The fate of an intrauterine injection of progesterone–1α, 2α–3H (P–3H) was investigated in the Hooker–Forbes bioassay system. Essentially no radioactivity from P–3H administered in one uterine horn appeared in the contralateral horn at any time, i.e., there was no detectable circulation of labeled compounds. The disappearance rate from the uterus was indicative of high affinity binding of a limited amount of steroid. After injection of P–3H, one major metabolite (NP), less polar than progesterone, but apparently not 5α– or 5β–pregnane–3, 20–dione, was found in amounts similar in concentration to that of P–3H. The addition of 1% by weight of 16α–hydroxyprogesterone (16α–OH–P) to progesterone in the injection mixture antagonized the stromal nuclear response that is the end–point of the bioassay. When the same proportion of 16α–OH–P was injected with 3H–progesterone, the concentration of labeled progesterone metabolites increased significantly, p < 0.025, by 120%, whereas the concentration of P–3H decreased insignificantly by 16%. Specifically, the metabolite, NP, was increased by 101%, and the appearance of a second metabolite, 3α–hydroxy–5α–pregnan–20–one, was detected. Thus, a small concentration of 16α–OH–P has a profound effect on the accumulation of the products of progesterone metabolism in the uterus. These products are apparently responsible for the failure of progesterone to elicit the stromal cell nuclear response.
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