Incomplete testicular feminization syndrome: studies on androgen receptor(AR) function, AR gene analysis, and aromatase activities at puberty and long-term observations of clinical and hormonal features from infancy to puberty.

A female infant with partial androgen insensitivity (PAIS) was first seen at 4 months of age with slight virilization of the genitalia and externally palpable testes. Sex chromosome was 46,XY. She received left orchidectomy and exploratory laparotomy at 2 yr of age. At exploratory laparotomy, neither a uterus nor fallopian tubes were found. The right testis was preserved by fixing it at the external inguinal ring expecting spontaneous pubertal maturation. After discharge, serum levels of LH, FSH, testosterone (T) and estradiol (E2) were measured annually, and the steroid responses to hCG stimulation were examined every two yr. At the age of 10 yr, she developed breasts and a very feminine body habitus. At 12 yr, she received a clitoroplasty and right orchidectomy. The fibroblast cultures were made from the genital skin whereby androgen receptor (AR) binding was assessed by radioreceptor assay using 3H-DHT as the ligand, and thermoinstability of AR was noted despite normal maximum binding (Bmax) and dissociation constant (Kd) at 22 degrees C. But another binding experiment with 3H-Mibolerone resulted in the lack of receptor binding. AR gene analysis with direct sequencing of coding exons of the gene revealed no abnormality of the AR gene. 5 alpha-reductase activity was normal. Aromatase activity appeared to be enhanced in the genital skin fibroblast (GSF) cells as well as in the testicular tissue. The results of these studies indicated that the patient had PAIS with impaired AR functions and increased aromatase activity. After the discharge, the patient has maintained feminine phenotype, receiving estrogen therapy with mestranol 0.02 mg/day po.