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Promotion of Insulin-Like Growth Factor-I Production by Sensory Neuron Stimulation; Molecular Mechanism(s) and Therapeutic Implications

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Abstract:

Insulin-like growth factor-I (IGF-I) plays various important roles in cellular proliferation, differentiation, survival and functions of the cell, thereby contributing to the maintenance of tissue integrity. Although it is well known that growth hormone (GH) increases serum IGF-I levels by stimulating the hepatic production, little is known about the mechanism by which local production of IGF-I in individual tissues is regulated. Stimulation of sensory neurons by capsaicin increases tissue levels of IGF-I and IGF-I mRNA in various organs via increased calcitonin gene-related peptide (CGRP) release in mice. This sensory neuronmediated IGF-I production contributes to reducing reperfusion-induced liver injury through prevention of apoptosis in mice. Isoflavone, a phytoestrogen, increases CGRP production by increasing its transcription in sensory neurons. Administration of capsaicin and isoflavone increases IGF-I production in hair follicles, thereby promoting hair growth in mice and in volunteers with alopecia. Topical application of capsaicin increases dermal levels of IGF-I by stimulating sensory neurons in mice and increases facial skin elasticity in humans. Plasma and tissue levels of CGRP and IGF-I in spontaneously hypertensive rats (SHR) are lower than those in normotensive Wistar Kyoto rats (WKY), contributing to the development of hypertension, heart failure and insulin resistance in SHR. Administration of capsaicin increases CGRP and IGF-I levels in plasma, kidneys and the heart in SHR to WKY levels, and normalizes mean arterial blood pressure in SHR. Since administration of GH or IGF-I has some deleterious effects, pharmacological stimulation of sensory neurons leading to increased tissue IGF-I levels might be a novel therapeutic strategy for various pathologic conditions.

Keywords: Insulin-like growth factor-I; apoptosis; calcitonin gene-related peptide; nitric oxide; prostaglandins; sensory neurons; tumor necrosis factor

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708786848604

Affiliations: Department of Translational Medical Science Research, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467- 8601, Japan.

Publication date: December 1, 2008

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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