Estrogen desensitizes 5-HT1A receptors and reduces levels of Gz, Gi1 and Gi3 proteins in the hypothalamus
Estrogen desensitizes 5-HT1A receptors and reduces levels of Gz, Gi1 and Gi3 proteins in the hypothalamus
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DOI：
10.1016/s0028-3908(99)00264-6
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Van de Kar, LD
中科院分区：
文献类型：
--
作者：
Raap, DK;DonCarlos, L;Van de Kar, LD
The present study investigated whether estrogen would desensitize hypothalamic serotonin(1A) (5-HT1A) receptors by examining the neuroendocrine response to 8-OH-DPAT, a 5-HT1A agonist. Rats were ovariectomized, allowed to recover for 5 days, then given 2 daily injections of estradiol benzoate or vehicle (10 mu g/day, s.c.). Twenty-four hours after the second injection, rats were challenged with a sub-maximal dose of 8-OH-DPAT (50 mu g/kg, sc) or saline 15 min prior to sacrifice. 8-OH-DPAT produced a significant increase in plasma oxytocin, ACTH and corticosterone levels in ovariectomized rats. While estrogen treatment for 2 days did not alter basal hormone levels, it did significantly reduce the magnitude of oxytocin, ACTH and corticosterone responses to 8-OH-DPAT, The reduction in hormone responses was accompanied by a significant reduction in hypothalamic levels of G(z), G(il) and G(i3) proteins (by 50%, 30% and 50%, respectively). These findings suggest that a reduction in these G proteins may contribute to the mechanisms underlying estrogen-induced desensitization of 5-HT1A receptors. The desensitization of 5-HT1A receptors has been suggested to underlie the therapeutic effects of antidepressant 5-HT uptake inhibitors (SSRIs). Thus, the present results suggest that estrogen or estrogen-like substances in combination with SSRIs may prove effective in developing novel therapeutic strategies for neuropsychiatric disorders in women. (C) 2000 Elsevier Science Ltd. All rights reserved.
