title: Sex steroid-related genes and male-to-female transsexualism.
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 ERbeta 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 ERbeta 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.
authors.affiliation: Department of Pharmacology, Institute of Physiology and Pharmacology, Göteborg University, Göteborg, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Henningsson
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Lundström
authors.forename: Lisa
authors.initials: L
authors.lastname: Ekselius
authors.forename: Owe
authors.initials: O
authors.lastname: Bodlund
authors.forename: Eva
authors.initials: E
authors.lastname: Lindström
authors.forename: Monika
authors.initials: M
authors.lastname: Hellstrand
authors.forename: Roland
authors.initials: R
authors.lastname: Rosmond
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
mesh_terms: D000328:Adult; D000483:Alleles; D001141:Aromatase / Q000235:genetics; D004247:DNA / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014189:Transsexualism / Q000235:genetics*
chemical_list: D047629:Estrogen Receptor beta; D012739:Gonadal Steroid Hormones; D004247:DNA; D001141:Aromatase