Estrogen secreting adrenal adenocarcinoma in an 18-month-old boy: Aromatase activity, protein expression, mRNA and utilization of gonadal type promoter

We examined clinical, endocrinological and molecular biological aspects of an estrogen-secreting adrenal carcinoma in an 18-month-old male to clarify the pathogenesis of this condition. An 18-month-old boy was referred for ev aluation of progressive bilateral gynecomastia and appearance of pubic hair . The patient had elevated plasma estradiol (349 pg/ml) and testosterone (2 60 ng/dl) levels that completely suppressed FSH and LH levels, and was subs equently diagnosed with an adrenal tumor on the right side. After removal o f a 300-g adenocarcinoma, gynecomastia regressed and essentially normal hor mone levels were restored. determined by the H-3-water method was 71.0-104. 4 pmol/min/mg protein. High levels of aromatase protein and mRNA in the tum or tissue were also demonstrated, while neither aromatase activity nor prot ein was detected in normal adrenal glands. To investigate the regulation of aromatase expression in the adrenal carcinoma, we examined the usage of al ternate promoters responsible for aromatase gene transcription. In the pres ent case, the amounts of aromatase mRNA utilizing gonadal types of exon Ic (1.3) and Id (II) were significantly higher than those that using other exo n Is. This result suggested that the utilization of a gonadal-type exon 1 m ight be involved in the overproduction of aromatase in estrogen-secreting a drenal carcinoma.