Two populations of luteinizing hormone-releasing hormone neurons in the forebrain of the rhesus macaque during embryonic development

Abstract

To investigate the possibility that a second luteinizing hormone-releasing hormone (LHRH) population appears during development in primates, embryos and fetal brains of rhesus monkeys were immunostained with antisera specific to different LHRH forms. Two LHRH cell populations were discernible by immunoreactivity to antisera LR-1 and GF-6. Because one LHRH cell type migrated out from the olfactory placode several days earlier than the other, they were referred to as "early" and "late" LHRH cells, respectively. Although late LHRH neurons were immunoreactive to all anti-mammalian LHRH antisera tested, early LHRH neurons were only detected by antiserum GF-6. Early LHRH neurons (approximately 10 x 7 microm) were smaller than late LHRH neurons (approximately 18 x 7 microm). Early LHRH neurons were first found around the olfactory placode, in the nasal mesenchyme, and in the rostroventral forebrain on embryonic day 30 (E30), whereas late LHRH neurons were first seen in the olfactory pit on E32. Early LHRH cells were located throughout the basal forebrain on E32-E42, whereas late LHRH cells were found in the olfactory pit and along the terminal nerve on E34-E36 and were not seen in the forebrain until E38. By E51-E62, late LHRH neurons reached into the basal hypothalamus in a distribution resembling that in the older brain, while early LHRH neurons were found in the septum, preoptic region, stria terminalis, medial amygdala, claustrum, internal capsule, and globus pallidus. Based on the distribution pattern of immunopositive cells with antiserum LR-1, late LHRH cells are bona fide LHRH neurons that regulate the pituitary-gonadal axis. In contrast, the molecular form of early LHRH cells is unclear, although it is plausible that early LHRH cells may contain the molecule in which the C-terminal epitope of LHRH is modified or absent. It is concluded that in primates there is a second population of LHRH neurons that originates from the embryonic olfactory placode before the origin of mammalian LHRH-like neurons, and that these two populations of LHRH-immunopositive neurons have different morphologic features and different final distributions in the brain.