This research project proposes the characterization of corticoid binding sites in the spinal cord of the rat, to study their occupancy by endogenous adrenal hormones, and to search for biological markers of corticoid action in this tissue. In spite of the numerous reports covering corticoid action in brain centers, there is paucity of information regarding the spinal cord, both in terms of receptor identification and biochemical mechanism of hormone action.
Specific aims of the project are: (1) To selectively labeling glucocorticoid sites in the spinal cord with ligands such as dexamethasone or corticosterone in the presence of pure non-radioactive mineralocorticoids (RU 26752 and RU28318) to block mineralocorticoid sites, and to specifically label mineralocorticoid sites with aldosterone in the presence of a glucocorticoid receptor blocker (RU 26988). Properties of binding sites will then be studied, such as regional distribution, equilibrium parameters, sedimentation coefficients, relative binding affinities, etc. (2) Distribution of binding sites will be next compared in areas of the cord which concentrate endogenous or exogenous adrenal hormone, after experimental manipulations leading to increases or decreases in adrenocortical function. For this purpose, the cord will be dissected into the following regions: C1-C3, C4-C8, T1-T8, T9-L3, L4-L8 and horse tail plus filum terminale. Binding sites and adrenal hormone will be localized in white or grey matters by means of the punch technique, and employing receptor assay or radioimmunoassay respectively. (3) Lastly, to support a role for corticoid binding sites in spinal cord function, we will perform determination of enzymes (glycerol-3-phosphate dehydrogenase, tyrosine hydroxylase, ornithine decarboxylase), nucleotides (cAMP) and neurotransmitters (serotonin, norepinephrine), which are regulated by adrenal hormones in other parts of the nervous system. Information on the effect of corticoid hormones on these markers in the spinal cord is partial or incomplete. It is our belief that this proposal can fill a gap presently existing in the knowledge of steroid-receptor interaction in the nervous tissue, and will be important for the better understanding of the effects of corticoid therapy in spinal cord injury and degenerative illness.
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