ABSTRACT. It has been reported that when the rat fetus is treated with streptozotocin (STZ) in vivo, islet B cells are destroyed but later recover. To investigate the process of the recovery of B cells after in vitro treatment of the fetal pancreas with STZ and the role of epidermal growth factor (EGF) in the recovery of B cells, we measured the level of insulin released from the cultured fetal pancreas and examined it histologically. As a result, we immunohistologically confirmed the regeneration of B cells in the pancreas that had been cultured for 48 hr after destruction of islet B cells by STZ treatment. An immunohistologic study using proliferating cell nuclear antigen (PCNA) showed that without the addition of EGF, the cell division index was significantly higher in the STZ-treated group (STZ group) than in the untreated group (intact group), whereas with the addition of EGF, the cell division index increased in both groups, but EGF did not have a significant cell division-promoting effect on the pancreas in the STZ group. The addition of EGF caused a significant decrease in the concentration of insulin in culture medium in both groups. These results indicate that EGF has a cell growth-promoting effect on intact fetal pancreas in vitro but has the effect of inhibiting the release of insulin, and thus suggest that EGF does not trigger the regeneration of islet B cells. KEY WORDS: epidermal growth factor (EGF), fetal islet B cell, insulin, proliferating cell nuclear antigen (PCNA), streptozotocin (STZ).J. Vet. Med. Sci. 64(2): 101-105, 2002 Epidermal growth factor (EGF) is a polypeptide of molecular weight 6,045 originally extracted from the submaxillary glands of mice and accelerates eyelid opening and incisor eruption in newborn mice [5]. EGF has also been reported to function in accelerating the growth of the gastrointestinal mucosal epithelium, inhibiting the secretion of gastric acid, and protecting the gastric mucosa [6,10].EGF has been shown to affect the growth and differentiation of cultured cells derived from various organs [3], and reportedly has in vivo and in vitro growth-accelerating effects on the pancreas [4]. However, these in vitro studies used the isolated exocrine part or pancreatic islets, and not intact pancreases in organ culture.EGF receptors are present in various cells [3], and their presence in the pancreas has also been confirmed [7,15,19]. From the observation that EGF occurs in pancreatic tissue and pancreatic juice [12][13][14], it is postulated that EGF has some effect on the pancreas itself.Streptozotocin (STZ) is an experimental diabetogenic agent that causes diabetes mellitus by specifically destroying islet B cells [23]. Its toxic action on islet B cells is irreversible. However, it has been reported that perinatal rats subjected to STZ treatment reversibly recover from STZinduced diabetes mellitus [2,22]. It has also been reported that the direct administration of STZ to the rat fetus immediately decreases the total mass of the islet B cells, which is markedly restored...