Androgen Regulation of Corticotropin Releasing Factor Receptor 1 in the Mouse Brain.
Androgen Regulation of Corticotropin Releasing Factor Receptor 1 in the Mouse Brain.
复制标题
DOI：
10.1016/j.neuroscience.2022.04.005
复制
发表时间：
2022-05-21
期刊：
影响因子：
3.3
通讯作者：
Zuloaga, Damian G.
中科院分区：
文献类型：
--
作者：
Rybka, Krystyna A.;Sturm, Kassandra L.;De Guzman, Rose M.;Bah, Saoudatou;Jacobskind, Jason S.;Rosinger, Zachary J.;Taroc, Ed Zandro M.;Forni, Paolo E.;Zuloaga, Damian G.
关键词：
与压力相关的情绪障碍，如焦虑和抑郁，在女性中比男性更普遍，并且通常与下丘脑-垂体-肾上腺（HPA）轴失调有关。雄激素通过雄激素受体（AR）的作用降低HPA轴反应和应激相关行为。促肾上腺皮质激素释放因子（CRF）及其与CRF受体1（CRFR 1）的结合对于调节HPA轴、焦虑和抑郁也至关重要。我们首先确定了雄性和雌性CRFR 1-GFP小鼠中CRFR 1/AR共定位模式。在室旁核（PVN）、终纹床核的背外侧和前腹侧分区（BSTdl和BSTav）、内侧视前区（MPOA）和后背内侧杏仁核（MePD）内发现了高共定位。接下来，我们确定了非芳香化雄激素双氢睾酮（DHT）是否调节CRFR 1表达和应激诱导的CRFR 1表达细胞活化。在PVN中，CRFR 1-GFP细胞数量在性腺切除术（GDX）后减少，但DHT治疗逆转了这种效应。与性腺完整和GDX未处理组相比，GDX-DHT处理的小鼠在BSTdl内也具有减少的CRFR 1-GFP细胞数。与性腺完整和GDX-DHT组相比，束缚应激后，GDX空白小鼠MePD中的c-Fos/CRFR 1共定位神经元较少，表明GDX后应激诱导的CRFR 1神经元活化减少。在GDX雄性动物中发现了更高的血浆皮质酮（CORT），与GDX-DHT和假雄性动物相比，在束缚应激后，PVN CRFR 1+神经元和皮质酮水平之间呈负相关，在束缚后30分钟和90分钟。这些研究结果表明，雄激素可以直接改变大脑中CRFR 1的水平，这可能与HPA轴调节和压力相关行为的性别差异有关。
Stress-related mood disorders like anxiety and depression are more prevalent in women than men and are often associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Androgen actions through androgen receptors (ARs) decrease HPA axis responses and stress-associated behaviors. Corticotropin releasing factor (CRF) and its binding to CRF receptor 1 (CRFR1) is also critical for regulation of the HPA axis, anxiety, and depression. We first determined CRFR1/AR co-localization patterns in male and female CRFR1-GFP mice. High co-localization was found within the paraventricular nucleus (PVN), dorsolateral and anteroventral subdivisions of the bed nucleus of the stria terminalis (BSTdl and BSTav), medial preoptic area (MPOA), and posterodorsal medial amygdala (MePD). We next determined whether the non-aromatizable androgen dihydrotestosterone (DHT) regulates CRFR1 expression and stress-induced activation of CRFR1-expressing cells. In the PVN, CRFR1-GFP cell number decreased following gonadectomy (GDX), but DHT treatment reversed this effect. GDX-DHT treated mice also had a decreased CRFR1-GFP cell number within the BSTdl compared to gonad intact and GDX-untreated groups. Following restraint stress GDX-blank mice showed fewer c-Fos/CRFR1 co-localized neurons in the MePD compared to gonad intact and GDX-DHT groups indicating decreased stress-induced activation of CRFR1 neurons following GDX. Higher plasma corticosterone (CORT) was found in GDX males compared to GDX-DHT and sham males following restraint stress, with a negative correlation between PVN CRFR1+ neurons and corticosterone levels 30- and 90-minutes following restraint. Together these findings show androgens can directly alter CRFR1 levels in the brain which may have implications for sex differences in regulation of the HPA axis and stress-related behaviors.
登录
查看更多内容
影响因子：
3.2
作者：
Handa RJ;Weiser MJ;Zuloaga DG
通讯作者：
Zuloaga DG
影响因子：
3.7
作者：
Cooper MA;Clinard CT;Dulka BN;Grizzell JA;Loewen AL;Campbell AV;Adler SG
通讯作者：
Adler SG
影响因子：
5
作者：
Jiang, Zhiying;Rajamanickam, Shivakumar;Justice, Nicholas J.
通讯作者：
Justice, Nicholas J.
影响因子：
5.8
作者：
Frimodt-Moller, Katrine Emilie;Jepsen, Jens Richardt Mollegaard;Krogh, Jesper
通讯作者：
Krogh, Jesper
影响因子：
2.7
作者：
Jacobskind, Jason S.;Rosinger, Zachary J.;Zuloaga, Damian G.
通讯作者：
Zuloaga, Damian G.