RESUMO
During a 10-year period 65 children and adolescents with ambiguous genitalia from the Dominican Republic, not known through kindred studies of 5 alpha-reductase deficiency, were evaluated. Plasma androgen determinations were performed before and/or after Leydig cell stimulation of the testes with human chorionic gonadotropin. Of the children there were 24 female pseudohermaphrodites, 21 of whom had 21-hydroxylase deficiency, 1 true hermaphrodite and 40 (62 per cent) male pseudohermaphrodites. One child had a human chorionic gonadotropin response suggestive of 17-20 desmolase deficiency, and on further evaluation he also had partial deficiencies of the enzymes 21-hydroxylase and 17 alpha-hydroxylase. Five subjects had a female phenotype and subnormal androgen responses to human chorionic gonadotropin. In 5 of 33 male pseudohermaphrodites with a normal testosterone response to human chorionic gonadotropin 5 alpha-reductase deficiency was suspected by elevated plasma testosterone/dihydrotestosterone ratios before and/or after human chorionic gonadotropin stimulation. The diagnosis of 5 alpha-reductase deficiency was confirmed by elevated 5 beta/5 alpha urinary C19 and C21 steroid metabolite ratios. One subject with 5 alpha-reductase deficiency was traced to the original Dominican kindred of 38 affected subjects. Pedigree analysis of another proband revealed 3 additional affected relatives. Four subjects with a normal testosterone response to human chorionic gonadotropin had XO/XY gonadal dysgenesis. There were 25 male pseudohermaphrodites with normal plasma testosterone and dihydrotestosterone responses to human chorionic gonadotropin, who were not diagnosed by this methodology. This study reveals that 5 alpha-reductase deficiency occurs with a frequency of 13 per cent as a cause of male pseudohermaphroditism in the Dominican Republic with approximately the same frequency as XO/XY gonadal dysgenesis. Unlike female pseudohermaphrodites, the majority of male subjects with pseudohermaphroditism remain unclassified by these techniques.
Assuntos
Transtornos do Desenvolvimento Sexual/enzimologia , Disgenesia Gonadal/enzimologia , Oxirredutases/deficiência , Adolescente , Hiperplasia Suprarrenal Congênita , Criança , Colestenona 5 alfa-Redutase , Transtornos do Desenvolvimento Sexual/genética , República Dominicana , Feminino , Genótipo , Disgenesia Gonadal/genética , Humanos , Masculino , Linhagem , Testosterona/sangueRESUMO
To determine the contribution of androgens to the formation of male-gender identity, we studied male pseudohermaphrodites who had decreased dihydrotestosterone production due to 5 alpha-reductase deficiency. These subjects were born with female-appearing external genitalia and were raised as girls. They have plasma testosterone levels in the high normal range, show an excellent response to testosterone and are unique models for evaluating the effect of testosterone, as compared with a female upbringing, in determining gender identity. Eighteen of 38 affected subjects were unambiguously raised as girls, yet during or after puberty, 17 of 18 changed to a male-gender identity and 16 of 18 to a male-gender role. Thus, exposure of the brain to normal levels of testosterone in utero, neonatally and at puberty appears to contribute substantially to the formation of male-gender identity. These subjects demonstrate that in the absence of sociocultural factors that could interrupt the natural sequence of events, the effect of testosterone predominates, over-riding the effect of rearing as girls.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/deficiência , Androgênios/fisiologia , Transtornos do Desenvolvimento Sexual/psicologia , Identidade de Gênero , Identificação Psicológica , Oxirredutases/deficiência , Adolescente , Adulto , Idoso , Criança , Características Culturais , República Dominicana , Humanos , Masculino , Pessoa de Meia-Idade , Puberdade , Papel (figurativo) , Comportamento Sexual , Meio SocialAssuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/deficiência , Transtornos do Desenvolvimento Sexual/genética , Oxirredutases/deficiência , Adulto , Androstano-3,17-diol/urina , Células Cultivadas , Criança , Transtornos do Desenvolvimento Sexual/epidemiologia , República Dominicana , Etiocolanolona/urina , Humanos , Hidroxiesteroides/urina , Cariotipagem , Cetosteroides/urina , Masculino , Linhagem , Esteroides/urina , Síndrome , Testosterona/metabolismoRESUMO
In male pseudohermaphrodites born with ambiguity of the external genitalia but with marked virilization at puberty, biochemical evaluation reveals a marked decrease in plasma dihydrotestosterone secondary to a decrease in steroid 5alpha-reductase activity. In utero the decrease in dihydrotestosterone results in incomplete masculinization of the external genitalia. Inheritance is autosomal recessive.