Influence of the molecular structure of steroids on their ability to interrupt gap junctional communication.
17 beta-estradiol propionate was found to reduce the gap junctional communication in a concentration range similar to that of testosterone propionate, in primary cultures of rat Sertoli cells and cardiac myocytes. Uncoupling was reversible on washing out and occurred without concomitant rise in the intracellular calcium concentration. Esterification was prerequisite for the activity of extracellularly applied steroid compounds (for example, testosterone was ineffective even at external concentrations up to 100 microM, whereas its intracellular application at 1 microM totally interrupted intercellular communication), but their uncoupling efficiency did not depend on the nature of the ester chain nor on its position on the steroid nucleus. The derivatives of two other androgen hormones (derivatives of the androstane nucleus) were also efficient as junctional uncouplers. Among five steroid molecules belonging to the pregnane family, only one (pregnanediol diacetate) interrupted the junctional communication. Neither cholic acid nor cholesteryl acetate or ouabain showed this effect. Altogether, no correlation with the presence or position of double bonds nor with the trans- or cis-fusion of the A and B rings could be recognized. These results suggest that this reversible, nondeleterious uncoupling effect of steroids is independent of the shape of the molecules and is more probably related to their size and liposolubility, that condition their insertion into the lipid bilayer. Their incorporation into the membrane could disturb the activity of the membrane proteins by a physical mechanism.
Hervé
J C
JC
Laboratoires de Physiologie Cellulaire et de Physiologie Animale, Unité de Recherche Associée au CNRS, Poitiers, France.
Pluciennik
F
F
Verrecchia
F
F
Bastide
B
B
Delage
B
B
Joffre
M
M
Délèze
J
J
D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D004951:Esterification; D004958:Estradiol / Q000031:analogs & derivatives; D017629:Gap Junctions / Q000187:drug effects*; D013256:Steroids / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D013256:Steroids; D004958:Estradiol; D002118:Calcium