Sànchez Juan J, Abreu Pedro, González-Hernández Tomás, Hernández Alexis, Prieto Luis, Alonso Rafael
Department of Physiology (Laboratory of Cellular Neurobiology), University of La Laguna School of Medicine and Institute of Biomedical Technologies, La Laguna, Sta Cruz de Tenerife, Spain.
J Pineal Res. 2004 Aug;37(1):26-35. doi: 10.1111/j.1600-079X.2004.00132.x.
The effect of different doses of 17beta-estradiol (E2) on the pineal response to beta-adrenoceptor stimulation in female rats was examined. Pinealocytes from 21-day-old ovariectomized rats were exposed to different estrogen doses and treated with beta-adrenergic agonists. Estrogen treatment produced a dose-dependent, biphasic response to beta-adrenoceptor-induced accumulation of cAMP. This effect was inhibitory at estrogen doses up to 0.1 nM and fitted to a negative exponential curve, while at doses from 0.1 to 100 nM the 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 microg per rat), and their pineals exposed in vitro to beta-adrenergic agonists. Low doses of E2 (0.1-100 ng per rat) reduced both pineal cAMP accumulation and N-acetyltransferase activity after beta-adrenoceptor stimulation, while a high dose (10 microg per rat) induced the opposite response. Apparently, the final estrogen target was the pineal beta-adrenergic receptor, as a low dose of E2 (which had diminished cAMP accumulation after beta-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, alpha and beta, 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.
研究了不同剂量的17β-雌二醇（E2）对雌性大鼠松果体对β-肾上腺素能受体刺激反应的影响。将21日龄去卵巢大鼠的松果体细胞暴露于不同剂量的雌激素，并给予β-肾上腺素能激动剂处理。雌激素处理对β-肾上腺素能受体诱导的环磷酸腺苷（cAMP）积累产生剂量依赖性的双相反应。在雌激素剂量高达0.1 nM时，这种作用具有抑制性，符合负指数曲线，而在0.1至100 nM的剂量下，作用具有刺激性，符合标准正双曲线。对于体内研究，去卵巢大鼠用等效的雌激素浓度加单剂量孕酮（每只大鼠250微克）处理，然后将其松果体在体外暴露于β-肾上腺素能激动剂。低剂量的E2（每只大鼠0.1 - 100 ng）在β-肾上腺素能受体刺激后降低了松果体cAMP积累和N-乙酰转移酶活性，而高剂量（每只大鼠10微克）则诱导了相反的反应。显然，雌激素的最终作用靶点是松果体β-肾上腺素能受体，因为低剂量的E2（在β-肾上腺素能受体刺激后降低了cAMP积累）也降低了其最大结合容量（Bmax）和解离常数（Kd）。我们还发现雌性大鼠松果体含有两种不同的雌激素受体亚型，α和β，它们对雌激素暴露的反应是核质穿梭。这些结果表明，在雌性大鼠中，雌激素以复杂的、剂量依赖性的方式直接调节松果体对肾上腺素能刺激的敏感性，这可能与松果体细胞内两种雌激素受体亚型的差异表达和活性有关。
