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Estrogen modulation of adrenoceptor responsiveness in the female rat pineal gland: differential expression of intracellular estrogen receptors
Author(s) -
Sànchez Juan J.,
Abreu Pedro,
GonzálezHernández Tomás,
Hernández Alexis,
Prieto Luis,
Alonso Rafael
Publication year - 2004
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2004.00132.x
Subject(s) - endocrinology , medicine , estrogen , stimulation , ovariectomized rat , pineal gland , pinealocyte , estrogen receptor , biology , adrenergic receptor , receptor , melatonin , cancer , breast cancer
The effect of different doses of 17 β ‐estradiol (E 2 ) 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 n m and fitted to a negative exponential curve, while at doses from 0.1 to 100 n m 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 μ g per rat), and their pineals exposed in vitro to β ‐adrenergic agonists. Low doses of E 2 (0.1–100 ng per rat) reduced both pineal cAMP accumulation and N‐acetyltransferase activity after β ‐adrenoceptor stimulation, while a high dose (10 μ g per rat) induced the opposite response. Apparently, the final estrogen target was the pineal β ‐adrenergic receptor, as a low dose of E 2 (which had diminished cAMP accumulation after β ‐adrenoceptor stimulation) also reduced its maximal binding capacity ( B max ) and its dissociation constant ( K d ). 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.