Binding capacity of rat liver glucocorticoid receptor in different periods after single neonatal benzpyrene treatment (imprinting)

Newborn rats of both sexes were treated (imprinted) with 20mg of benzpyrene. Two hours, 2 days, 1, 2, 3 weeks, 1 month and 2 months after imprinting the liver glucocorticoid receptors were studied for binding of dexamethasone. Two-hour and 2-day values were not appreciable. One week after treatment the receptor's affinity was extremely low both in control and treated treated animals. Two weeks after imprinting a significant difference in density (lower) and affinity (higher) was observed between the male treated and control animals. At 3 weeks and one month the binding capacity of treated and control animals was equal however, at 2 months Bmax of males increased and that of females decreased significantly in the neonatally benzpyrene treated animals. This means that for the development of perinatal imprinting effect a long time is needed, and the effect is manifested after a period of lability

Effect of tamoxifen treatment at adolescent age on the sexual behaviour and steroid hormone receptor binding of adult female rats

Hormonal imprinting takes place perinatally, at the first encounter between the target hormone and its developing receptor. However, there is a secondary critical period of imprinting at puberty. In these periods molecules similar to the hormones (members of the same hormone family, antagonists, certain environmental pollutants, etc.) can cause faulty imprinting with lifelong consequences. In the present experiments 5+2 days of tamoxifen treatment (120mg/day) at adolescent age dramatically (from approx. 40% to 10%) reduced the sexual activity (Meyerson index and lordosis quotient) of female rats, soon after the finishment of the treatment and between four to six weeks after treatment. Similar results were observed in animals neonatally treated with allylestrenol and tamoxifen treated at puberty. Thymic glucocorticoid receptor and uterine estrogen receptor binding capacity were not influenced

The biological basis and clinical significance of hormonal imprinting, an epigenetic process

The biological phenomenon, hormonal imprinting, was named and defined by us (Biol Rev, 1980, 55, 47-63) 30 years ago, after many experimental works and observations. Later, similar phenomena were also named to epigenetic imprinting or metabolic imprinting. In the case of hormonal imprinting, the first encounter between a hormone and its developing target cell receptor—usually at the perinatal period—determines the normal receptor-hormone connection for life. However, in this period, molecules similar to the target hormone (members of the same hormone family, synthetic drugs, environmental pollutants, etc), which are also able to bind to the receptor, provoke faulty imprinting also with lifelong—receptorial, behavioral, etc.,—consequences. Faulty hormonal imprinting could also be provoked later in life in continuously dividing cells and in the brain. Faulty hormonal imprinting is a disturbance of gene methylation pattern, which is epigenenetically inherited to the further generations (transgenerational imprinting). The absence of the normal or the presence of false hormonal imprinting predispose to or manifested in different diseases (e.g., malignant tumors, metabolic syndrome) long after the time of imprinting or in the progenies

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

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