This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Hughes, I. A. Search for Related Content PubMed PubMed Citation Articles by Hughes, I. A.

Minireview: Sex Differentiation

Department of Paediatrics, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom

Address all correspondence and requests for reprints to: Ieuan A. Hughes, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Department of Pediatrics, Hills Road, Box 116, Cambridge CB2 2QQ, United Kingdom. E-mail: iah1000{at}cam.ac.uk

Mammalian sex differentiation is a hormone-dependent process in the male following the determination of a testis from the indifferent gonad through a cascade of genetic events. Female sex differentiation is not dependent on ovarian hormones, yet there is evidence that members of the Wnt family of developmental signaling molecules play a role in Müllerian duct development and in suppressing Leydig cell differentiation in the ovary. The testis induces male sex differentiation (including testis descent) through a time-dependent production of optimal concentrations of anti-Müllerian hormone, insulin-like factor(s) and androgens. Observations in several human syndromes of disordered fetal sex development corroborate findings in murine embryo studies, although there are exceptions in some gene knockout models. The ubiquitously expressed AR interacts in a ligand-dependent manner with coregulators to control the expression of androgen-responsive genes. Preliminary studies suggest the possibility of hormone resistance syndromes associated with coregulator dysfunction. Polymorphic variants in genes controlling androgen synthesis and action may modulate androgenic effects on sex differentiation.

This article has been cited by other articles:

				K Raghuveer and B Senthilkumaran Identification of multiple dmrt1s in catfish: localization, dimorphic expression pattern, changes during testicular cycle and after methyltestosterone treatment J. Mol. Endocrinol., May 1, 2009; 42(5): 437 - 448. [Abstract] [Full Text] [PDF]

				P. A. Fowler, D. R. Abramovich, N. E. Haites, P. Cash, N. P. Groome, A. Al-Qahtani, T. J. Murray, and R. G. Lea Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations Hum. Reprod., November 1, 2007; 22(11): 2919 - 2927. [Abstract] [Full Text] [PDF]

				H.-S. Chang, M. D. Anway, S. S. Rekow, and M. K. Skinner Transgenerational Epigenetic Imprinting of the Male Germline by Endocrine Disruptor Exposure during Gonadal Sex Determination Endocrinology, December 1, 2006; 147(12): 5524 - 5541. [Abstract] [Full Text] [PDF]

				M. Metta, R. Gudavalli, J.-M. Gibert, and C. Schlotterer No Accelerated Rate of Protein Evolution in Male-Biased Drosophila pseudoobscura Genes Genetics, September 1, 2006; 174(1): 411 - 420. [Abstract] [Full Text] [PDF]

				X. Yang, E. E. Schadt, S. Wang, H. Wang, A. P. Arnold, L. Ingram-Drake, T. A. Drake, and A. J. Lusis Tissue-specific expression and regulation of sexually dimorphic genes in mice Genome Res., August 1, 2006; 16(8): 995 - 1004. [Abstract] [Full Text] [PDF]

				S. W. Grande, A. J. M. Andrade, C. E. Talsness, K. Grote, and I. Chahoud A Dose-Response Study Following In Utero and Lactational Exposure to Di(2-ethylhexyl)phthalate: Effects on Female Rat Reproductive Development Toxicol. Sci., May 1, 2006; 91(1): 247 - 254. [Abstract] [Full Text] [PDF]

				K. A. L. Tan, K. De Gendt, N. Atanassova, M. Walker, R. M. Sharpe, P. T. K. Saunders, E. Denolet, and G. Verhoeven The Role of Androgens in Sertoli Cell Proliferation and Functional Maturation: Studies in Mice with Total or Sertoli Cell-Selective Ablation of the Androgen Receptor Endocrinology, June 1, 2005; 146(6): 2674 - 2683. [Abstract] [Full Text] [PDF]

				S. E. Hannema, I. S. Scott, J. Hodapp, H. Martin, N. Coleman, J. W. Schwabe, and I. A. Hughes Residual Activity of Mutant Androgen Receptors Explains Wolffian Duct Development in the Complete Androgen Insensitivity Syndrome J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5815 - 5822. [Abstract] [Full Text] [PDF]

				A. Umar, M. P. Ooms, T. M. Luider, J. A. Grootegoed, and A. O. Brinkmann Proteomic Profiling of Epididymis and Vas Deferens: Identification of Proteins Regulated during Rat Genital Tract Development Endocrinology, October 1, 2003; 144(10): 4637 - 4647. [Abstract] [Full Text] [PDF]

				K. Nishimura, H.-J. Ting, Y. Harada, T. Tokizane, N. Nonomura, H.-Y. Kang, H.-C. Chang, S. Yeh, H. Miyamoto, M. Shin, et al. Modulation of Androgen Receptor Transactivation by Gelsolin: A Newly Identified Androgen Receptor Coregulator Cancer Res., August 15, 2003; 63(16): 4888 - 4894. [Abstract] [Full Text] [PDF]

				C. Crescioli, M. Maggi, G. B. Vannelli, P. Ferruzzi, S. Granchi, R. Mancina, M. Muratori, G. Forti, M. Serio, and M. Luconi Expression of Functional Estrogen Receptors in Human Fetal Male External Genitalia J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1815 - 1824. [Abstract] [Full Text] [PDF]

				A. Umar, T. M. Luider, C. A. Berrevoets, J. A. Grootegoed, and A. O. Brinkmann Proteomic Analysis of Androgen-Regulated Protein Expression in a Mouse Fetal Vas Deferens Cell Line Endocrinology, April 1, 2003; 144(4): 1147 - 1154. [Abstract] [Full Text] [PDF]