Previously, we have shown that two types of luteinizing hormone-releasing h
ormone (LHRH) -like neurons, "early" and"late" cells, were discernible in t
he forebrain of rhesus monkey fetuses by using antiserum. GF-6, which cross
-reacts with several forms of LHRH. The "late" cells that arose from the ol
factory placode of monkey fetuses at embryonic days (E) 32-E36, are bona fi
de LHRH neurons. The "early" cells were found in the forebrain at E32-E34 a
nd settled in the extrahypothalamic area. The molecular form of LHRH in "ea
rly" cells differs from "late" cells, because "early" cells were not immuno
positive with any specific antisera against known forms of LHRH. In this st
udy, we investigated the molecular form of LHRH in the "early" cells in the
nasal regions and brains of 13 monkey fetuses at E35 to E78. In situ hybri
dization studies suggested that both "early" and "late" LHRH cells expresse
d mammalian LHRH mRNA. Furthermore, "early" cells predominantly contain LHR
H1-5-like peptide and its cleavage enzyme, metalloendopeptidase E.C.3.4.24.
15 (EP24.15), which cleaves LHRH at the Tyr(5)-Gly(6) position. This conclu
sion was based on immunocytochemical labeling with various antisera, includ
ing those against LHRH1-5, LHRH4-10, or EP24.15, and on preabsorption tests
. Therefore, in primates, a group of neurons containing mammalian LHRH MRNA
arises at an early embryonic stage before the migration of bona fide LHRH
neurons, and is ultimately distributed in the extrahypothalamic region, The
se extrahypothalamic neurons contain LHRH fragments, rather than fully matu
re mammalian LHRH. The origin and function of these neurons remain to be de
termined. (C) 2001 Wiley-Liss, Inc.