Oyola Mario G, Handa Robert J
a Department of Biomedical Sciences , Colorado State University , Fort Collins , CO , USA.
Stress. 2017 Sep;20(5):476-494. doi: 10.1080/10253890.2017.1369523. Epub 2017 Aug 31.
Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.
性腺激素在下丘脑 - 垂体 - 肾上腺（HPA）轴的建立、激活和调节中起关键作用。通过影响对释放因子、神经递质和激素的反应及敏感性，性腺类固醇有助于协调HPA轴的增益，以微调全身循环中应激激素的水平。从幼年到成年，性腺类固醇可对HPA轴产生不同影响，导致该轴反应性出现性别差异。HPA轴影响许多生理功能，使生物体对环境变化的反应与其生殖状态相适应。虽然HPA对压力源的急性反应是一种有益反应，但慢性或创伤性应激事件持续激活该神经回路可能导致HPA轴失调并引发病理状况。与雄性相比，雌性小鼠和大鼠表现出更强的HPA轴反应，这是由于循环雌二醇水平在非威胁性情况下以及应激源期间和之后会升高应激激素水平。雌性在发情周期中性腺类固醇水平的波动是导致其HPA活性强度与雄性相比存在性别差异的主要因素。此外，性腺类固醇甚至在青春期前可能也会对HPA轴产生表观遗传和组织学影响。相应地，下丘脑 - 垂体 - 性腺（HPG）轴与HPA轴之间的相互作用可能导致应激反应异常。在人类中，应激反应失调是许多神经精神疾病中最常见的症状之一，因此，这种相互作用可能会加剧外周病理学状况。在本综述中，我们讨论HPA轴和HPG轴，并回顾性腺类固醇如何与HPA轴相互作用以在生命的各个阶段调节应激神经回路。
