Molecules acting on receptor level at weaning, durably influence liver glucocorticoid receptors

Abstract

In the experiments the effect of late hormonal imprinting to the liver glucocorticoid receptors were studied. Three-week-old (weanling) female rats were treated with five molecules acting at receptor level and four weeks later receptor kinetic analysis was done on liver glucocorticoid receptors. The tricyclic antidepressant, histamine and serotonin receptor blocker mianserin positively influenced receptor density and negatively receptor affinity. Vitamin D3 and the environmental pollutant benzpyrene elevated receptor density. Mifepristone (RU 486) which is bound by progesterone- and glucorticoid-receptor without postreceptorial effects was ineffective as well, as the H1 receptor blocker chlorpheniramine. The results demonstrate that receptor-level-acting foreign molecules can durably influence the binding capacity of glucocorticoid receptors, however, this is not a general phenomenon and it is not dependent on the type of receptors (membrane or cytosol). Those molecules were effective which 1. have receptor in the same receptor family (vitamin D3) and have postreceptorial effect, or 2. have a structure similar to steroids (benzpyrene) or 3. deeply influenced steroid receptors in earlier experiments (mianserin). This effect should be considered before administering such type of medicaments.