Effect of neonatal treatment with mifepristone or tamoxifen on the binding capacity of the thymic glucocorticoid or uterine estrogen receptor of adult rats: data on the mechanism of hormonal imprinting.
For studying the mechanism of perinatal hormonal imprinting newborn rats were treated with a single injection of the antihormones, mifepristone (RU486) or tamoxifen (100 microg each). Glucocorticoid receptors of thymi of 6 weeks old male and female, and uterine estrogen receptors of 2 months old female rats were studied for dexamethasone or estradiol binding, respectively. Tamoxifen caused faulty imprinting both in the thymic and uterine receptors, increasing affinity and density of males, and decreasing females' glucocorticoid receptors as well, as decreasing the density of uterine estradiol receptors. Neonatal mifepristone treatment was indifferent to the thymus, and decreasing to density of uterine estrogen receptors. Males' body weight significantly decreased 6 weeks after tamoxifen treatment. The results suggest that imprinting can not be provoked by a molecule (hormone antagonist) which can bind to the receptor without any postreceptorial events (mifepristone/glucocorticoid receptor), in the presence of some postreceptorial effects the reaction takes place, however the strongest reaction can be observed by the hormone analogue (tamoxifen) with postreceptorial (agonist) effect, not considering that the receptor is the direct target of the molecule or a cross-reaction is present.
Csaba
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Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary. csagyor@net.sote.hu
Inczefi-Gonda
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D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D018392:Genomic Imprinting / Q000187:drug effects; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D006727:Hormone Antagonists; D011960:Receptors, Estrogen; D011965:Receptors, Glucocorticoid; D013629:Tamoxifen; D015735:Mifepristone; D004958:Estradiol; D003907:Dexamethasone