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17β-雌二醇间接抑制雌性大鼠下丘脑室旁核内促甲状腺素释放激素的表达,并削弱甲状腺轴对寒冷暴露的反应。

17β-Oestradiol indirectly inhibits thyrotrophin-releasing hormone expression in the hypothalamic paraventricular nucleus of female rats and blunts thyroid axis response to cold exposure.

机构信息

Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

出版信息

J Neuroendocrinol. 2009 May;21(5):439-48. doi: 10.1111/j.1365-2826.2009.01861.x.

DOI:10.1111/j.1365-2826.2009.01861.x
PMID:19302192
Abstract

Energy expenditure and thermogenesis are regultated by thyroid and sex hormones. Several parameters of hypothalamic-pituitary-thyroid (HPT) axis function are modulated by 17β-oestradiol (E(2)) but its effects on thyrotrophin-releasing hormone (TRH) mRNA levels remain unknown. We evaluated, by in situ hybridisation and Northern bloting, TRH expression in the paraventricular nucleus of the hypothalamus (PVN) of cycling rats, 2 weeks-ovariectomised (OVX) and OVX animals injected s.c. during 1-4 days with E(2) (5, 50, 100 or 200 μg ⁄ kg) (OVX-E). Serum levels of E(2), thyroid-stimulating hormone (TSH), prolactin, corticosterone and triiodothyronine (T(3)) were quantified by radioimmunoassay. Increased serum E(2) levels were observed after 4 days injection of 50 μg ⁄ kg E(2) (to 68.5 ± 4.8 pg ⁄ ml) in OVX rats. PVN-TRH mRNA levels were slightly higher in OVX than in virgin females at dioestrous 1 or pro-oestrous, decreasing proportionally to increased serum E(2) levels. E(2) injections augmented serum T(3), prolactin, and corticosterone levels. Serum TSH levels augmented with 4 days 50 μg ⁄ kg E(2), but not with the higher doses that enhanced serum T(3) levels. Exposure to cold for 1 h resulted in marked HPT axis activation in OVX rats, increasing the levels of TRH mRNA along the rostro-caudal PVN areas, as well as serum TSH, T(3), corticosterone and prolactin levels. By contrast, no significant changes in any of these parameters were observed in cold-exposed OVX-E (50 μg ⁄ kg E(2)) rats. Very few PVN-TRHergic neurones expressed the oestrogen receptor type-α, suggesting that the effects of E(2) on PVN-TRH expression are indirect, most probably as a result of its multiple modulatory effects on circulating hormones and their receptor sensitivity. The blunted response of OVX-E rats to cold coincides with the effects of E(2) on the autonomic nervous system and increased cold tolerance.

摘要

能量消耗和产热受甲状腺和性激素调节。几种下丘脑-垂体-甲状腺(HPT)轴功能的参数受 17β-雌二醇(E2)调节,但它对促甲状腺素释放激素(TRH)mRNA 水平的影响尚不清楚。我们通过原位杂交和 Northern blot 评估了发情周期大鼠、2 周卵巢切除(OVX)大鼠和皮下注射 E2(5、50、100 或 200μg/kg)(OVX-E)1-4 天的下丘脑室旁核(PVN)中的 TRH 表达。用放射免疫法测定血清 E2、促甲状腺激素(TSH)、催乳素、皮质酮和三碘甲状腺原氨酸(T3)水平。OVX 大鼠注射 50μg/kg E2 4 天后,血清 E2 水平升高(至 68.5±4.8pg/ml)。OVX 大鼠发情期 1 天或发情前期的 PVN-TRH mRNA 水平略高于未交配的雌性,且与血清 E2 水平成正比。E2 注射增加了血清 T3、催乳素和皮质酮水平。血清 TSH 水平随着 4 天 50μg/kg E2 的注射而升高,但随着血清 T3 水平升高的较高剂量则不会升高。暴露于寒冷 1 小时会导致 OVX 大鼠 HPT 轴明显激活,增加沿 PVN 区的 TRH mRNA 水平,以及血清 TSH、T3、皮质酮和催乳素水平。相比之下,暴露于寒冷的 OVX-E(50μg/kg E2)大鼠中,这些参数没有明显变化。很少有 PVN-TRH 能神经元表达雌激素受体-α,这表明 E2 对 PVN-TRH 表达的影响是间接的,很可能是由于其对循环激素及其受体敏感性的多种调节作用。OVX-E 大鼠对寒冷的反应迟钝与 E2 对自主神经系统的影响和增加的耐寒性相吻合。

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