Specific depletion of immunoreactive growth hormone-releasing factor by monosodium glutamate in rat median eminence

Abstract

A potent and specific growth hormone-releasing factor (GRF) was recently isolated and characterized from a human islet cell tumour of the pancreas that caused acromegaly^1–3. Antibodies raised against the synthetic replicate of this peptide have allowed the immunohistochemical identification of GRF-producing neurones within the primate central nervous system⁴. Such neurones are found mainly in the arcuate nucleus^4–6 in human and monkey hypothalamus, suggesting that this nucleus is a primary source of GRF. We have further investigated this hypothesis by studying the anatomical organization of GRF neurones in rat hypothalamus, using an antibody raised against the recently characterized rat hypothalamic GRF⁷ in normal animals and in animals neonatally treated with monosodium glutamate (MSG), a treatment which results in the selective destruction of arcuate nucleus neurones^8–10. We present here the results which show that GRF-producing neurones are located mainly in the arcuate nucleus of rats. MSG treatment results in the complete loss of GRF- immunoreactive cell bodies within this nucleus and provokes a selective disappearance of GRF-immunoreactive fibres in the median eminence. These results show that the arcuate nucleus is the origin of the GRF-containing fibres that project to the median eminence and establish the MSG-treated rat as an in vivo model for studying growth hormone secretion in the absence of neurohumoral GRF.