BINDING CHARACTERISTICS OF A MAJOR PROTEIN IN RAT VENTRAL PROSTATE CYTOSOL THAT INTERACTS WITH ESTRAMUSTINE, A NITROGEN-MUSTARD DERIVATIVE OF 17 BETA-ESTRADIOL

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 39  (12) , 5155-5164
Abstract
The tissue distribution of [3H]estramustine, the dephosphorylated metabolite of estramustine phosphate (Estracyt) [an antineoplastic drug], in the male rat was compared to that of [3H]estradiol 30 min and 2 h following i.p. administration. In contrast to estradiol, estramustine was efficiently concentrated in the ventral prostate gland by a soluble protein. The binding characteristics of this protein were studied in vitro using cytosol preparations of the gland. With a dextran-coated charcoal technique, the protein bound estramustine with a broad pH optimum between pH 7 and pH 8.5, with an apparent Kd of 10-30 nM, and with a binding capacity of about 5 nmol/mg cytosol protein. The estramustine/protein complex was not retained by DNA-cellulose. None of the natural steroids tested inhibited the binding of 10 nM [3H]estramustine by more than 35% (progesterone), even when added in 4500-fold excess. The presence of a nitrogen mustard moiety at position 3 of the steroid was necessary for high-affinity binding to the protein. The protein constituted about 20% of the total cytosol protein content.