Ultrastructural studies of the ontogeny of fetal human and procine endocrine pancreas, with special reference to colocalization of the four major islet hormones☆

摘要

Most,ifnotall,endocrinecellsseemcapableofsynthesizingandstoringmorethanonehormone.Suchcellularcolocalizationofhormonescanbedueeithertothepresenceoftwoormorespecificgranuleswithinthecellsortocolocalizationofthehormoneswithinasinglegranule.Thepresentstudywasperformedtoclarifythesubcellularlocalizationofinsulin,glucagon,somatostatin,andpancreaticpolypeptidewithintheendocrinecellsofthehumanandporcinepancreasduringfetaldevelopment,withspecialreferencetopossiblecolocalizationofthehormones.ThetissuespecimenswereprocessedforultrastructuralcytochemistryusingLowicrylasembeddingmedium.Animmunogoldlabelingtechniquewasusedwithtwoparallel,butnotinteracting,antibodychains.Sectionsfromeachspecimenweredoublelabeledindifferentcombinationsgivingacompletecoveringofthefourmajorislethormones.Duringfetallife(50a€“90daysprenatallyinporcinepancreas,14weeksgestationinthehumanpancreas)severalhormonesweredemonstrated,notonlyinthesameendocrinecells,butalsointhesamesecretorygranules(polyhormonalgranules).Costorageofinsulin,glucagon,somatostatin,andpancreaticpolypeptidewasdemonstratedingranulesinpancreaticendocrinefetalcells.Atanearlyfetalstage,theendocrinecellscontainedeitherdense,roundgranulesorpale,heteromorphousgranules.Withincreasingageandmaturationoftheendocrinecells,structuraldifferentiationofthesecretorygranuleswasfoundtobeassociatedwithagradualdisappearanceofthepolyhormonalgranules.Thefirstgenuinemonohormonalcelltoappearintheporcinefetuswasthepancreaticpolypeptidecell(at70daysgestation);itwasfollowedbythesomatostatin-producingendocrinecell.Matureinsulin-andglucagon-producingcellswereonlydemonstratedafterbirth.Thus,intheadultpancreaticendocrinecells,eachspecificendocrinecelltypeproducedonlyoneofthefourclassicalhormones.Thepresentinvestigationdemonstratedthattheendocrinecellsofthefetal,butnottheadult,pancreasareabletosynthesizeallthemajorislethormones,andthatthesepeptidesarecostoredinthesamegranule.Thedataobtainedsupporttheconceptofacommonprecursorstemcellforpancreatichormone-producingcells.