The genes encoding nerve growth factor and its receptor are expressed in the developing female rat hypothalamus

Nerve growth factor (NGF), its messenger RNA (mRNA) and its receptor protein and mRNA are found in several brain regions. Little attention has been given to the possibility that the hypothalamus, which controls the endocrine system, may produce NGF and/or express NGF receptors. This would indicate the existence in this brain area of neuronal populations which are either target for NGF-responsive cells or sensitive to NGF, respectively. Blot hybridization of polyadenylated (poly(A)⁺) RNA to a mouse NGF cRNA probe revealed the presence of NGF mRNA in both the suprachiasmatic region (henceforth, called preoptic area [POA]) and medial basal hypothalamus (MBH) of developing female rats. The mRNA was already detectable on fetal day 18 and reached maximal levels around postnatal day 3 (MBH) and 12 (POA), declining thereafter. This pattern was temporally different than that of areas known to produce NGF, i.e., the neocortex (Cc) and hippocampus (Hc). In agreement with previous reports, NGF mRNA levels in these areas were negligible before birth, became maximal between the second and third week of postnatal life and decreased moderately thereafter. The concentration of NGF protein, measured by a two-site enzyme immunoassay, was 3 times higher in the POA than in the MBH at an infantile age (day 12), increasing 2-fold in the POA of juvenile animals (day 28) but not in the MBH. This developmental pattern was similar to that seen in the Hc, though the NGF concentrations were significantly lower in the POA. Although NGF levels did not appear to change in the MBH during development, the median eminence of juvenile rats microdissected from the rest of the hypothalamus had a NGF concentration 3 times that of the MBH as a whole. The developmental pattern of NGF receptor (NGFr) mRNA was studied by RNA blot hybridization to a rat cRNA probe. NGFr mRNA was detected throughout prepubertal development in both the POA and MBH, the levels being higher in the POA than in the MBH, at all ages examined. In both regions, the level of expression varied little during the postnatal period studied. This was in contrast to the cerebellum (Cb), Hc and Cc in which the highest NGFr mRNA levels were found during late fetal development and first week of postnatal life, becoming minimal thereafter. Biochemical characterization of the receptor by cross-linking ¹²⁵I-NGF to cell membranes, followed by immunoprecipitation, sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography, revealed the presence in both the POA and MBH of an ∼90 kDa species which corresponds to the expected size of the receptor cross-linked to NGF and that was identical in size to the NGF receptor species detected in the neonatal cerebellum, a region rich in NGF receptors. The results demonstrate the ability of the developing female hypothalamus to express NGF and its receptor. The transient elevation of NGF mRNA levels during the neonatal-infantile period suggests the existence of hypothalamic cells which are targets for NGF-sensitive neurons located in the hypothalamus itself and/or elsewhere in the brain. The sustained expression of NGFr mRNA during the first 5 weeks of postnatal life indicate that the prepubertal hypothalamus also contains NGF-responsive cells.