Abstract
The effects of pharmacological doses of estradiol on the growth of the rat pituitary transplantable tumor MtF4, originally induced by chronic treatment with estrogens, have been characterized. After s.c. injection into control rats of a cell suspension prepared from the tumor, in 12 experiments, the average range of days when a new tumor became palpable was between 14.7 ± 2.3 (S.D.) and 24.5 ± 3.3. There was no significant difference between male and female rats. Daily i.m. injections of 10 µg 17β-estradiol benzoate (8 experiments) or 17β-estradiol implanted in Silastic tubing (4 experiments) partially inhibited the tumor growth, both in male and female rats, as judged by the weight and the time of appearance of the tumor. The same treatments increased the pituitary weight. Both effects were dose dependent above 3 µg 17β-estradiol benzoate per day and displayed some specificity. 17α-Estradiol (10 µg/day, i.m. or implanted in Silastic capsules) did not modify the pituitary or the tumor growth siginficantly; 17β-hydroxy-3-keto-5α-androstane (50 µg/day, i.m.) also did not modify the tumor growth. The inhibitory effect of 17β-estradiol on tumor growth has also been observed in hypophysectomized rats.
The tumor cytosol contained 30 to 220 fmol of specific estrogen-binding sites per mg protein which were characterized by: a high affinity (Kd, 0.25 to 0.65 × 10-9 m); a sedimentation constant of 6 to 8S; and their hormone specificity. A 50% competition was observed with 5 nm 17β-estradiol, 20 nm 17α-estradiol, and 50 nm estriol, while less than 10% inhibition was shown with 17β-hydroxy-3-keto-5α-androstane corticosterone, cortisol, and progesterone up to 5 × 10-6 m. Thus, 17α-estradiol, which was inactive in vivo, had an affinity only 4-fold lower than 17β-estradiol.
We conclude that pharmacological doses of 17β-estradiol inhibit in a dose-dependent manner and with some specificity the growth of the MtF4 transplantable pituitary tumor while increasing the growth of pituitary. We suggest this inhibition requires estrogen receptors and is not mediated via the pituitary, but we cannot specify whether this inhibition was direct or not.
This work was supported by the Unités d'Enseignement et de Recherche de Biologie Humaine et de Lyon-Nord.