Further Evidence of Adrenergic Control of Translocation and Intracellular Levels of Estrogen Receptors in Rat Pineal Gland*

Abstract

Pineal cytosol estrogen receptor sites and nuclear receptor-estradiol complexes were measured in female rats treated with estradiol. Cytosol receptors and nuclear receptorhormone complexes were inversely correlated during the estrous cycle; minimal values of the former and maximal of the latter were found in rats killed at proestrus. Estradiol (2 μg, sc) induced depletion of cytosol receptor sites and accumulation of nuclear receptor-estradiol complexes that were maximal 3–6 h after injection. Replenishment of cytosol receptors occurred 18 h after estradiol injection. One week after superior cervical ganglionectomy, cytosol and nuclear receptor levels were depressed, and significant impairment of estradiol-induced receptor depletion was found. Treatment of ganglionectomized rats with the β- adrenoceptor agonist isoproterenol, although increasing cytoplasmic receptor levels, inhibited their translocation to the nuclei. Injection of the β-adrenoceptor blocker propranolol to normal rats partially impaired the translocation of receptor-estrogen complexes brought about by estradiol. To examine the changes in receptors during the process of degeneration of sympathetic nerves that follows ganglionectomy, rats subjected to surgery 4–72 h earlier were injected with 2 μg estradiol and were killed 3 h later. Four, 24, 48, and 72 h after ganglionectomy, estradiol treatment induced 43–53% less accumulation of nuclear receptor-hormone complexes than that in controls, whereas the accumulation was 52% higher than that in controls during the expected degeneration of nerve terminals (i.e. 12 h after surgery). At this time, a minimal concentration of cytosol estrogen receptors was found. Injection of propranolol, but not of the α-adrenoceptor blocker phentolamine, to rats subjected to ganglionectomy 12 h earlier prevented the effect of estradiol. Rat pineals preincubated in vitro for 10 h failed to respond to subsequently added 10 nM estradiol with the increase in [¹⁴C] serotonin conversion to methoxyindoles found in untreated explants incubated with estradiol. Preincubated explants also exhibited 47% less accumulation of nuclear receptor-hormone complexes after exposure to estradiol. The addition of propranolol (but not of phentolamine) together with estradiol inhibited both the translocation of receptor-hormone complexes to nuclei and the stimulation of [¹⁴C] serotonin metabolism in vitro. These results indicate that in the pineal gland, the levels of cytoplasmic estrogen receptor and its translocation to the nucleus are under the control of sympathetic nerves via norepinephrine and β-adrenoceptors.