Increased insulin-like growth factor-I mRNA expression in pyloric muscle in infantile hypertrophic pyloric stenosis

The etiology of infantile hypertrophic pyloric stenosis (IHPS) is unknown. Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that elicits various biological activities (cellular growth, replication, and differentiation) by binding to its receptors. IGF-I has been suggested to play an important role in both gastrointestinal (GI) maturation and smooth-muscle-cell (SMC) hypertrophy. Full-thickness muscle biopsy specimens were obtained from 8 IHPS patients (age range 14-64 days, mean 28.1 days) at pyloromyotomy and from 8 age-matched controls (15-60 days, mean 33.8 days) without GI disease at autopsy. In-situ hybridization was performed using an IGF-I-specific and digoxigenin (DIG)-labeled oligonucleotide probe and visualized by nitroblue tetrazolium staining. In normal controls, IGF-I mRNA expression was absent or weak in both circular and longitudinal smooth-muscle layers of pyloric muscle. In contrast, the pyloric muscle in IHPS patients demonstrated strong IGF-I mRNA expression in the circular smooth-muscle layer and moderate expression in the longitudinal smooth-muscle layer. The increase in IGF-I mRNA in pyloric muscle in IHPS suggests that SMCs are actively synthesizing IGF-I, contributing to the development of pyloric muscle hypertrophy.