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Interaction of contraceptive progestins and related compounds with the oestrogen receptor. Part I: Effect on (3H)oestradiol distribution pattern in the ovariectomized rat.

The distribution pattern of oestradiol in ovariectomized rats as a function of time has been studied following intravenous adminstration of the tritiated hormone. Oestrogen specific binding with limited capacity was observed in the uterus, vagina, anterior pituitary, adrenals, preoptic area, hypothalamus, amygdala, septum and tractus diagonalis. Maximal uptake of oestradiol in the pituitary occurred within 5 min, in the uterus 60 min after injection, and remained almost unchanged at this level for more than two hours. The binding capacity per mg tissue decreased in the order pituitary, uterus, vagina, preoptic area, adrenals, hypothalamus, amygdala, spetum and tractus diagonalis. The hormone concentration in these tissues one hour after (3H)oestradiol injection was lowered by previous administration of ethinodiol, norethinodrel, lynestrenol and norethindrone, whereas medroxyprogesterone, chlormadinone, megestrol and methyllynestrenol had no effect. The same results were obtained, when instead of the steroid alcohols the corresponding acetate esters were administered. For norgestrel, oestrenol and nortestosterone the effect in the dose range studied was limited to the pituitary and preoptic area. For lynestrenol the inhibition of oestradiol binding in the target tissues was almost the same when the progestin was given 60 and 5 min before oestradiol, whereas in the case of administration 30 min after oestradiol no inhibition was observed. The reduction of oestrogen binding appeared to be dose-dependent, but the dose required to obtain a certain effect for the uterus was four times as high as for the pituitary. Discrepancies between previous studies and the implications of the present findings for the mechanism of action of ovulation inhibition by these progestins are discussed.