Neonatal gonadectomy and adult testosterone replacement suggest an involvement of limbic arginine vasopressin and androgen receptors in the organization of the hypothalamic-pituitary-adrenal axis
Neonatal gonadectomy and adult testosterone replacement suggest an involvement of limbic arginine vasopressin and androgen receptors in the organization of the hypothalamic-pituitary-adrenal axis
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DOI：
10.1210/en.2007-1796
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发表时间：
2008-07-01
期刊：
影响因子：
4.8
通讯作者：
Viau, Victor
中科院分区：
文献类型：
--
作者：
Bingham, Brenda;Viau, Victor
在发育的关键时期暴露于睾酮对下丘脑-垂体-肾上腺（HPA）轴产生主要的组织效应。在这里，我们研究了如何新生儿性腺切除术（GDX）与或不睾酮治疗在第一周的生活改变HPA反应成年睾酮替代65日龄的雄性大鼠。作为成年人，新生GDX大鼠表现出较高水平的血浆皮质酮和Fos激活的内侧小细胞部分室旁核的下丘脑在基础条件下，并在30分钟的约束曝光。这些反应正常化睾酮治疗出生后的第1-5天，但没有恢复与成人睾酮替代。作为成年人，新生GDX大鼠也表现出减少的雄激素受体和精氨酸加压素阳性细胞的数目在床核的终纹和杏仁核的内侧核，这两个反应与出生后睾酮治疗逆转。在强调和非强调的动物，雄激素受体和精氨酸加压素表达的神经元在这两个核的数量与血浆中的皮质酮浓度和室旁核的Fos水平呈负相关。两者合计，我们的研究结果表明，睾酮暴露在新生儿期引发成人HPA对睾酮的反应，通过改变雄激素受体水平和功能内的基础和应激相关的输入HPA轴的传入介质。
Testosterone exposure during critical periods of development exerts major organizing effects on the hypothalamic-pituitary-adrenal (HPA) axis. Here we examined how neonatal gonadectomy (GDX) with or without testosterone treatment during the first week of life alters the HPA response to adult testosterone replacement in 65-d-old male rats. As adults, neonatal GDX rats showed higher levels of plasma corticosterone and Fos activation in medial parvocellular part of the paraventricular nucleus of the hypothalamus under basal conditions and during 30 min of restraint exposure. These responses were normalized with testosterone treatment on postnatal d 1-5 but were not restored with adult testosterone replacement. As adults, neonatal GDX rats also showed a decrease in the number of androgen receptor and arginine vasopressin-positive cells in the bed nucleus of the stria terminalis and in the medial nucleus of the amygdala, and both of these responses were reversed with postnatal testosterone treatment. In stressed and unstressed animals, the number of androgen receptors and arginine vasopressin-expressing neurons in both of these nuclei correlated negatively with corticosterone concentrations in plasma and Fos levels in the paraventricular nucleus. Taken together, our findings suggest that testosterone exposure during the neonatal period primes the adult HPA response to testosterone by altering androgen receptor levels and function within afferent mediators of basal and stress-related input to the HPA axis.