The rat androgen receptor gene promoter

The androgen receptor (AR) is activated upon binding of testosterone or dihydrotestosterone and exerts regulatory effects on gene expression in androgen target cells. To study transcriptional regulation of the rat AR gene itself, the 5' genomic region of this gene was cloned from a genomic library and the promoter was identified. S1-nuclease protection analysis showed two major transcription start sites, located between 1010 and 1023 bp upstream from the translation initiation codon. The area surrounding these start sites was cloned in both orientations in a CAT reporter plasmid. Upon transfection of the constructs into COS cells, part of the promoter stimulated transcription in an orientation-independent manner, but the full promoter showed a higher and unidirectional activity. In the promoter/reporter gene constructs, transcription initiated from the same positions as in the native gene. Sequence analysis showed that the promoter of the rat AR gene lacks typical TATA and CCAAT box elements, but one SP1 site is located at about 60 bp upstream from the major start site of transcription. Other possible promoter elements are TGTYCT sequences at positions -174 to -179, -434 to -439., -466 to -471, and -500 to -505, resembling half-sites of the glucocorticoid-responsive element (GRE). Furthermore, a homopurine stretch containing a total of 8 GGGGA elements and similar to sequences that are present in several other GC-rich promoters, is located between -89 and -146 bp upstream from the major start site of transcriptio

Estudio citogenético y molecular en personas con conducta transexual

[Resumen]La transexualidad es un desorden de la identidad de género con etiología multifactorial en donde están implicados tanto factores del neurodesarrollo como genéticos. En esta investigación se analizó la vulnerabilidad genética de la transexualidad en un grupo de transexuales FtM (female to male) y MtF (male to female) mediante el estudio del cariotipo y el análisis de cuatro regiones polimórficas de los genes ERβ, AR, CYP19A1 y CYP17A1 en una población de 715 transexuales y 844 controles. Resultados: No se encontró una alteración cariotípica específica de la transexualidad, aunque la aneuploidía fue 4,5 veces mayor en la población transexual (2,4%) que en la población general (0,53%) (p = 1E-06). La prevalencia del síndrome de Klinefelter fue significativamente mayor que la esperada (p = 0,022031). El polimorfismo del ERβ fue significativamente más largo en FtM que en el grupo control femenino (p = 0,002). La probabilidad de desarrollo de la transexualidad fue mayor en los individuos FtM homocigotos LL (odds ratio: 2,001 [1,15-3,46]). El polimorfismo CYP17 MspA1 mostró una distribución alélica dependiente del sexo en la población transexual FtM>MtF (p = 0,041), al contrario que la población control, lo que indica una asociación entre este polimorfismo y la transexualidad.[Resumo]A transexualidade é unha desorde da identidade de xénero con etioloxía multifactorial onde están implicados tanto factores do neurodesenvolvemento coma xenéticos. Nesta investigación analizouse a vulnerabilidade xenética da transexualidade nun grupo de transexuais FtM (female to male) e MtF (male to female), a través do estudo citoxenético do cariotipo e da análise molecular de catro rexións polimórficas dos xenes ERβ, AR, CYP19A1 e CYP17A1 nunha populación de 715 transexuais e 844 controis. Resultados: Non foi encontrada unha alteración cariotípica específica da transexualidade, mais a prevalencia da aneuploidía foi 4,5 veces superior na populación transexual (2,4%) que na populación xeral (0,53%) (p = 1E-06). A síndrome de Klinefelter mostrou unha prevalencia significativamente maior que a esperada (p = 0,022031). Canto á análise molecular, o número de repeticións do polimorfismo ERβ foi significativamente maior en FtM que no grupo control feminino (p = 0,002) e a probabilidade de desenvolvemento da transexualidade foi maior nos individuos FtM homocigotos para o alelo longo (LL) (odds ratio: 2,001 [1,15-3,46]). A respecto do polimorfismo CYP17 MspA1, foi achada unha distribución alélica dependente do sexo FtM>MtF (p = 0,041), ao contrario do que na populación control, o que indica unha asociación entre este polimorfismo e a transexualidade.[Abstract]Transsexualism is a gender identity disorder with a multifactorial etiology. Both neurodevelopmental and genetic factors seem to be implicated. The aim of this study was to investigate the possible influence of genetic factors on the etiology of FtM (female to male) and MtF (male to female) transsexualism by analysing the karyotypes and performing the molecular analysis of four polymorphisms on genes ERβ, AR, CYP19A1 and CYP17A1. We carried out the analysis in 715 transsexuals and 844 controls. Results: No karyotype aberration has been linked to transsexualism but aneuploidy prevalence (2.4%) appears to be higher than in the general population (0.53%) (p = 1E-06). The prevalence of Klinefelter syndrome is also significantly higher (p = 0.022031) than in the general population. FtMs differed from control females with respect to ERβ (p = 0.002). Repeats in ERβ were significantly higher in FtMs than in female controls, and the likelihood of developing transsexualism was higher in the subjects (LL) (odds ratio: 2.001 [1.15-3.46]). Regarding CYP17 MspA1, the allelic frequencies differed significantly between FtMs and MtFs (p = 0.041) but were not sex-dependent in the control population. The data support the association between this polymorphism and transsexualism