Estrogen modulation of adrenoceptor responsiveness in the female rat pineal gland: differential expression of intracellular estrogen receptors
The effect of different doses of 17β-estradiol (E2) on the pineal response to β-adrenoceptor stimulation in female rats was examined. Pinealocytes from 21-day-old ovariectomized rats were exposed to different estrogen doses and treated with β-adrenergic agonists. Estrogen treatment produced a dose-dependent, biphasic response to β-adrenoceptor-induced accumulation of cAMP. This effect was inhibitory at estrogen doses up to 0.1 nmand fitted to a negative exponential curve, while at doses from 0.1 to 100 nmthe effect was stimulatory and fitted to a standard positive hyperbola. For in vivo studies, ovariectomized rats were treated with equivalent estrogen concentrations plus a single dose of progesterone (250 g per rat), and their pineals exposed in vitro to β-adrenergic agonists. Low doses of E2 (0.1–100 ng per rat) reduced both pineal cAMP accumulation and N-acetyltransferase activity after β-adrenoceptor stimulation, while a high dose (10 g per rat) induced the opposite response. Apparently, the final estrogen target was the pineal β-adrenergic receptor, as a low dose of E2 (which had diminished cAMP accumulation after β-adrenoceptor stimulation) also reduced its maximal binding capacity (Bmax) and its dissociation constant (Kd). We also found that the female rat pineal gland contains two different ER subtypes, α and β, which respond to estrogen exposure with nucleocytoplasmic shuttling. These results indicate that, in the female rat, estrogen directly modulates pineal sensitivity to adrenergic stimulation in a complex, dose-dependent manner that may be related to differential expression and activity of two estrogen receptor subtypes within pineal cells.
Document Type: Research Article
Affiliations: 1: Physiology (Laboratory of Cellular Neurobiology) 2: Anatomy 3: Institute of Toxicology, University of La Laguna School of Medicine and Institute of Biomedical Technologies, La Laguna, Sta Cruz de Tenerife 4: Department of Biostatistics, University Complutense School of Medicine, Madrid, Spain
Publication date: August 1, 2004