Dual nature of Leydig cells of the human testis
Michail S. Davidoff, Ralf Middendorff, and Adolf F. Holstein ( Germany )
This revie w is devoted to the human Ley dig cell, and systematizes published and own unpublished results from stud- ies performed during the last decade. Ley dig cells are the main cell type in the testis that produce androgens which are impor- tant for the development of the male genital organs, second- ary sex characteristics and behavior as well as for the process- ing and maintenance ofspertnatogenesis. A lot of information accumulated provides evidence that Ley dig cells of the human testis and the testis of some other species express or possess immunoreactivities for numerous marker substances charac- teristic for nerve andneuroendocrine cells. It is shown that hu-
man Leydig cells, beside of markers for steroidogenic activ- ity, possess: neuronal markers, synoptic and storage vesicle proteins, neural cytoskeletal proteins, 5-hydroxytryptamine, enzymes involved in the synthesis ofcatecholatnines, neurohor-mones and/or their receptors, neuropeptides, calcium-binding proteins, cell adhesion molecules, glial cell antigens, compo- nents of the nitric oxide/cyclic guanosine monophosphate sys- tem, components of the renin/angiotensin system, and numer- ous growth factors and their receptors. These results provide new evidence for the neuroendocrine nature of Leydig cells. As consequence, t\vo main questions arise: (i) the origin of Leydig cells and (ii) their functional significance as neuroen- docrine cells. The presumption that Leydig cells originate from mesenchymal-like cells of the mesonephros is the most com- mon view in the literature. However, no data are provided con-cerning the origin of thestem cells from which the Leydig cell lineage develops. Mesenchyme comprises the embryonic con- nective tissue cells that may have mesodermal, ectoderrnal and neuroectodermal (neural crest) origin. In this relation and based on the recently established neuroendocrine feature, we speculate that Leydig stem cells may detach from unknown regions of the neural crest and migrate to the mesonephric and gonadal anlage at early stages of development. The functional significance of Leydig cells as neuroendocrine cells is also illustrated on the basis of the nitric oxide/cyclic guanosine monophosphate system. Accordingly, Leydig cells may regu- late their steroidogenic activity by an intracrine or autocrine fashion. Furthermore, they are probably able to synchronize the activity of the cells in a Leydig cell cluster by a paracrine way. Leydig cells may influence the contractile activity of the smooth muscle cells ofbloodvessels, thus regulating the blood flow rate and the permeability for hormones and nutritive sub- stances. Also, Leydig cells may regulate the contractile state ofperitubular myofibroblasts and myofibroblasts and smooth muscle cells of the tunica albuginea. Similarly, Leydig cells may communicate with Sertoli cells and germ cells of the se- miniferous tubules. Leydig cells are a relatively stable, hetero- geneous population of cells in the human testis which persists even in cases of impaired spermatogenesis,fibrosis and differ- ent pathological changes of the testis. This fact suggests that Leydig cells survive under unusual conditions due to precise regulatory systems which make them to a larger extent inde-pendent from the local homeostasis.
Biomed Rev 1996; 6: 11-41.