Scott C J, Rawson J A, Pereira A M, Clarke I J
Department of Physiology, Monash University, Clayton, Vic, Australia.
J Neuroendocrinol. 1999 Oct;11(10):745-55. doi: 10.1046/j.1365-2826.1999.00370.x.
Oestrogen regulates the secretion of gonadotropin releasing hormone (GnRH) and this could be mediated by noradrenergic systems originating in the brainstem. Whilst it is known that noradrenergic cells possess oestrogen receptors (ER), it is not known whether ER-immunoreactive (-ir) cells in the brainstem project to the regions of the hypothalamus in which GnRH neurons are found. We have used dual-label immunocytochemistry to determine the extent to which ER-alpha is found in noradrenergic cells in the brainstem of the ovariectomized (OVX) ewe. Noradrenergic/adrenergic cells were identified by immunostaining for dopamine beta-hydroxylase (DBH). Cells that stained for both DBH and ER were found in both the A1 and A2 cell groups, with the highest levels found in the most caudal regions. In the A1 group, at the most caudal extent, 73% of ER-ir cells were DBH-positive and 19% of DBH-ir cells were ER-positive. The degree of co-localization decreased in a linear manner towards the rostral brainstem. In the caudal half of A2, 9-14% of ER-ir cells were DBH-positive and 20-25% of DBH cells were ER-positive. Less than 2% of DBH-ir cells in the A5 group were dual-labelled and none of the cells in the A6 and A7 groups were ER-positive. The retrograde tracer FluoroGold was injected into the preoptic area of nine OVX ewes and labelled cells were examined in the brainstem to determine the extent of co-localization of ER. Only injections in the rostroventral part of the medial preoptic area near to the organum vasculosum of the lamina terminalis resulted in the labelling of cells in the brainstem. One ewe with very strong labelling of the brainstem was selected for detailed mapping. In the ventrolateral medulla, half the ER-ir cells in the most caudal regions were retrogradely labelled. Almost all the ER-ir cells in the mid-region of the ventrolateral medulla were retrogradely labelled but no co-localization of retrograde tracer and ER was observed rostral to obex. There were many ER-ir cells and retrogradely-labelled cells in the nucleus of the solitary tract but only a few double-labelled cells. Similarly, numerous ER-ir cells and retrogradely labelled cells were observed around the lateral edges of the caudal fourth ventricle and across to the lateral parabrachial nucleus but there were few double-labelled cells. These results suggest differential regulation of noradrenergic cells by oestrogen, with a direct action of the hormone confined to the cells in the most caudal region of the A1 and A2 cell groups. The cells of the caudal ventrolateral medulla which contain ER-ir cells that project to the preoptic area may be important in the mediation by noradrenaline of the actions of oestrogen on GnRH secretion in the ewe.
雌激素调节促性腺激素释放激素（GnRH）的分泌，这可能由源自脑干的去甲肾上腺素能系统介导。虽然已知去甲肾上腺素能细胞具有雌激素受体（ER），但尚不清楚脑干中ER免疫反应性（-ir）细胞是否投射到发现GnRH神经元的下丘脑区域。我们使用双重标记免疫细胞化学来确定在去卵巢（OVX）母羊脑干的去甲肾上腺素能细胞中发现ER-α的程度。通过对多巴胺β-羟化酶（DBH）进行免疫染色来鉴定去甲肾上腺素能/肾上腺素能细胞。在A1和A2细胞组中均发现了同时对DBH和ER染色的细胞，在最尾端区域含量最高。在A1组的最尾端，73%的ER-ir细胞为DBH阳性，19%的DBH-ir细胞为ER阳性。共定位程度朝着脑干头端呈线性下降。在A2的尾侧半部，9%-14%的ER-ir细胞为DBH阳性，20%-25%的DBH细胞为ER阳性。A5组中不到2%的DBH-ir细胞为双重标记，A6和A7组中没有细胞为ER阳性。将逆行示踪剂荧光金注射到9只OVX母羊的视前区，并检查脑干中标记的细胞以确定ER的共定位程度。仅在内侧视前区靠近终板血管器的头腹侧部分注射才导致脑干中细胞被标记。选择一只脑干标记非常强烈的母羊进行详细绘图。在腹外侧延髓，最尾端区域一半的ER-ir细胞被逆行标记。腹外侧延髓中部几乎所有的ER-ir细胞都被逆行标记，但在闩前方未观察到逆行示踪剂与ER的共定位。孤束核中有许多ER-ir细胞和逆行标记细胞，但只有少数双重标记细胞。同样，在尾侧第四脑室的外侧边缘周围以及横跨到外侧臂旁核观察到大量ER-ir细胞和逆行标记细胞，但双重标记细胞很少。这些结果表明雌激素对去甲肾上腺素能细胞有不同的调节作用，该激素的直接作用局限于A1和A2细胞组最尾端区域的细胞。含有投射到视前区的ER-ir细胞的尾侧腹外侧延髓细胞可能在去甲肾上腺素介导雌激素对母羊GnRH分泌的作用中起重要作用。
