title: Effects of host hormonal status on binding of activated estrogen receptor to nuclei from R3230AC and 7,12-dimethylbenz[a]anthracene-induced mammary tumors.
abstract: The effects of various hormonal perturbations that alter growth of two different rat mammary tumors in vivo were investigated by study of the interactions of [3H]estradiol-charged estrogen receptors ([3H]ER) with tumor nuclei in vitro. Nuclei from the transplantable R3230AC adenocarcinoma were isolated after ovariectomy, estrogen treatment, or progesterone treatment. Saturable specific binding of [3H]ER to nuclei was assayed in this in vivo-like system. Scatchard analysis of [3H]ER-nuclear binding data indicated that these perturbations did not affect affinity, which ranged from Kd 1.0 to 2.4 nM. However, the number of [3H]ER-binding sites/nucleus was altered according to the treatment: intact rats, 94,500 +/- 4,200; ovariectomy, 70,400 +/- 3,200; ovariectomy plus estradiol, 82,100 +/- 5,800; and ovariectomy plus progesterone, 73,900 +/- 2,500. Nuclei from primary tumors induced by 7,12-dimethylbenz(a)anthracene displayed similar affinities for [3H]ER, although these tumors had fewer binding sites per nucleus. Animals bearing 7,12-dimethylbenz(a)-anthracene-induced tumors were either ovariectomized or made diabetic by administration of streptozotocin, perturbations that cause regression of the majority of tumors. The number of [3H]ER binding sites per nucleus, in tumors classified according to growth characteristics in host animals subsequent to hormonal perturbation, was: intact growing 36,300 +/- 3,400; ovex regressing, 15,400 +/- 3,400; ovex, estrogen-treated growing, 28,100 +/- 2,700; diabetic regressing, 19,500 +/- 2,400; diabetic static, 32,100 and diabetic growing, 42,000 +/- 7,100. These results indicate that (a) the number of nuclear ER-binding sites can be reduced by hormonal interventions that cause tumor regression and (b) endogenous ovarian hormones may play a role in regulating nuclear ER binding.
authors.affiliation: Department of Biochemistry, University of Rochester School of Medicine and Dentistry, New York 14642.
authors.forename: C M
authors.initials: CM
authors.lastname: Klinge
authors.forename: R A
authors.initials: RA
authors.lastname: Bambara
authors.forename: S
authors.initials: S
authors.lastname: Zain
authors.forename: R
authors.initials: R
authors.lastname: Hilf
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D010052:Ovariectomy; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D012739:Gonadal Steroid Hormones; D011960:Receptors, Estrogen; D015127:9,10-Dimethyl-1,2-benzanthracene; D011189:Potassium Chloride