Further evidence for histamine facilitating oestrogen action in the uterus

The effect of doses of estradiol ranging from 0-0125 to 1-6 mug on the uterine weight of the spayed rat was studied 24 h after a single s.c. injection of the hormone. The lowest dose inducing a significant increase in uterine weight was 0-32 mug. When histamine dihydrochloride (50 mg) was simultaneously injected with the hormone, the effect of small doses of oestradiol (0-0125--0-2 mug) was significantly increased. When oestradiol and histamine were administered for 3 successive days, the uterine weight of animals receiving 0-0125 mug oestradiol, if compared with untreated controls, was increased only in the histamine-treated group. When 0-05 mug oestradiol was administered histamine did not modify the increase already produced by the hormone. Spermidine and burimamide, two substances structurally related to histamine, increased [3H]oestradiol uptake by the spayed rat uterus. The latter (an antihistamine drug acting on H2-receptors) as well as pyrathiazine (a histamine releaser having antihistamine properties) decreased the effect of histamine on oestradiol uptake whereas diphenhydramine (an antihistamine drug blocking H1-receptors) did not modify it. Pyrathiazine was itself able to diminish oestradiol uptake.