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Structural Alterations and Stabilization of Rabbit Uterine Estrogen Receptors by Natural Polyamines¹

Division of Medical Oncology, Department of Medicine, University of Minnesota Hospital and Masonic Cancer Center, Minneapolis, Minnesota 55455

Estrogenic regulation of gene expression involves interaction of the hormone with its receptors, which undergo structural and conformational changes to interact with specific DNA sequences. Putrescine, spermidine, and spermine, are ubiquitous cellular components. We studied the effects of these polyamines on rabbit uterine estrogen receptors by sucrose gradient centrifugation and ligand dissociation kinetics. The native 7S receptor converted to a 9S–10S form in the presence of 100 µM spermidine or spermine. Higher concentrations caused precipitation of the receptor. This precipitation was reduced by RNase treatment of the receptor. RNase-treated receptors sedimented at 4S and 7S regions of sucrose gradient. The dissociation rate constant (k) of the 4S receptor is 2.8 x 10^-3 min^-1 in the presence of 1 mM spermidine, compared to a control value of 7.7 x 10^-3 min^-1. Similar effects were observed with putrescine and spermine. The dissociation of the RNase-treated 7S receptor was biphasic, with about 50% of the receptors dissociating at a faster rate (k₁ = 40 x 10^-3 min^-1) than the other half (k₂ = 7.4 x 10^-3 min^-1). Spermidine (1 mM) caused a 2-fold reduction in k₂, whereas k₁ was not affected. This study shows that polyamines affect the structural organization and ligand dissociation kinetics of estrogen-receptor complexes.

¹ This study was supported in part by a New Investigator Research Award from the NIH (CA-42439-01 to T. T.) and by grants from the American Cancer Society (IN-13-X-33 to T. T.) and the Minnesota Medical Foundation (D. T. K.).

² To whom requests for reprints should be addressed, at University of Minnesota, Section of Medical Oncology, Box 168 UMHC, Mayo Memorial Building, 420 Delaware Street, SE, Minneapolis, MN 55455.

Received 8/ 4/86. Revised 12/ 2/86. Accepted 1/ 2/87.