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Sex steroid-related genes and male-to-female transsexualism

Journal article
Authors Susanne Henningsson
Lars Westberg
Staffan Nilsson
Bengt Lundström
Lisa Ekselius
Owe Bodlund
Eva Lindström
Monika Hellstrand
Roland Rosmond
Elias Eriksson
Mikael Landén
Published in Psychoneuroendocrinology
Volume 30
Issue 7
Pages 657-664
Publication year 2005
Published at Cardiovascular Institute
Department of Mathematical Sciences, Mathematical Statistics
Institute of Physiology and Pharmacology, Dept of Pharmacology
Pages 657-664
Language en
Links dx.doi.org/10.1016/j.psyneuen.2005....
Keywords Aromatase; Androgen receptor; Estrogen receptor beta; Gender identity disorder; Polymorphisms; Sexual differentiation; Transsexualism
Subject categories Medical and Health Sciences

Abstract

Transsexualism is characterised by lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and—after aromatase-catalyzed conversion to estradiol—via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ERβ gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy male controls. Transsexuals differed from controls with respect to the mean length of the ERβ repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.

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