Modulation of responses to stress by estradiol benzoate and selective estrogen receptor agonists.
Modulation of responses to stress by estradiol benzoate and selective estrogen receptor agonists.
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DOI:
10.1677/joe-10-0029
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发表时间:
2010-06
期刊:
影响因子:
--
通讯作者:
Sabban EL
中科院分区:
文献类型:
--
作者:
Serova LI;Harris HA;Maharjan S;Sabban EL
Previously, pretreatment with estradiol benzoate (EB) was found to modulate response of HPA axis and gene expression in several catecholaminergic neuronal locations in ovariectomized (OVX) rats exposed to single immobilization stress (IMO). Here, we investigated the role of estrogen receptor (ER) subtypes, using selective agonists for ERα (PPT) or ERβ (WAY-200070) in two major central noradrenergic systems and the HPA axis after exposure to single and repeated IMO. OVX female rats received 21 daily injections of either EB (25 μg/kg), PPT (10 mg/kg), WAY-200070 (10 mg/kg) or vehicle. Injections of EB and PPT, but not WAY-200070, elicited reduced body weight and increased uterine weight, showing their selectivity. Both EB and PPT increased corticosterone levels about 2-3 fold, but prevented any further rise with either single or repeated IMO, indicating an ERα, but not ERβ, mediated mechanism. In the locus coeruleus (LC), the rise in dopamine-β-hydroxylase (DBH) mRNA with both stress paradigms was abrogated in EB or PPT injected animals. However, WAY-200070 blocked response of DBH mRNA to single but not repeated IMO. In the nucleus of the solitary tract (NTS), the rise in tyrosine hydroxylase (TH) and DBH mRNAs with both IMOs was absent, or greatly attenuated, in EB or PPT treated rats. In most cases, WAY-200070 inhibited the response to single but not repeated IMO. The results demonstrate that pretreatment with estradiol, or ER selective agonists, modulate the stress-triggered induction of gene expression of norepinephrine biosynthetic enzymes in LC and NTS, with ER selectivity depending on duration of the stress.