Patchev V K, Hayashi S, Orikasa C, Almeida O F
Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Stress. 1999 Aug;3(1):41-54. doi: 10.3109/10253899909001111.
The neuroendocrine response to stress in the rat displays gender-specific characteristics resulting from both sex hormone-dependent organization of neuroendocrine regulatory mechanisms and the modulatory action of circulating gonadal steroids. To define the role of gonadal steroid-mediated brain differentiation in the emergence of sex-specific differences in pituitary-adrenal function, and the necessity of physiological gonadal secretions for the manifestation of these differences, we examined the ontogeny of diurnal and stress-induced corticosterone (B) secretion, and suppressibility of the latter by dexamethasone (DEX) in intact male and female rats, and in animals that were subject to neonatal manipulations of the gonadal steroid environment (orchidectomy in males and neonatal estrogenization in females). Further, gene expression of corticosteroid receptors (MR and GR), corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) under basal conditions, and following adrenalectomy (ADX) and chronic supplementation with high doses of B, were investigated in adult male and female rats, and individuals of both sexes which have been exposed to alterations of the gonadal steroid milieu during early development. The results demonstrate that: i) gender-specific differences in basal and stress-induced adrenocortical secretion are present at birth, but are still maleable by neonatal alterations of the gonadal steroid environment; ii) gender-specific dichotomy in the sensitivity of the secretory stress response to glucocorticoid feedback becomes fully manifest in adulthood; iii) sex differences in basal adrenocortical secretion become fully expressed only in the presence of intact gonads, whereas, once established by the neonatal hormonal milieu, differential sensitivity of the stress response to glucocorticoids persists in the absence of functioning gonads; iv) neonatal hormone manipulations alter sex-specific characteristics of CRH, AVP, MR and GR gene expression in the brain, and the changes persist in adulthood independently of gonadal secretions; v) regulation of CRH gene expression by glucocorticoids displays gender-specific patterns which are probably established during the period of sex hormone-dependent brain organization and their manifestation does not require physiological gonadal secretions in adulthood.
大鼠对应激的神经内分泌反应表现出性别特异性特征，这是由神经内分泌调节机制的性激素依赖性组织以及循环性腺类固醇的调节作用共同导致的。为了确定性腺类固醇介导的脑分化在垂体 - 肾上腺功能性别特异性差异出现中的作用，以及生理性性腺分泌对于这些差异表现的必要性，我们研究了完整雄性和雌性大鼠以及性腺类固醇环境受到新生期操作（雄性去势和雌性新生期雌激素化）的动物中，昼夜和应激诱导的皮质酮（B）分泌的个体发生，以及地塞米松（DEX）对后者的抑制作用。此外，还研究了成年雄性和雌性大鼠以及在早期发育过程中性腺类固醇环境发生改变的两性个体在基础条件下、肾上腺切除（ADX）后以及高剂量B长期补充后的皮质类固醇受体（MR和GR）、促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）的基因表达。结果表明：i）基础和应激诱导的肾上腺皮质分泌的性别特异性差异在出生时就存在，但可通过性腺类固醇环境的新生期改变而改变；ii）分泌应激反应对糖皮质激素反馈的敏感性的性别特异性二分法在成年期完全显现；iii）基础肾上腺皮质分泌的性别差异仅在性腺完整时才完全表达，而一旦由新生期激素环境建立，应激反应对糖皮质激素的差异敏感性在性腺无功能时仍持续存在；iv）新生期激素操作改变了脑中CRH、AVP、MR和GR基因表达的性别特异性特征，且这些变化在成年期持续存在，与性腺分泌无关；v）糖皮质激素对CRH基因表达的调节表现出性别特异性模式，这可能在性激素依赖性脑组织形成期间建立，且其表现在成年期不需要生理性性腺分泌。
