We have found that mouse ear oedema induced by the topical application of arachidonic acid is not a specific screen for compounds inhibiting the lipoxygenase or cyclo-oxygenase pathways of arachidonic acid metabolism. Although such compounds are able to reduce the oedema substantially, pharmacological agents such as histamine antagonists, phosphodiesterase inhibitors, free radical scavengers, and also various compounds not normally considered to have anti-inflammatory properties, can equally effectively reduce the oedema. A mutual potentiation of the effects of prostaglandins, leukotrienes and mast cell-derived histamine would allow many, but not all, of the active agents to be rationalised. The ability of compounds not influencing these three types of inflammatory mediators to reduce the oedematous response means the model is of limited value for directed screening.

The synthesis of a series of 7-aroyl-2,3-dihydrobenzo[b]furan-3-carboxylic acids and 7-benzoyl-2,3-dihydrobenzo[b]thiophene-3-carboxylic acids is described. The isomeric 4-benzoyl-1,3-dihydrobenzo[c]furan-1-carboxylic acid was also prepared. Compounds were evaluated for analgesic activity in the mouse phenyl-p-quinone-induced writhing test. Selected compounds were tested for their ability to produce gastric damage in fasted mice and for inhibition of prostaglandin synthetase activity in vitro. Zomepirac was used as a reference. Structure-activity relationships are discussed. One of the compounds, 7-benzoyl-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (2c), combined potent analgesic activity with low gastric irritancy.

SUMMARY A search has been conducted for specific, 5α-dihydrotestosterone-binding proteins in a wide variety of tissues and cells upon which androgenic steroids have pronounced morphological and biochemical effects. High affinity binding proteins of this nature have been identified in cytoplasmic and nuclear extracts from a diversity of accessory sexual glands of many species, mouse kidney, testis and certain experimental androgen-dependent tumours. They are notably absent in most types of skeletal muscle and in soluble extracts prepared from prokaryotic organisms. The implications of these findings to the mechanism of action of androgenic steroids are discussed. While the selective binding of 5α-dihydrotestosterone indubitably plays a role of paramount importance in the mechanism of action of androgens in many accessory sexual glands throughout life, this process may be of importance in other tissues only during the period of early growth and development. A severe limitation to the importance of the binding of 5α-dihydrotestosterone in certain adult tissues is imposed by the very low activity of the enzyme, 5α-reductase, responsible for the formation of 5α-dihydrotestosterone.

1. Implantation of diethylstilboestrol pellets into adult male rats brings about similar biochemical changes in the nucleic acid and protein metabolism to castration. 2. The avidity of the prostate for labelled diethylstilboestrol was greater than that of the other organs examined. 3. Uptake of labelled diethylstilboestrol and testosterone into the nuclei of the rat prostate is greater in castrated rats than in controls. 4. Diethylstilboestrol appeared to be associated with the protein and not with the DNA fraction of the nucleus.

No abstract