Dual nature of Leydig cells of the human testis

Abstract

This review is devoted to the human Leydig cell, and systematizes published and own unpublished results from studies performed during the last decade. Leydig cells are the main cell type in the testis that produce androgens which are important for the development of the male genital organs, secondary sex characteristics and behavior as well as for the processing and maintenance of spermatogenesis. A lot of information accumulated provides evidence that Leydig cells of the human testis and the testis of some other species express or possess immunoreactivities for numerous marker substances characteristic for nerve and neuroendocrine cells. It is shown that human Leydig cells, beside of markers for steroidogenic activity, possess: neuronal markers, synaptic and storage vesicle proteins, neural cytoskeletal proteins, 5-hydroxytryptamine, enzymes involved in the synthesis of catecholamines, neurohormones and/or their receptors, neuropeptides, calcium-binding proteins, cell adhesion molecules, glial cell antigens, components of the nitric oxide/cyclic guanosine monophosphate system, components of the renin/angiotensin system, and numerous growth factors and their receptors. These results provide new evidence for the neuroendocrine nature of Leydig cells. As consequence, two main questions arise: (i) the origin of Leydig cells and (ii) their functional significance as neuroendocrine cells. The presumption that Leydig cells originate from mesenchymal-like cells of the mesonephros is the most common view in the literature. However, no data are provided concerning the origin of the stem cells from which the Leydig cell lineage develops. Mesenchyme comprises the embryonic connective tissue cells that may have mesodermal, ectodermal 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 regulate 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 of blood vessels, thus regulating the blood flow rate and the permeability for hormones and nutritive substances. Also, Leydig cells may regulate the contractile state of peritubular myofibroblasts and myofibroblasts and smooth muscle cells of the tunica albuginea. Similarly, Leydig cells may communicate with Sertoli cells and germ cells of the seminiferous tubules. Leydig cells are a relatively stable, heterogeneous population of cells in the human testis which persists even in cases of impaired spermatogenesis, fibrosis and different 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 independent from the local homeostasis. Biomedical Reviews 1996; 6: 11-41.