Peptides,Vol. 12, pp. 653-663. ©Pergamon Press plc, 1991. Printed in the U,S.A.

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REVIEW

Epidermal Growth Factor and the Nervous System C A R L O S R. P L A T A - S A L A M , ~ d q

School of Life and Health Sciences, University of Delaware, Newark, DE 19716 R e c e i v e d 19 N o v e m b e r 1990

PLATA-SALAM.~I, C. R. Epidermalgrowthfactor and the nervous system. PEPTIDES 12(3) 653-663, 1991.--Various growth factors and their receptors are present in the nervous system. This review focuses on the presence of epidermal growth factor (EGF) and its receptors in the central nervous system (CNS). Evidence indicates that EGF in the CNS is the result of local synthesis, by intrinsic and blood-derived macrophages, glial cells and neurons, and uptake from the peripheral blood through the circumventricular organs and probably also through the blood-brain barrier. Evidence is accumulating suggesting that EGF regulates a variety of CNS functions in a specific manner. EGF influences CNS growth, differentiation and maintenance (actions proposed to promote neural regeneration and cell survival following a variety of insults). EGF also induces neuromodulatory actions, affects the neuroendocrine system, and suppresses food intake and gastric acid secretion. Acute and chronic pathological processes, e.g., various cancers, stimulate the production and release of EGF in various cell systems. Monitoring of EGF by the CNS may participate in several neurological manifestations (e.g., appetite suppression, neuroendocrine alterations) frequently accompanying acute and chronic disease. EGF and transforming growth factor-ct (TGF-et, a factor that binds to the EGF receptor with high affinity and induces the same biological signals as EGF) also may be involved in the promotion of malignancy in the CNS and in the neuropathogenesis of degenerative disorders. Thus evidence is accumulating concerning the neurophysiological or neuropathophysiological significance of EGF in the nervous system. Epidermal growth factor Nervous system Neurotrophic factor Cancer

Neuroendocrine system

A growth factor represents a substance that has the ability to coordinate different aspects of cell growth, proliferation, differentiation, and morpho-functional maintenance by inducing replicative DNA synthesis and cell division (148). Epidermal growth factor (EGF) induces these effects in ectodermal and mesodermal cells. EGF was t'trst detected in 1962 when S. Cohen observed that injection of a mouse submaxillary gland extract accelerated eyelid opening and incisor eruption in newborn mice (30). This extract was purified, the amino acid sequence was determined and various of its biological actions were subsequently demonstrated (31,32). Human EGF and urogastrone (a hormone capable of inhibiting gastric acid secretion) were established to be the same molecule (57,59). Research on the presence and actions of EGF and its receptors on nonneural tissues has been receiving considerable attention [for reviews see (18, 22, 45, 112, 129, 170)]; however, modulation of nervous system functions by EGF has been little studied, but is rapidly expanding. This review summarizes the studies concerning the effects of EGF in the nervous system. This paper also proposes a potential participation of EGF in various neurological manifestations occurring during acute and chronic pathological processes.

Cerebrospinal fluid

Review

6045) (21). The mouse EGF precursor contains 1217 amino acids (mol.wt. of approximately 133,000) and is 66% homologous to the human EGF precursor (9, 56, 156). The mechanism of processing of the preproEGF molecule into EGF is unknown. Human and mouse EGFs share a 70% homology in amino acid structure and present similar locations for the three disulfide bonds (45). GENERALDESCRIPTION EGF is produced by the salivary and Brunner's glands of the gastrointestinal system, kidney, pancreas, thyroid gland, pituitary gland, and the nervous system (23, 45, 112, 129, 170). EGF is found in body biological fluids such as saliva, blood, cerebrospinal fluid (CSF), urine, amniotic fluid, prostatic fluid, pancreatic juice, and breast milk (45, 83, 88, 112). In adult mice, the concentration of EGF in serum is approximately 350400 pg/ml (130) and in plasma ranges from

Epidermal growth factor and the nervous system.

Various growth factors and their receptors are present in the nervous system. This review focuses on the presence of epidermal growth factor (EGF) and...
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