DISTRIBUTION PATTERN OF A NON-STEROID COMPOUND WITH ENDOCRINE ACTIONS, 14C-BIS(P-HYDROXYPHENYL)CYCLOHEXYLIDENEMETHANE (COMPOUND F6060) AND ITS DIACETATE (COMPOUND F6066)

Abstract

ABSTRACT While testing a series of unsymmetrical diphenylalkenes, it was observed that bis(p-hydroxyphenyl)cyclohexylidenemethane (compound F6060) and its diacetate (compound F6066) had an oestrogenic activity of about 1/1000 that of oestradiol benzoate. Further pharmacological investigations showed antioestrogenic (chicken oviduct test) and antigestagenic (Clauberg test) properties. The compounds had a low toxicity both in acute and chronic tests. In order to further elucidate the physiology of the compounds they were labelled with 14C and their distribution in the body was investigated by whole body autoradiography in male and female (pregnant and nonpregnant) mice. A rapid and selective accumulation of both compounds was observed in the corpora lutea. A selective and progressively increasing accumulation was also seen in the visceral yolk sac epithelium. A slight accumulation was also found in the hypophysis, the adrenal cortex, the endometrium, the interstitial tissue of the testis and ovary, the epididymis and the mucosa of the seminal vesicles. No accumulation was found in the prostate. There was a very low concentration in the foetus during the whole course of observation. In addition to the radioactivity in the liver, bile and intestinal lumen, the only organs showing any retention 24 hours after administration were the corpora lutea and yolk sac epithelium. The distribution pattern is in agreement with the physiological findings of an antigestagenic effect. The concentration in the yolk sac epithelium suggests further studies on the localization of the different steps in gestagen biosynthesis.