Oestrogen receptors in the brainstem of the female sheep: Relationship to noradrenergic cells and cells projecting to the medial preoptic area

Oestrogen regulates the secretion of gonadotropin releasing hormone (GnRH) and this could be mediated by noradrenergic systems originating in the brai nstem. Whilst it is known that noradrenergic cells possess oestrogen recept ors (ER), it is not known whether ER-immunoreactive (-ir) cells in the brai nstem 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 o variectomized (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 high est levels found in the most caudal regions, In the A1 group, at the most c audal 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 manne r towards the rostral brainstem, In the caudal half of A2, 9-14% of ER-ir c ells 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 we re examined in the brainstem to determine the extent of co-localization of ER, Only injections in the rostroventral part of the medial preoptic area n ear to the organum vasculosum of the lamina terminalis resulted in the labe lling 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 retrograde ly-labelled cells in the nucleus of the solitary tract but only a few doubl e-labelled cells. Similarly, numerous ER-ir cells and retrogradely labelled cells were observed around the lateral edges of the caudal fourth ventricl e and across to the lateral parabrachial nucleus but there were few double- labelled cells. These results suggest differential regulation of noradrener gic 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 th e actions of oestrogen on GnRH secretion in the ewe.