The Effect of Catecholestrogens on the Growth of Prolactin-Secreting Pituitary Tumors and Normal Prolactin Synthesis in the Rat*

Abstract
The effects of the catecholestrogens 2-hydroxyestrone (2-OHE1) and 2-hydroxyestradiol (2-OHE2) on the growth of the estrogen-induced transplantable PRL-secreting rat pituitary tumor 7315a were compared with the effects produced by the chronic administration of estradiol (E2) and estriol (E3). 2-OHE2 (100 μg/kg·day for 27 days) inhibited pituitary tumor growth by 38 ±8% (P < 0.05), while producing no change in the weight and total PRL content of the pituitary gland. It exerted a small uterotropic effect in tumor-bearing rats and impaired body growth slightly. 2-OHE1 (100 μg/kg·day) inhibited pituitary tumor growth by 56 ± 9% (P < 0.01) and suppressed both the weight (P < 0.01) and the total PRL content of the pituitary gland (P < 0.01). The compound normalized the weight of the uterus and did not influence body growth. Both E2 (20 μg/kg·day) and E3 (100 μg/kg·day) profoundly inhibited pituitary tumor growth (−98 ± 3 and −83 ± 6%, respectively; P < 0.01 and P < 0.01, respectively). These steroids had a strong positive effect on the pituitary PRL content and the pituitary, ovarian and uterine weights, while they significantly suppressed body growth. The effect of 2-OHE2 on synthesis and release of PRL by the normal pituitary gland was studied. 2-OHE2 (20 μg/day for 6 days) exerted a positive effect on PRL synthesis and release by male rats, which was additive to that of E2. In normal female rats, however, no effect of 2-OHE2 administration (25 μg/day for 4 days) was noticed, while it counteracted the positive effect of E2 completely. 2-OHE1 and 2-OHE2 inhibit pituitary tumor growth via a mechanism which is different from that of high concentrations of E2 and E3. 2-OHE1 exerted a strong antiestrogenic action on tumor growth and normal PRL synthesis, while the effects of 2- OHE2 on normal PRL synthesis and release seem to be estrogenic or antiestrogenic, depending on the estrogen status of the animal.