Ionic transport through model membranes. II. Function of cholesterol and steroid hormones

Abstract

1. 1. The kinetics of transfer of a water-soluble azo dye, Orange IV, from an aqueous into phospholipid micelles in an adjacent organic phase have been investigated as a method of evaluating the possible effects of various hydrocarbons on the structure of the lipid micelles and interfacial films. The transport of this dyestuff probe apparently requires the presence of unsaturated alkyl chains in the lipid, provided by egg phosphatidylcholine or by synthetic lecithin (1-oleyl-2-hexadecyl ether). 2. 2. The kinetics had previously been shown to be retarded by those n- alkanes that are promoters of carcinogenesis. On the basis of this correlation it had been predicted n- C 18H 38 and n- C 20H 42 should be the most active biologically of the n- alkanes . This has been confirmed in detail by biological tests for promoting activity. 3. 3. Inclusion of cholesterol and various steroid metabolites, including androgens and progestogens, had profound effects on the rate of dye transport by egg phosphatidylcholine (very little transfer to the bulk organic phase was achieved by the steroids without the phospholipid). Cholesterol had the maximum retarding effect, but increased somewhat the ultimate equilibrium transfer of dye to the micelles in the organic phase. 4. 4. The C 19 steroids, dihydrotestosterone, testosterone, androsterone, and epiandrosterone enhanced the rate of transport by lecithin-cholesterol micelles in different critical ranges of concentration. The four steroids were thus ranked in the same order of effective concentration in the model transport system as they are in assays of their biological activities as androgens. The metabolic intermediate, pregnenolone, affected the transport kinetics similarly to testosterone. In contrast, the C 21 hormone, progesterone, and the estrogen analog, diethylstilbestrol, retarded ionic transport in this model.