Summary
Aromatase or cytochrome P450 is the enzyme that synthesizes estrogens from androgens. Its gene (CYP19) is located on 15q21.1 Aromatase deficiency is a rare disease, transmitted as an autosomal recessive trait. Point mutations identified so far are mainly located in exons 9 and 10. During the pregnancy, foetal androgens are not converted into estrogens due to placental aromatase deficiency resulting in an increased level of maternal plasma testosterone and low estrogen levels. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female baby presents with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries. In man, diagnosis occurs later during the adulthood, with tall stature due to incomplete epiphyseal closure, eunuchoid proportion of the skeleton, associated with osteoporosis and obesity. Administration of low doses of estrogen leads to bone maturation after complete epiphyseal closure and to an increase in bone mineral density. In blood plasma, levels of estrogens are very low while FSH, LH and testosterone are slightly increased. Two patients (of 5) present with cryporchidism uni or bilateral. Spermogram shows an oligo-asthenospermia. Sexual activity is normal. The most intriguing feature is the existence of a marked metabolism phenotype : steatohepatitis, insulino-resistance with acanthosis nigrans and elevated triglycerides concentration. CYP 19 is ubiquitary expressed mainly in the gonads, placenta, adipose tissues, osteoblasts, breast, and brain... It is comprised of 10 exons, the first of which is transcribed but not translated. There are several alternative exons 1 with a tissue-specific expression, each of which is associated with a distinct promoter. Corresponding mRNAs differ by their 5' termini but produce a single identical protein. *Author: Dr ML Kottler (November 2004)*.
