PHENOTYPIC FEMINIZATION IN A GENETIC MALE DOG CAUSED BY NONFUNCTIONALANDROGEN RECEPTORS

A dog raised as a female pup did not have utero-ovarian structures whe n ovariohysterectomy was attempted at 6 mo of age. Three months later, the dog exhibited male-like behavior, and 2 symmetrical testicular-sh aped structures arose bilateral to the vulva. Intersex cases such as t his one may involve chromosomal abnormalities, defects in testicular s ecretions or androgen insensitivity in tissues of the sex accessories. Serum concentrations of testosterone and dihydrotestosterone were mea sured in the intersex and in intact normal male (control; n=7) dogs. I n addition, 5 alpha-reductase enzyme activity was determined in the go nadal tissue of the intersex dog and control dogs. Androgen receptors were studied in cultured fibroblasts from the genital skin of the inte rsex and control dogs. The cytogenetic studies identified the animals karyotype to be 78 XY. All complete cells from the gonadal tissue show ed an XY sex chromosome complement. Serum testosterone concentrations before and after challenge with hCG were not different between the int ersex and control dogs (6.2 vs 5.72 +/- 1.8 ng/ml and 9.5 vs 8.69 +/- 2.39 ng/ml before and after hCG challenge, respectively). Similarly se rum dihydrotestosterone concentrations were not different between the intersex and control dogs before and after challenge with hCG (158 vs 162 +/- 1.4 pg/ml and 270 vs 278.71 +/- 45.98 pg/ml before and after h CG challenge, respectively). The 5 alpha-reductase enzyme activity of the gonads was not different between the intersex and control dogs (10 5 pmol/h/mg protein vs 110 +/- 2.4 pmol/h/mg protein). The Bmax values of binding in the control dogs fibroblast strains were 25 +/- 3.5 fmo l/mg protein. However, specific binding of dihydrotestosterone was vir tually undetectable in the fibroblasts cultured from the intersex dog. These results exclude chromosomal abnormalities and deficient secreti on of testosterone and dihydrotestosterone as causative factors. Becau se fibroblasts cultured from genital skin lacked any ability to specif ically bind dihydrotestosterone, it is suggested that nonfunctional an drogen receptors in some tissues of the sex accessories contributed to the feminine phenotype of this particular dog.