Competition by Estrogens for Catecholamine Receptor Binding In Vitro

We have examined the ability of various steroids to compete for high‐affinity binding of 3 H‐labeled ligands to catecholamine receptors in membranes prepared from rat cerebral cortex, striatum, and anterior pituitary. Ligands employed were: [ 3 H]WB4101, [ 3 H]prazosin, [ 3 H]yohimbine, and [ 3 H]clonidine (alpha‐noradrenergic); [ 3 H]dihydroalprenolol (beta‐noradrenergic); [ 3 H]spiperone and [ 3 H]ADTN (dopaminergic). Only the 17 β estrogens were effective and only binding of [ 3 H]spiperone and [ 3 H]ADTN in striatum and [ 3 H]WB4101 and [ 3 H]prazosin in cerebral cortex was reduced. Thus putative dopaminergic and alpha 1 ‐noradrenergic sites alone appear to recognize estrogens. A slight competitive effect on [ 3 H]spiperone binding to anterior pituitary membranes was also observed. Among the 17 β estrogens tested, the most effective in all cases was the catechol estrogen 2‐hydroxyestradiol (2‐OHE 2 ). The ability of 2‐OHE 2 (IC 50 = 20–30 μM ) to inhibit ligand binding to alpha 1 receptors was comparable to that of norepinephrine (IC 50 = 10–20 μM ), whereas for dopamine receptors in striatum and pituitary 2‐OHE 2 was an order of magnitude less effective than dopamine (IC 30 = 12 μM ) in reducing binding of 3 H ligands. Estradiol‐17 β and 2‐hydroxyestrone were also able to inhibit binding, but the order of steroid potency was different for alpha 1 and dopaminergic receptors. Progesterone, testosterone, and corticosterone were without effect in all cases. These results show that there is specificity of steroid interactions with catecholamine receptors in the brain, both in terms of steroid structure and receptor type. The possible relevance of these interactions to neuroendocrine function is discussed.