A Subset of Estrogen Receptor‐Containing Neurons Project to the Median Eminence in the Ewe

The neural pathways responsible for conveying the steroid feedback signals that ultimately affect reproductive neuroendocrine function remain largely undefined. One possibility involves a direct projection from estrogen receptor (ER)-containing neurons to the median eminence (ME), a site of neuroendocrine peptide release. To examine this possibility, 8 ewes received stereotaxic injections of the retrograde neuronal tract-tracing compound cholera toxin-beta subunit (CT beta) into the ME. Neurons sending projections to the ME and containing ER were identified using a dual-label immunoperoxidase method. Double-labeled cells were found in distinct regions: (1) the ER-rich arcuate nucleus (ARC) that contained the greatest number of double-labeled cells, and (2) the organum vasculosum of the lamina terminalis (OVLT) which contained a very consistent, but low, number of double-labeled cells. While a fairly large number of retrogradely-labeled ARC neurons containing ER were identified, the majority of ER-containing ARC neurons were unlabeled and thus send projections elsewhere. Other regions containing high concentrations of ER-positive cells such as the medial preoptic area (MPOA), anterior hypothalamic area, and ventrolateral portion of the ventromedial hypothalamic nucleus, were devoid of double-labeled cells. Similarly, regions rich in neuroendocrine neurons such as the periventricular hypothalamus and paraventricular and supraoptic hypothalamic nuclei contained no double-labeled cells. These results suggest that modulation of neuroendocrine secretory activity may occur directly at the level of the ME by ER-containing neurons located within restricted regions of the hypothalamus and forebrain. However, the relatively low proportion of ER-containing neurons projecting to the ME suggests that the influence of estradiol upon neuroendocrine function also may include target sites other than the ME.