Localization of estrogen-receptive neurons projecting to the GnRH neuron-containing rostral preoptic area of the ewe

Estrogen exerts important feedback effects upon the biosynthetic and secret ory behavior of gonadotropin-releasing hormone (GnRH) neurons to control re productive functioning. The mechanism of estrogen action upon these neurons is unclear and seems likely to involve the transsynaptic regulation of GnR H neurons. The objective of the present study was to identify the estrogen- receptive neural populations which project to the general vicinity of the G nRH perikarya in the rostral preoptic area and diagonal band of Broca (rPOA /DBB) of the ewe. Intact breeding-season ewes received an injection of the retrograde tracer fluorogold (FG) into the rPOA/DBB, and their hypothalami and brainstems examined for the presence of FG and estrogen receptor alpha (ER alpha) immunocytochemistry. Retrogradely labeled neurons were identifie d principally within the lateral septum (LS), lamina terminalis, bed nucleu s of the stria terminalis, POA, arcuate nucleus (ARN), ventromedial nucleus (VMN) and median eminence. Smaller numbers of FG-immunoreactive cells were found in the caudal brainstem where they resided mostly in the ventrolater al medulla (VLM). Dual-labeled cells exhibiting both FG and ERa staining we re prominent in the POA, LS and at all rostrocaudal levels of the VMN and A RN. Small numbers of dual-labeled cells were found in the VLM. These observ ations indicate that a number of distinct ER alpha-expressing neural popula tions project to the rPOA/DBB where the majority of the GnRH perikarya are found in the ewe. Although it is not possible to determine the direct conne ctivity of these projections with GnRH neurons, the findings provide an ini tial neuroanatomical framework through which the transsynaptic actions of e strogen on ovine GnRH neurons may be tested.