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.

On the mechanism of action of oral contraceptives. I. Effect of lynestrenol on ovum implantation and oviductal morphology in the rat.

PIP: 2 experiments on virgin female rats (average weight 200 gm) were performed to study the effects of small doses of lynestrenol on the early pregnancy of the rat. In both experiments, the rats were caged with a mate overnight and if, on the following morning, spermatozoa were found on the vaginal smear, that day became Day 1 of pregnancy. In Experiment 1, the test group (15) received .1 mg lynestrenol sc and the control group (14) 1 ml propyleneglycol on Days 2, 3, 4, and 5 of pregnancy. Experiment 2 differed in that the rats received 1 mg dosages of lynestrenol. On Day 7 of pregnancy, Experiment 1 rats were killed and their ovaries and genital tracts were examined. In Experiment 2, the rats were permitted to live until Day 23 to see if they would achieve full-term pregnancy. If delivery did not occur, they were killed (Day 25) and examined for fetuses. In Experiment 1, the dose did not significantly increase the number of lost ova (20% in controls), as indicated by the implanted embryos/recent corpora lutea ratio counted on Day 7. There was an increase in the number of ciliated cells in the epithelium and a diminution of the deciduoid tissue of the stroma. No histological changes were seen in the ovaries, embyros, or uteri. The 1 mg dosage of lynestrenol prevented pregnancy in all of the rats. Doses were smaller than those needed to inhibit ovulation, and the time of administration of the doses excluded any action on sperm transport, capacitation, or penetration. Lynestrenol would appear to act on the pregnant rat's genital tract, as oviducts displayed evidence of estrogen stimulation.^ieng