Androgen Insensitivity in Male Pseudohermaphrodite Rats1

Determinations were made of the citrate and nitrogen content of urine from male pseudohermaphrodite rats before and after injection with testosterone propionate. Controls were normal male and female siblings of pseudohermaphrodite males, and normal maternal carriers for the mutant gene for male pseudohermaphroditism. Testosterone caused an increase in weight of all normal animals, male and female, whereas that of male pseudohermaphrodites remained relatively stable. The citrate and nitrogen content decreased in the urine of all normal animals while testosterone was administered, but they did not undergo a significant change in that of male pseudohermaphrodites subjected to the same treatment. Since testosterone has a protein anabolic effect and the citrate and nitrogen titer in urine reflects the rate of metabolism, the preceding results indicate that many tissues of male pseudohermaphrodite rats are insensitive to androgen, whereas those in normal rats are not. (Endocrinology 89: 615, 1971) I THE RAT and many other species, the administration of testosterone increases the rate of protein anaboKsm. In animals so treated, the rate of excretion of urinary nitrogen and citric acid decreases (1). Following large doses of testosterone, patients with the complete form of testicular feminization fail to exhibit changes in their urinary nitrogen, phosphorus and citric acid (2). Male pseudohermaphrodite rats are genetic males which exhibit a female phenotype. Affected animals lack wolffian and mullerian derivatives except for a blind vagina which varies from a dimple to about 2 mm in depth. They exhibit a pair of inguinal testes. The mutation is passed by the mother to one half of her male offspring. They are produced in relatively large numbers from a King-Holtzman strain in the Stanley-Gumbreck colony at the Received October 6, 1970. Supported by NIH Grants HD 01921-02 and HD 03909-02. 1 Presented in part at the 82nd Annual Session of the American Association of Anatomists and the 52nd Meeting of The Endocrine Society. 2 Present address: Department of Anatomy, University of Tennessee College of Medicine, Memphis, Tenn. 38103. University of Oklahoma Medical Center. In many respects, the conditions manifested in the male pseudohermaphrodite rat resemble those seen in testicular feminization in man (3, 4). Insensitivity to androgen appears to be a phenomenon shared by both (5, 6). The present work was undertaken in order to show the result of measuring citric acid and nitrogen in urine of male pseudohermaphrodite rats before and after the administration of testosterone propionate. Materials and Methods Two groups of rats were used. There were 20 animals in group 1 and 15 in group 2. Both groups included 4 types of animals. The types and number of each type in each group are indicated in Table 1. All rats belonged to the King-Holtzman strain from the Stanley-Gumbreck colony. Each rat in group 1 was given a sc injection of 0.25 ml of sesame oil daily for 22 days. On the eleventh day, 4 mg of testosterone propionate was added to each daily dose of sesame oil. During the first and last 10 days of this entire regimen, the urine from these animals was analyzed for citric acid content. Group 2 contained 3 subgroups according to the number of days the members therein were treated. Those in subgroup 1 received subcutaneous injecTABLE 1. Number and type of animals used Male pseudohermaphrodites Normal males Normal females Mothers of pseudohermaphrodites Group 1 (citrate) Group 2 (nitrogen)