HUMAN PREPUBERTAL AROMATASE DEFICIENCY . PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL LESSONS LEARNED FROM THIS EXPERIMENT OF NATURE

En els humans, el cP450arom es el producte d'un gen unic (CYP19), localitzat en el cromosoma 15q21.1. A la placenta, l'aromatitzacio activa dels androgens protegeix el fetus femella i la mare de les accions virilitzants dels androgens fetals. De fet, els nadons 46XX amb deficiencia completa de l'aromatasa neixen amb una ambiguitat dels genitals externs. Els estudis en pacients afectats per la deficiencia completa del cP450arom han contribuit considerablement a l'analisi de la importancia de l'activitat de la cP450arom en la diferenciacio sexual, en el patro de secrecio de les gonadotrofines, en la capacitat reproductora, en el metabolisme lipidic i la sensibilitat a la insulina, i en el creixement i la maduracio esqueletica, en ambdos sexes. La sequencia codificant de la proteina esta continguda en nou exons (exons 2-10), que s'estenen aproximadament al llarg de 35 kb de DNA. Els codons d'iniciacio i terminacio de la traduccio son als exons 2 i 10, respectivament. Fins ara, s'han documentat onze casos de deficiencia completa de l'aromatasa secundaris en mutacions del gen CYP19. El patro dels nivells serics hormonals indica una baixa concentracio d'estrogens i alta d'androgens, FSH, i, ocasionalment, tambe d'LH, sempre, pero, depenent de l'edat i del sexe. Durant la infantesa, s'observa un dimorfisme sexual en el paper dels estrogens en la regulacio de la secrecio de les gonadotrofines. Aquests pacients presenten un risc elevat de desenvolupar quists d'ovari, fins i tot abans de la pubertat. Finalment, l'estudi d'aquests pacients tambe ha estat util per ill. ustrar el paper dels estrogens en el desenvolupament esqueletic, en la maduracio de les epifisis i en el brot de creixement puberal, en ambdos sexes.

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