Further Studies on Loss of Sensitivity to Anterior Pituitary-Like Hormone of Pregnancy Urine

Abstract

It is well known that both the anterior pituitary sex hormone and the anterior pituitary-like hormone of pregnancy urine (A.P.L.) lose their ovary-stimulating effect after a certain time, if given daily over a long period. Hisaw 1 has recently been able to show that this loss of sensitivity may be obtained in rabbits even by the administration of subthreshold doses of anterior pituitary sex hormone, and we 2 ,³ found that the loss of sensitivity is limited to the gonadotropic preparation with which the animals have been treated previously. Animals which became insensitive to A.P.L. remained responsive to pituitary implants and vice versa.

In an attempt to determine whether this loss of sensitivity is due to the formation of specific hormone inhibiting substances as postulated by Collip 4 or simply to an insensitivity of the ovarian tissue itself, we performed the following experiments.

Five female rats, 21 days of age at the beginning of the experiment, have been injected daily with 100 R.U. of A.P.L. subcutaneously for a period of 8 months. Then they and 7 untreated females of the same size received 100 R.U. of A.P.L. intravenously. All animals were killed 1 hour after the injection. The blood of each animal was collected separately and injected in 3 doses of approximately 1.5 cc. each on 3 consecutive days into an immature rat 21 days of age, and thus tested for its A.P.L. content. The blood of all 7 previously untreated rats led to corpus luteum formation in the immature females, while the blood of the A.P.L.-insensitive animals was ineffective with one exception. The odds against obtaining such a result by chance greatly exceed 100 to 1. From this experiment we conclude that A.P.L. disappears more rapidly from the blood of the A.P.L-insensitive rat than from the blood of the normal animal.