Polyhormonal aspect of the endocrine cells of the human fetal pancreas

Histological studies were performed on 30 pancreases obtained from normal h uman fetuses aged between the 9th and 38th week. For immunocytochemistry, t he avidin-biotin-peroxidase method was used to identify and colocalise insu lin, glucagon, somatostatin, pancreatic polypeptide and proliferating cell nuclear antigen. In the 9th week, cells containing all investigated peptide s were present. During the fetal period, two populations of endocrine cells have been distinguished, Langerhans islets and freely dispersed cells. The free cells were polyhormonal, containing insulin, glucagon, somatostatin a nd pancreatic polypeptide. and were localised in the walls of pancreatic du cts throughout the whole gland. During the development of the islets we hav e observed four stages: (1) the scattered polyhormonal cell stage (9th-10th week), (2) the immature polyhormonal islet stage (11th-15th week), (3) the insulin monohormonal core islet stage (16th-29th week), in which zonular a nd mantle islets are observed, and (4) the polymorphic islet stage (from th e 30th week onwards), which is characterised by the presence of monohormona l cells expressing glucagon or somatostatin. Bigeminal and polar islets als o appeared during this last stage. The islets consisted of an insulin core surrounded by a thick (in the part developing from the dorsal primordium) o r thin rim (part of the pancreas concerned with the ventral primordium) of intermingled mono- or dihormonal glucagon-positive or somatostatin-positive cells. The most externally located polyhormonal cells exhibited a reaction for glucagon, somatostatin and pancreatic polypeptide. Apart from the abov e-mentioned types of islets, all arrangements observed in earlier stages we re present. Proliferating cell nuclear antigen-positive cells (single in th e large islets and more numerous in the smaller ones) were predominantly ob served in the outermost layer. Taken together our data indicate that, durin g the human prenatal development of the islet, endocrine cells are able to synthesise several different hormones. Maturation of these cells involved o r depended on a change from a polyhormonal to a monohormonal state and is c oncerned with decreasing proliferative capacity. This supports the concept of a common precursor stem cell for the hormone-producing cells of the feta l human pancreas.