Regulation by steroid hormones of phosphorylation of specific protein common to several target organs

Abstract

The effect of in vivo administration of steroid hormones on the endogenous phosphorylation of individual proteins in cell sap from several target tissues has been studied using the technique of discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The hormones studied (and their respective target organs) were: 17 beta-estradiol [1,3,5(10)-estratriene-3, 17beta-diol] (uterus); testosterone (17 beta-hydroxy-4-androsten-3-one) (ventral prostate and seminal vesicle)' cortisol (11beta, 17alpha, 21-trihydroxy-4-pregnene-3,20-dione) (liver); aldosterone (the 18.11-hemiacetal of 11beta,21-dihydroxy-3,20-dioxo-4-pregnen-18-al) (toad bladder). In each of the five target organs studied, pretreatment with the appropriate hormone reduced the amount of 32P incorporated from [gamma-32P]ATP into an apparently common protein band present in the cytosol fraction. The endogenous phosphorylation and dephosphorylation of this protein was also regulated by cAMP. This protein, designated SCARP (steroid and cyclic adenosine 3':5' monophosphate regulated phosphoprotein), was estimated to have an apparent molecular phoprotein), was estimated to have an apparent molecular weight of 54,000 in the gel electrophoresis system used. The effect of the steroid hormones in decreasing the phosphorylation of SCARP was specific for their respective target tissues. The effect of 17beta-estradiol and of testosterone on SCARP could be observed as early as two hours after a single dose of the steroid. A protein synthesis inhibitor, cycloheximide, abolished the effect of the steroid hormones, but not that of cAMP, on the endogenous phosphorylation of SCARP. The results suggest that steroid hormones regulate either the amount of SCARP or its ability to become phosphorylated. This regulation of a single species of protein by several types of steroid hormones in different target organs raises the possibility that this common biochemical action may be a component of the mechanism by which these steroids achieve some of their biological effects.