McCormick C M, Furey B F, Child M, Sawyer M J, Donohue S M
Neuroscience Program, Bates College, Lewiston, Maine 04240, USA.
Brain Res Dev Brain Res. 1998 Feb 10;105(2):295-307. doi: 10.1016/s0165-3806(97)00155-7.
Sex hormones have activational effects on the hypothalamic-pituitary-adrenal (HPA) axis in adulthood: For example, corticosterone release is influenced by gonadal status. These experiments investigated whether sex hormones have organizational effects on the HPA axis of male rats: Do sex hormones have relatively permanent effects on its development? In adults, both neonatal (neoGDX) and adult gonadectomy (adult GDX) resulted in elevated corticosterone (CORT) levels in response to stress compared to intact rats. Five days of testosterone propionate (TP) replacement was not as effective at attenuating CORT levels in neoGDX rats as in adult GDX rats. Neonatal GDX elevated corticosterone binding globulin (CBG) levels, whereas adult GDX was without effect. In Experiment 2 the effects of neonatal gonadectomy and neonatal treatment with either TP, estradiol benzoate (EB), or oil vehicle was examined. Despite 14 days of hormone replacement, neoGDX showed elevated CORT levels in response to stress compared to all other groups. A single neonatal dose of TP or EB in neoGDX rats eliminated the increased responsiveness. Neonatal TP and EB were without effect in sham-operated rats. Plasma CBG levels were elevated in neoGDX groups regardless of neonatal hormone treatment. Corticosteroid receptor binding levels were examined in various brain areas and the pituitary in two groups most different in their androgen experience: NeoGDX and shams that did not receive treatments as adults. NeoGDX had lower levels of glucocorticoid receptor, and higher levels of mineralocorticoid receptor binding in the pituitary. No other receptor differences were found. These experiments suggest that neonatal sex hormones influence the sensitivity of the HPA axis to sex hormones in adulthood and, thus, that they have organizational effects in addition to activational effects on HPA function.
性激素在成年期对下丘脑-垂体-肾上腺（HPA）轴具有激活作用：例如，皮质酮的释放受性腺状态的影响。这些实验研究了性激素对雄性大鼠HPA轴是否具有组织效应：性激素对其发育是否具有相对持久的影响？在成年大鼠中，与未阉割的大鼠相比，新生期去势（neoGDX）和成年期去势（成年GDX）都会导致应激状态下皮质酮（CORT）水平升高。丙酸睾酮（TP）替代治疗5天，在减轻neoGDX大鼠的CORT水平方面不如成年GDX大鼠有效。新生期去势会升高皮质酮结合球蛋白（CBG）水平，而成年期去势则无此作用。在实验2中，研究了新生期去势以及新生期用TP、苯甲酸雌二醇（EB）或油性赋形剂处理的效果。尽管进行了14天的激素替代治疗，但与所有其他组相比，neoGDX大鼠在应激状态下仍表现出升高的CORT水平。在neoGDX大鼠中，新生期单次给予TP或EB可消除反应性增加的现象。新生期TP和EB对假手术大鼠无影响。无论新生期激素处理如何，neoGDX组的血浆CBG水平均升高。在雄激素经历差异最大的两组中，即新生期去势组和成年后未接受治疗的假手术组，检测了不同脑区和垂体中的糖皮质激素受体结合水平。新生期去势组的垂体中糖皮质激素受体水平较低，盐皮质激素受体结合水平较高。未发现其他受体差异。这些实验表明，新生期性激素会影响成年期HPA轴对性激素的敏感性，因此，它们除了对HPA功能具有激活作用外，还具有组织效应。
