This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hasegawa, T. Articles by Ogata, T. Search for Related Content PubMed PubMed Citation Articles by Hasegawa, T. Articles by Ogata, T.

Testicular Dysgenesis without Adrenal Insufficiency in a 46,XY Patient with a Heterozygous Inactive Mutation of Steroidogenic Factor-1

Department of Pediatrics, Keio University School of Medicine (T.H., G.S.), Tokyo 160-8582, Japan; Department of Urology, Asoka Hospital (K.F.), Tokyo 135-0002, Japan; Division of Cell Differentiation, National Institute for Basic Biology (K.-I.M.), Okazaki 444-8585, Japan; and Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development (M.F., N.S., N.K., T.O.), Tokyo 154-8567, Japan

Address all correspondence and requests for reprints to: Dr. Tsutomu Ogata, Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya, Tokyo 154-8567, Japan. E-mail: tomogata{at}nch.go.jp.

Steroidogenic factor-1 (SF-1) regulates multiple genes involved in the adrenal and gonadal development and in the biosynthesis of a variety of hormones, including adrenal and gonadal steroids, anti-Mullerian hormone (AMH), and gonadotropins. We identified a novel SF-1 mutation in a 27-yr-old Japanese patient with a 46,XY karyotype. Sequence analysis was performed for all the seven exons of SF-1, revealing a heterozygous single base pair deletion at exon 2 (18delC) that is predicted to cause a frameshift at the sixth codon and resultant termination at the 74th codon. Functional studies showed that the mutation produced no demonstrable protein and had no transcription activity or dominant negative effect. Clinical features included small dysgenetic testes with vasa deferentia and epididymides, absent uterus, blind-ending vagina, clitoromegaly, and psychosexual disturbance. Endocrine studies showed normal adrenal function (cortisol response to ACTH stimulation, 13.425.3 µg/dl) and primary hypogonadism (testosterone response to hCG stimulation, 0.570.76 ng/ml; gonadotropin responses to GnRH stimulation: LH, 1059 mIU/ml; FSH, 3669 mIU/ml), and urinary steroid hormone profile analysis indicated grossly normal steroidogenic enzyme activities. The results suggest that SF-1 haploinsufficiency can selectively impair testicular development and permit the biosynthesis of AMH and testosterone in dysgenetic testes and the production of gonadotropins in pituitary gonadotropes.

This article has been cited by other articles:

				P. Philibert, D. Zenaty, L. Lin, S. Soskin, F. Audran, J. Leger, J. C. Achermann, and C. Sultan Mutational analysis of steroidogenic factor 1 (NR5a1) in 24 boys with bilateral anorchia: a French collaborative study Hum. Reprod., December 1, 2007; 22(12): 3255 - 3261. [Abstract] [Full Text] [PDF]

				A. L Reuter, K. Goji, N. C Bingham, M. Matsuo, and K. L Parker A novel mutation in the accessory DNA-binding domain of human steroidogenic factor 1 causes XY gonadal dysgenesis without adrenal insufficiency Eur. J. Endocrinol., August 1, 2007; 157(2): 233 - 238. [Abstract] [Full Text] [PDF]

				R. Coutant, D. Mallet, N. Lahlou, N. Bouhours-Nouet, A. Guichet, L. Coupris, A. Croue, and Y. Morel Heterozygous Mutation of Steroidogenic Factor-1 in 46,XY Subjects May Mimic Partial Androgen Insensitivity Syndrome J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 2868 - 2873. [Abstract] [Full Text] [PDF]

				L. Lin, P. Philibert, B. Ferraz-de-Souza, D. Kelberman, T. Homfray, A. Albanese, V. Molini, N. J. Sebire, S. Einaudi, G. S. Conway, et al. Heterozygous Missense Mutations in Steroidogenic Factor 1 (SF1/Ad4BP, NR5A1) Are Associated with 46,XY Disorders of Sex Development with Normal Adrenal Function J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 991 - 999. [Abstract] [Full Text] [PDF]

				L. Lin, W.-X. Gu, G. Ozisik, W. S. To, C. J. Owen, J. L. Jameson, and J. C. Achermann Analysis of DAX1 (NR0B1) and Steroidogenic Factor-1 (NR5A1) in Children and Adults with Primary Adrenal Failure: Ten Years' Experience J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3048 - 3054. [Abstract] [Full Text] [PDF]

				M. Zubair, S. Ishihara, S. Oka, K. Okumura, and K.-i. Morohashi Two-Step Regulation of Ad4BP/SF-1 Gene Transcription during Fetal Adrenal Development: Initiation by a Hox-Pbx1-Prep1 Complex and Maintenance via Autoregulation by Ad4BP/SF-1. Mol. Cell. Biol., June 1, 2006; 26(11): 4111 - 4121. [Abstract] [Full Text] [PDF]

				J. N. Winnay, J. Xu, B. W. O'Malley, and G. D. Hammer Steroid Receptor Coactivator-1-Deficient Mice Exhibit Altered Hypothalamic-Pituitary-Adrenal Axis Function Endocrinology, March 1, 2006; 147(3): 1322 - 1332. [Abstract] [Full Text] [PDF]

				J. L. Jameson Of Mice and Men: The Tale of Steroidogenic Factor-1 J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 5927 - 5929. [Full Text] [PDF]