Tyrosine hydroxylase (TH) - the specific marker of the catecholamine synthesizing cells, has been detected in the pancreatic endocrine, acinar and ductal cells in some mammals. In the developing mouse pancreas, TH+ cells are often contained glucagon and shared some features that are characteristics for differentiated endocrine cells. As it was shown in experimental studies on mice, a non-neural catecholaminergic pathway appears to modulate pancreatic endocrine precursor and insulin producing cell neogenesis. Our aim was to evaluate whether TH+ cells are present in the developing human pancreas. We have analyzed pancreatic autopsies from 34 human fetuses (10-37 gestational weeks (g.w.)) using double immunofluorescent labeling with antibodies to TH and either insulin or glucagon. Rare TH+ cells were found in the pancreas of all fetuses from 10th to 21th g.w., which were not detected later in development. At early stages (10-12 g.w.), such cells were located among the epithelial cells of primitive ducts, often in close proximity to the endocrine cell clusters, or were associated with the TH+ nerve bundles. In the pancreas of fetuses from 14th to 21th g.w., TH+ cells were observed in the nerve bundles, nerve ganglia and in the neuro-inular complexes type 1 (endocrine cells integrated with the neurons and nerve fibers). Some of the TH+ cells simultaneously contained glucagon. However, the majority of the TH+ cells were negative for insulin or glucagon. Thus, we first detected TH+ cells in the human fetal pancreas. These cells may be differentiating endocrine cells, because some of the TH+ cells were located in the ductal epithelium and rarely contained glucagon. Similarly with mice, non-neural catecholamines may be involved in the endocrine cells differentiation during human pancreas development.
Y. Krivova: None. A. Proshchina: None. D. Otlyga: None. O. Leonova: None. V. Popenko: None. V. Barabanov: None. S. Saveliev: None.
Russian Foundation for Basic Research (18-015-00146)