Increased expression of transforming growth factor-α in infantile hypertrophic pyloric stenosis

Abstract

Infantile hypertrophic pyloric stenosis (IHPS) is characterized by hypertrophy of the pyloric muscle. The growth of smooth-muscle cells (SMCs) is regulated by several growth factors. Transforming growth factor-α (TGF-α) is a growth-regulatory peptide found in a wide range of embryonic and adult tissues. It has been recognized that TGF-α has growth-promoting effects in vascular and visceral SMCs. The aim of this study was to investigate whether TGF-α plays a role in the pyloric-muscle hypertrophy in IHPS. Full-thickness pyloric-muscle biopsy specimens were obtained at the time of pyloromyotomy from 10 IHPS patients (age range 24–76 days). Age-matched control material included 10 pyloric-muscle specimens taken at autopsy in patients without evidence of gastrointestinal disease. Indirect immunohistochemistry was performed using the ABC method with anti-TGF-α polyclonal antibody. In-situ hybridization was performed using a digoxigenin-labelled, TGF-α-specific oligonucleotide probe. There was a marked increase in TGF-α immunoreactivity and messenger RNA (mRNA) expression in SMCs in pyloric circular and longitudinal muscle in IHPS specimens compared to controls. The increased expression of TGF-α mRNA together with increased TGF-α immunoreactivity in IHPS suggests increased local synthesis of TGF-α by pyloric SMCs, causing pyloric-muscle hypertrophy.