dufort, I., Soucy, P., Labrie, F., & Luu-The, V. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1684 · Cited by 84 · see citing works
Mahendroo, M., Wilson, J. D., Richardson, J. A., & Auchus, R. J. (2004) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2004.04.009 · Cited by 75 · see citing works
Human Types 1 and 3 3α-Hydroxysteroid Dehydrogenases: Differential Lability and Tissue Distribution1
Dufort, I., Labrie, F., & Luu-The, V. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.2.7216 · Cited by 73 · see citing works
Královičová, J., & Vořechovský, I. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm680 · Cited by 70 · see citing works
Mammalian 3α-hydroxysteroid dehydrogenases
Penning, T. M., Pawlowski, J. E., Schlegel, B. P., Jez, J. M., Lin, H.-K., Hoog, S. S., Bennett, M. J., & Lewis, M. (1996) · Steroids · doi:10.1016/s0039-128x(96)00093-1 · Cited by 64 · see citing works
Jin, Y., & Penning, T. M. (2006) · Biochemistry · doi:10.1021/bi060591r · Cited by 60 · see citing works
Identification of tunnels in proteins, nucleic acids, inorganic materials and molecular ensembles
Damborský, J., Petřek, M., Banáš, P., & Otyepka, M. (2006) · Biotechnology Journal · doi:10.1002/biot.200600208 · Cited by 59 · see citing works
Nahoum, V., Gangloff, A., Legrand, P., Zhu, D., Cantin, L., Zhorov, B. S., Luu-The, V., Labrie, F., Breton, R., & Lin, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105610200 · Cited by 59 · see citing works
Qin, K.-N., New, M. I., & Cheng, K.-C. (1993) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(93)90308-j · Cited by 53 · see citing works
Wilson, J. D., George, F. W., Shaw, G., & Renfree, M. B. (1999) · Biology of Reproduction · doi:10.1095/biolreprod61.2.471 · Cited by 32 · see citing works
Couture, J., de Jesus-Tran, K. P., Roy, A., Cantin, L., Côté, P., Legrand, P., Luu‐The, V., Labrie, F., & Breton, R. (2005) · Protein Science · doi:10.1110/ps.051353205 · Cited by 29 · see citing works
Vollmer, M., Jung, M., Rüschendorf, F., Ruf, R. G., Wienker, T. F., Reis, A., Krapf, R., & Hildebrandt, F. (1998) · The American Journal of Human Genetics · doi:10.1086/302162 · Cited by 25 · see citing works
Khanna, M., Qin, K., Klisak, I. J., Belkin, S., Sparkes, R. S., & Cheng, K.-C. (1995) · Genomics · doi:10.1016/0888-7543(95)80066-u · Cited by 23 · see citing works
Clinical Implications of Androgen Synthesis via 5&agr;-Reduced Precursors
Ghayee, H. K., & Auchus, R. J. (2008) · KARGER eBooks · doi:10.1159/000134780 · Cited by 20 · see citing works
8 Niacin: Nicotinic Acid, Nicotinamide, NAD(P)
(1988) · De Gruyter eBooks · doi:10.1515/9783110859188.475 · Cited by 6 · see citing works
Flagged first, then by citations
2 of the 74 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Congenital adrenal hyperplasia
El-Maouche, D., Arlt, W., & Merke, D. P. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31431-9 · Cited by 669 · see citing works
Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
Claahsen - van der Grinten, H. L., Speiser, P. W., Ahmed, S. F., Arlt, W., Auchus, R. J., Falhammar, H., Flück, C. E., Guasti, L., Huebner, A., Kortmann, B. B. M., et al. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab016 · Cited by 556 · see citing works
Self-citationThe aldo-keto reductases (AKRs): Overview
Penning, T. M. (2014) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2014.09.024 · Cited by 547 · see citing works
Paediatric and adult-onset male hypogonadism
Salonia, A., Rastrelli, G., Hackett, G., Seminara, S. B., Huhtaniemi, I. T., Rey, R. A., Hellstrom, W. J. G., Palmert, M. R., Corona, G., Dohle, G. R., et al. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0087-y · Cited by 286 · see citing works
NADPH P450 oxidoreductase: Structure, function, and pathology of diseases
Pandey, A. V., & Flück, C. E. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.010 · Cited by 279 · see citing works
Self-citationContribution of Leydig and Sertoli Cells to Testosterone Production in Mouse Fetal Testes
Shima, Y., Miyabayashi, K., Haraguchi, S., Arakawa, T., Otake, H., Baba, T., Matsuzaki, S., Shishido, Y., Akiyama, H., Tachibana, T., et al. (2012) · Molecular Endocrinology · doi:10.1210/me.2012-1256 · Cited by 274 · see citing works
Steroidogenesis: Unanswered Questions
Miller, W. L. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2017.09.002 · Cited by 226 · see citing works
Self-citationRole of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism
Rižner, T. L., & Penning, T. M. (2014) · Steroids · doi:10.1016/j.steroids.2013.10.012 · Cited by 217 · see citing works
Basics of androgen synthesis and action
Elzenaty, R. N., du Toit, T., & Flück, C. E. (2022) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2022.101665 · Cited by 204 · see citing works
Self-citationWitchel, S. F. (2017) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2017.11.005 · Cited by 198 · see citing works
Kamrath, C., Hochberg, Z., Hartmann, M. F., Remer, T., & Wudy, S. A. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1997 · Cited by 191 · see citing works
Management of disorders of sex development
Hiort, O., Birnbaum, W., Marshall, L., Wünsch, L., Werner, R., Schröder, T., Döhnert, U., & Holterhus, P. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.108 · Cited by 181 · see citing works
Alternative (backdoor) androgen production and masculinization in the human fetus
O’Shaughnessy, P. J., Antignac, J. P., Le Bizec, B., Morvan, M.-L., Svechnikov, K., Söder, O., Savchuk, I., Monteiro, A., Soffientini, U., Johnston, Z. C., et al. (2019) · PLOS Biology · doi:10.1371/journal.pbio.3000002 · Cited by 177 · see citing works
Morphological and functional maturation of Leydig cells: from rodent models to primates
Teerds, K. J., & Huhtaniemi, I. T. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmv008 · Cited by 174 · see citing works
Structural and functional biology of aldo-keto reductase steroid transforming enzymes
Penning, T. M., Wangtrakuldee, P., & Auchus, R. J. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00089 · Cited by 164 · see citing works
Normal and Premature Adrenarche
Rosenfield, R. L. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab009 · Cited by 163 · see citing works
DSDs: genetics, underlying pathologies and psychosexual differentiation
Arboleda, V. A., Sandberg, D. E., & Vilain, E. J. N. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.130 · Cited by 158 · see citing works
NADPH–Cytochrome P450 Oxidoreductase: Roles in Physiology, Pharmacology, and Toxicology
Riddick, D. S., Ding, X., Wolf, C. R., Porter, T. D., Pandey, A. V., Zhang, Q., Gu, J., Finn, R. D., Ronseaux, S., McLaughlin, L. A., et al. (2012) · Drug Metabolism and Disposition · doi:10.1124/dmd.112.048991 · Cited by 145 · see citing works
Self-citationThe syndrome of 17,20 lyase deficiency
Miller, W. L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2161 · Cited by 143 · see citing works
Self-citationA new dawn for androgens: novel lessons from 11-oxygenated C19 steroids
Pretorius, E., Arlt, W., & Storbeck, K.-H. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.08.014 · Cited by 142 · see citing works
MECHANISMS IN ENDOCRINOLOGY: Rare defects in adrenal steroidogenesis
Miller, W. L. (2018) · European Journal of Endocrinology · doi:10.1530/eje-18-0279 · Cited by 138 · see citing works
Self-citationRoelofs, M. J. E., van den Berg, M., Bovee, T. F. H., Piersma, A. H., & van Duursen, M. B. M. (2015) · Toxicology · doi:10.1016/j.tox.2015.01.003 · Cited by 137 · see citing works
Understanding the genetic aetiology in patients with XY DSD
Ahmed, S. F., Bashamboo, A., Lucas-Herald, A. K., & McElreavey, K. (2013) · British Medical Bulletin · doi:10.1093/bmb/ldt008 · Cited by 131 · see citing works
Bhargava, A., Arnold, A. P., Bangasser, D. A., Denton, K. M., Gupta, A., Hilliard Krause, L. M., Mayer, E. A., McCarthy, M., Miller, W. L., Raznahan, A., et al. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnaa034 · Cited by 130 · see citing works
Self-citationHuang, Z., Sun, S., Lee, M., Maslov, A. Y., Shi, M., Waldman, S., Marsh, A., Siddiqui, T., Dong, X., Peter, Y., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01035-w · Cited by 125 · see citing works
Fukami, M., Homma, K., Hasegawa, T., & Ogata, T. (2013) · Developmental Dynamics · doi:10.1002/dvdy.23892 · Cited by 114 · see citing works
Steroidogenesis of the testis – new genes and pathways
Flück, C. E., & Pandey, A. V. (2014) · Annales d Endocrinologie · doi:10.1016/j.ando.2014.03.002 · Cited by 113 · see citing works
Self-citationAndrogens and the masculinization programming window: human–rodent differences
Sharpe, R. M. (2020) · Biochemical Society Transactions · doi:10.1042/bst20200200 · Cited by 113 · see citing works
Ahmed, S. F., Achermann, J. C., Alderson, J., Crouch, N. S., Elford, S., Hughes, I. A., Krone, N. P., McGowan, R., Mushtaq, T., O’Toole, S., et al. (2021) · Clinical Endocrinology · doi:10.1111/cen.14528 · Cited by 113 · see citing works
Overview of AKR1C3: Inhibitor Achievements and Disease Insights
Liu, Y., He, S., Chen, Y., Liu, Y., Feng, F., Liu, W., Guo, Q., Zhao, L., & Sun, H. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b02138 · Cited by 105 · see citing works
Mutations of protocadherin 19 in female epilepsy (PCDH19-FE) lead to allopregnanolone deficiency
Tan, C., Shard, C., Ranieri, E., Hynes, K., Pham, D., Leach, D. A., Buchanan, G., Corbett, M. A., Shoubridge, C., Kumar, R., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv245 · Cited by 99 · see citing works
The steroid metabolome of adrenarche
Rege, J., & Rainey, W. E. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0183 · Cited by 97 · see citing works
Pharmacogenomics of human P450 oxidoreductase
Pandey, A. V., & Sproll, P. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00103 · Cited by 92 · see citing works
Self-citationAKR1C1 Activates STAT3 to Promote the Metastasis of Non-Small Cell Lung Cancer
Zhu, H., CHANG, L.-L., Yan, F., Hu, Y. W., Zeng, C., Zhou, T., Yuan, T., Ying, M., Cao, J., He, Q., et al. (2017) · Theranostics · doi:10.7150/thno.21463 · Cited by 92 · see citing works
What Does AMH Tell Us in Pediatric Disorders of Sex Development?
Josso, N., & Rey, R. A. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00619 · Cited by 89 · see citing works
The differential role of androgens in early human sex development
Hiort, O. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-152 · Cited by 87 · see citing works
The “backdoor pathway” of androgen synthesis in human male sexual development
Miller, W. L., & Auchus, R. J. (2019) · PLoS Biology · doi:10.1371/journal.pbio.3000198 · Cited by 84 · see citing works
Self-citationAndrogens During Infancy, Childhood, and Adolescence: Physiology and Use in Clinical Practice
Mason, K. A., Schoelwer, M. J., & Rogol, A. D. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa003 · Cited by 82 · see citing works
P450 Oxidoreductase deficiency: Analysis of mutations and polymorphisms
Burkhard, F. Z., Parween, S., Udhane, S. S., Flück, C. E., & Pandey, A. V. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.04.003 · Cited by 79 · see citing works
Self-citationMonogenic disorders of adrenal steroidogenesis
Baranowski, E. S., Arlt, W., & Idkowiak, J. (2018) · Hormone Research in Paediatrics · doi:10.1159/000488034 · Cited by 79 · see citing works
Copy Number Variation in the Horse Genome
Ghosh, S., Qu, Z., Das, P. J., Fang, E., Juras, R., Cothran, E. G., McDonell, S., Kenney, D. G., Lear, T. L., Adelson, D. L., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004712 · Cited by 78 · see citing works
Marti, N., Galván, J. A., Pandey, A. V., Trippel, M., Tapia, C., Müller, M., Perren, A., & Flück, C. E. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.07.029 · Cited by 76 · see citing works
Self-citationOf marsupials and men: “Backdoor” dihydrotestosterone synthesis in male sexual differentiation
Biason-Lauber, A., Miller, W. L., Pandey, A. V., & Flück, C. E. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.01.017 · Cited by 69 · see citing works
Self-citationWang, J., Li, Z., & Yang, W.-X. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.838858 · Cited by 69 · see citing works
The next 150 years of congenital adrenal hyperplasia
Turcu, A. F., & Auchus, R. J. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.05.013 · Cited by 69 · see citing works
The Role of Androgen Signaling in Male Sexual Development at Puberty
Rey, R. A. (2020) · Endocrinology · doi:10.1210/endocr/bqaa215 · Cited by 66 · see citing works
Adrenal cortex development and related disorders leading to adrenal insufficiency
Pignatti, E., & Flück, C. E. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111206 · Cited by 63 · see citing works
Self-citationFan, Y., Zhang, X., Wang, L., Wang, R., Huang, Z., Sun, Y., Yao, R., Huang, X., Ye, J., Han, L., et al. (2017) · Scientific Reports · doi:10.1038/srep44536 · Cited by 61 · see citing works
Steroid Hormones and the Development of Reproductive Organs
Morohashi, K.-I., Baba, T., & Tanaka, M. (2012) · Sexual Development · doi:10.1159/000342272 · Cited by 60 · see citing works
Baronio, F., Ortolano, R., Menabò, S., Cassio, A., Baldazzi, L., Natale, V. D., Tonti, G., Vestrucci, B., & Balsamo, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184605 · Cited by 59 · see citing works
Inverted Low-Copy Repeats and Genome Instability-A Genome-Wide Analysis
Dittwald, P., Gambin, T., Gonzaga-Jauregui, C. G., Carvalho, C. M. B., Lupski, J. R., Stankiewicz, P., & Gambin, A. (2012) · Human Mutation · doi:10.1002/humu.22217 · Cited by 58 · see citing works
Malíková, J., Brixius‐Anderko, S., Udhane, S. S., Parween, S., Dick, B., Bernhardt, R., & Pandey, A. V. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2017.09.007 · Cited by 58 · see citing works
Self-citationRevisiting Steroidogenic Pathways in the Human Placenta and Primary Human Trophoblast Cells
Karahoda, R., Kallol, S., Groessl, M., Ontsouka, E. C., Anderle, P., Flück, C. E., Štaud, F., & Albrecht, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041704 · Cited by 55 · see citing works
Self-citationEmerging concepts on Leydig cell development in fetal and adult testis
Bhattacharya, I., & Dey, S. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1086276 · Cited by 55 · see citing works
Leydig progenitor cells in fetal testis
Shima, Y., & Morohashi, K.-I. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.12.006 · Cited by 55 · see citing works
A guide to understanding the steroid pathway: New insights and diagnostic implications
Greaves, R. F., Jevalikar, G., Hewitt, J. K., & Zacharin, M. (2014) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2014.07.017 · Cited by 53 · see citing works
Rebourcet, D., Mackay, R., Darbey, A. L., Curley, M. K., Jørgensen, A., Frederiksen, H. W., Mitchell, R. T., O’Shaughnessy, P. J., Nef, S., & Smith, L. B. (2020) · The FASEB Journal · doi:10.1096/fj.202000361r · Cited by 52 · see citing works
The Adrenal Cortex and its Disorders
Miller, W. L. (2009) · Wiley eBooks · doi:10.1002/9781444316728.ch13 · Cited by 51 · see citing works
Self-citationDevelopment and function of the fetal adrenal
Pignatti, E., du Toit, T., & Flück, C. E. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-022-09756-3 · Cited by 50 · see citing works
Self-citationBremer, A. A., & Miller, W. L. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-408134-5.00013-5 · Cited by 50 · see citing works
Self-citationDhayat, N. A., Dick, B., Frey, B. M., d’Uscio, C. H., Vogt, B., & Flück, C. E. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.07.009 · Cited by 50 · see citing works
Self-citationNew Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice
Lawrence, B. M., O’Donnell, L., Smith, L. B., & Rebourcet, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415555 · Cited by 47 · see citing works
Dhayat, N. A., Marti, N., Kollmann, Z., Troendle, A., Bally, L., Escher, G., Groessl, M., Ackermann, D., Ponte, B., Pruijm, M. T., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203903 · Cited by 46 · see citing works
Self-citationA brief history of adrenal research
Miller, W. L. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.10.023 · Cited by 44 · see citing works
Self-citationAndrogen biosynthesis in castration-resistant prostate cancer
Penning, T. M. (2014) · Endocrine Related Cancer · doi:10.1530/erc-14-0109 · Cited by 44 · see citing works
Fernández‐Cancio, M., Camats, N., Flück, C. E., Zalewski, A., Dick, B., Frey, B. M., Monné, R., Torán, N., Audı́, L., & Pandey, A. V. (2018) · Pharmaceuticals · doi:10.3390/ph11020037 · Cited by 44 · see citing works
Self-citationFertility Issues in Disorders of Sex Development
Guercio, G., Costanzo, M., Grinspon, R. P., & Rey, R. A. (2015) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2015.07.012 · Cited by 43 · see citing works
Addressing gaps in care of people with conditions affecting sex development and maturation
on behalf of COST Actions DSDnet and GnRH Network as well as the European Reference Network for Rare Endocrine Conditions (Endo–ERN), Hiort, O., Cools, M., Springer, A., McElreavey, K., Greenfield, A., Wudy, S. A., Kulle, A. E., Ahmed, S. F., Dessens, A. B., et al. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0238-y · Cited by 43 · see citing works
Adrenal cortex and its disorders
Miller, W. L., & Flück, C. E. (2014) · Elsevier eBooks · doi:10.1016/b978-1-4557-4858-7.00022-6 · Cited by 43 · see citing works
Self-citationAndrogen Metabolism and Response in Prostate Cancer Anti-Androgen Therapy Resistance
Zhang, H., Yi, Z., Xing, Z., Sah, R. K., Hu, J., & Hu, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113521 · Cited by 42 · see citing works
Engeli, R. T., Fürstenberger, C., Kratschmar, D. V., & Odermatt, A. (2018) · Heliyon · doi:10.1016/j.heliyon.2018.e00527 · Cited by 42 · see citing works
Postnatal Testicular Activity in Healthy Boys and Boys With Cryptorchidism
Kuiri‐Hänninen, T., Koskenniemi, J. J., Dunkel, L., Toppari, J., & Sankilampi, U. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00489 · Cited by 41 · see citing works
Fetal endocrine therapy for congenital adrenal hyperplasia should not be done
Miller, W. L. (2015) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2015.01.005 · Cited by 40 · see citing works
Self-citationWitchel, S. F., & Topaloglu, A. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-47912-7.00017-2 · Cited by 40 · see citing works
Zhu, H., Liu, W., Han, B., Fan, M., Zhao, S., Wang, H., Lu, Y., Pan, C., Chen, F., Chen, M., et al. (2014) · Clinical Endocrinology · doi:10.1111/cen.12456 · Cited by 40 · see citing works
Diagnosis and Treatment of Disorders of Sexual Development
Rey, R. A., & Josso, N. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00119-0 · Cited by 40 · see citing works
Yatsenko, S. A., & Witchel, S. F. (2017) · Seminars in Perinatology · doi:10.1053/j.semperi.2017.03.016 · Cited by 39 · see citing works
van Rooyen, D., Gent, R., Barnard, L., & Swart, A. C. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2017.12.014 · Cited by 39 · see citing works
P450 Enzymes in Steroid Processing
Auchus, R. J., & Miller, W. L. (2015) · Springer eBooks · doi:10.1007/978-3-319-12108-6_12 · Cited by 39 · see citing works
Self-citationFlück, C. E., Mallet, D., Hofer, G., Samara‐Boustani, D., Léger, J., Polak, M., Morel, Y., & Pandey, A. V. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.08.001 · Cited by 39 · see citing works
Self-citationImpact on CYP19A1 activity by mutations in NADPH cytochrome P450 oxidoreductase
Flück, C. E., & Pandey, A. V. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.03.031 · Cited by 39 · see citing works
Self-citationParween, S., Roucher-Boulez, F., Flück, C. E., Lienhardt-Roussie, A., Mallet, D., Morel, Y., & Pandey, A. V. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1928 · Cited by 37 · see citing works
Self-citationGuidelines for diagnosis and treatment of 21-hydroxylase deficiency (2014 revision)
Ishii, T., Anzo, M., Adachi, M., Onigata, K., Kusuda, S., Nagasaki, K., Harada, S., Horikawa, R., Minagawa, M., Minamitani, K., et al. (2015) · Clinical Pediatric Endocrinology · doi:10.1297/cpe.24.77 · Cited by 36 · see citing works
Translating genomics to the clinical diagnosis of disorders/differences of sex development
Parivesh, A., Barseghyan, H., Délot, E. C., & Vilain, E. J. N. (2019) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2019.01.005 · Cited by 36 · see citing works
Classic and backdoor pathways of androgen biosynthesis in human sexual development
Lee, H. G., & Kim, C. J. (2022) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2244124.062 · Cited by 32 · see citing works
Byers, H. M., Mohnach, L. H., Fechner, P. Y., Chen, M., Thomas, I. H., Ramsdell, L. A., Shnorhavorian, M., McCauley, E., Oelschlager, A. A., Park, J. M., et al. (2017) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.31560 · Cited by 32 · see citing works
History of Adrenal Research: From Ancient Anatomy to Contemporary Molecular Biology
Miller, W. L., & White, P. C. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac019 · Cited by 31 · see citing works
Self-citationSix Decades of Research on Human Fetal Gonadal Steroids
Connan-Perrot, S., Léger, T., Lelandais, P., Lethimonier, C., David, A., Fowler, P., & Mazaud‐Guittot, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136681 · Cited by 30 · see citing works
Development of the human fetal testis
O’Shaughnessy, P. J., & Fowler, P. (2014) · Annales d Endocrinologie · doi:10.1016/j.ando.2014.03.009 · Cited by 29 · see citing works
Differences of sex development
Ahmed, S. F., Armstrong, K., Cheng, E. Y., Cools, M., Harley, V. R., Mendonca, B. B., Nordenström, A., Rey, R. A., Sandberg, D. E., Utari, A., et al. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-025-00637-y · Cited by 28 · see citing works
Self-citationPubertal orchestration of hormones and testis in primates
Bhattacharya, I., Sharma, S. S., & Majumdar, S. S. (2019) · Molecular Reproduction and Development · doi:10.1002/mrd.23246 · Cited by 28 · see citing works
Fertility Issues in the Management of Patients with Disorders of Sex Development
Guercio, G., & Rey, R. A. (2014) · Endocrine development · doi:10.1159/000363633 · Cited by 28 · see citing works
Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH
Gregorio, E. D., Savin, E., Biamino, E., Belligni, E. F., Naretto, V. G., D′Alessandro, G., Gai, G., Fiocchi, F., Calcia, A., Mancini, C., et al. (2014) · Molecular Cytogenetics · doi:10.1186/s13039-014-0082-7 · Cited by 28 · see citing works
Fowler, P., Filis, P., Bhattacharya, S., Bizec, B. L., Antignac, J., Morvan, M., Drake, A. J., Soffientini, U., & O’Shaughnessy, P. J. (2016) · Human Reproduction · doi:10.1093/humrep/dev323 · Cited by 27 · see citing works
Parween, S., Fernández‐Cancio, M., Benito‐Sanz, S., Camats, N., Velazquez, M. N. R., López‐Siguero, J., Udhane, S. S., Kagawa, N., Flück, C. E., Audı́, L., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa076 · Cited by 27 · see citing works
Self-citationAlteration of the steroidogenesis in boys with autism spectrum disorders
Janšáková, K., Hill, M., Čelárová, D., Celušáková, H., Repiská, G., Bičı́ková, M., Máčová, L., & Ostatníková, D. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-01017-8 · Cited by 26 · see citing works
Wisniewski, A. B. (2012) · Scientifica · doi:10.6064/2012/834967 · Cited by 26 · see citing works
Aldo-keto reductase (AKR) superfamily website and database: An update
Huacachino, A. A., Joo, J., Narayanan, N., Tehim, A., Himes, B. E., & Penning, T. M. (2024) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2024.111111 · Cited by 25 · see citing works
van Rooyen, D., Yadav, R., Scott, E. E., & Swart, A. C. (2020) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2020.105614 · Cited by 25 · see citing works
Donohoue, P. A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-76174-1.00026-2 · Cited by 24 · see citing works
- Authors
- Flück, C. E., Meyer-Böni, M., Pandey, A. V., Kempná, P., Miller, W. L., Schoenle, E. J., & Biason-Lauber, A.
- Affiliations
- University of Bern (CH)
- University of California, San Francisco (US)
- University Children's Hospital Zurich (CH)
- Corresponding author
- Flück, Christa E.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 89
- Issue
- 2
- Pages
- 201-218
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC3155178
- OpenAlex
- W2066296351
- Semantic Scholar
- 35d55145faae3af26a68bab9da7255b0b7db12d0
- Cited by
- 248
- References
- 74
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 11 · 2023: 14 · 2022: 22 · 2021: 26 · 2020: 21 · 2019: 17 · 2018: 16 · 2017: 19 · 2016: 18 · 2015: 16 · 2014: 25 · 2013: 13 · 2012: 12
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-08-12)
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (130710)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- AKR1C2, AKR1C4, dihydrotestosterone, male sexual differentiation, 46,XY disorders of sex development, enzyme activity, aberrant splicing, candidate gene identification
- MeSH terms
- Amino Acid Sequence, Androgens, Base Sequence, Family, Female, Fetus, Gene Expression Regulation, Humans, Hydroxysteroid Dehydrogenases, Male, Models, Molecular, Molecular Sequence Data, Mutation, Oxidoreductases, Pedigree, Sex Differentiation, Dihydrotestosterone, Testis, Alternative Splicing, Gene Expression Profiling, 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific), Mutant Proteins, Biosynthetic Pathways
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
