The action of chlormadinone acetate (CAP) on the uptake of [6,7-3H]-17β-oestradiol in the castrated rat was studied. It was shown that when CAP is injected, the uptake of 3H-oestradiol diminishes significantly in the uterus and in the anterior pituitary (P < 0.01), whereas the uptake is not modified in the hypothalamus, posterior pituitary, skeletal muscle and plasma. A significantly (P < 0.01) smaller dose of CAP was required to inhibit the uptake of 17β-oestradiol by the anterior pituitary (27.2 ng) than by the uterus (1000 ng). Inhibition of oestradiol uptake can be demonstrated when CAP is administered before the oestrogen as well as when it is given subsequent to it (P < 0.01). This suggests the existence of a competitive mechanism between 17β-oestradiol and CAP for specific oestradiol receptors. When the action of CAP on different fractions of the uterine cell was studied, it was observed that the inhibition of oestradiol uptake occurs exclusively in the nuclear fraction (P < 0.01). Competition with oestrogens for specific protein receptors might be the common mechanism of action of the different manifestations of the effects of CAP.

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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.