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  • Title: Binding of estrogen and antiestrogen in uterine cell nuclei: in vivo autoradiographic studies.
    Author: Ennis BW, Stumpf WE.
    Journal: J Steroid Biochem; 1988 Oct; 31(4A):405-9. PubMed ID: 3172774.
    Abstract:
    The in vivo binding of antiestrogen in nuclei within the uterine stromal, epithelial and myometrial tissue compartments was compared to that of estrogen 2-48 h after injection. Tissue binding and retention of radioactivity was also studied. Immature rats were injected s.c. with 0.36 microgram [3H]hydroxytamoxifen [( 3H]TAM(OH] or 0.24 microgram [3H]estradiol [( 3H]E2) in oil. At 2, 4, 8, 12, 24 and 48 h after injection, uteri were processed for thaw-mount autoradiography and, along with other tissues, for liquid scintillation counting. After [3H]TAM(OH) injection total radioactivity in uterus, cervix, vagina and liver reached peak levels by 8 h then decreased slowly so that by 48 h radioactivity still remained in the tissues. At all time intervals, the levels of radioactivity in heart and muscle remained low. After [3H]E2 injection radioactivity in uterus, cervix and vagina reached peak levels between 2 and 4 h then decreased rapidly so that by 12 h radioactivity was low and essentially the same as in liver, heart and muscle. These results were paralleled by the time course of nuclear binding of [3H]TAM(OH) and [3H]E2 in the uterine cell types: peak levels occurred at 8 h and 4 h, respectively. Nuclear binding was still present 48 h after [3H]TAM(OH) injection but was absent by 24 h after [3H]E2 injection. Different uterine cell types bound different amounts of both the drug and the hormone. After [3H]TAM(OH) injection the decreasing order of labeling intensity in the tissue compartments was stroma, myometrium, epithelium; in contrast, that after [3H]E2 injection was stroma, epithelium, myometrium. The results indicate that the dissimilar nuclear binding kinetics of estrogen and antiestrogen are influenced by the pharmacokinetics but the uterine cell types may also influence binding kinetics.
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