Neurotrophic factors in the testis

Neurotrophic factors, interacting with neurons to affect their growth, are a subset of the polypeptide growth factors. There is increasing evidence for a broader physiological role of these factors which includes effects on a variety of nonneuronal tissues. Among the cell systems, where neurotrophic factors have been hypothesized to exert local nonneurotrophic activities, the testis is of particular interest. This organ represents a complex biological unit which requires the concerted action of very diverse cell types interacting with each other in order to ensure correct spermatogenesis. As signaling molecules that may be involved in these intercellular communication events, various neurotrophic factors have attained considerable scientific attention. This article intends to summarize the presently available data on the distribution and possible local activities of neurotrophic factors and their receptors in testicular cells and provides further information on local expression sites of some of these factors in the human testis.Biomedical Reviews 1999; 10: 25-30

The C-type natriuretic peptide system in the testis: a physiological role of neuroactive factors in Leydig cells

Androgen production is the primary function of testicular Leydig cells. Recently, Leydig cells of the human testis have been shown to possess, along with well developed smooth endoplasmic reticulum, cytoplasmic vesicles and storage granules similar to those found in neuroendocrine and nerve cells. Moreover, a series of nerve cell-specific substances has been detected in Leydig cells. However, little is known about the physiological role of these molecules in testicular function.Biomedical Reviews 1997; 8: 111-117

Dual nature of Leydig cells of the human testis

This review is devoted to the human Leydig cell, and systematizes published and own unpublished results from studies performed during the last decade.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

Progenitor cells of the testosterone-producing Leydig cells revealed

The cells responsible for production of the male sex hormone testosterone, the Leydig cells of the testis, are post-mitotic cells with neuroendocrine characteristics. Their origin during ontogeny and regeneration processes is still a matter of debate. Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells. Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin. Using an in vivo model to induce and monitor the synchronized generation of a completely new Leydig cell population in adult rats, we demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells which, in addition, rapidly acquire neuronal and glial properties. These findings, shown to be representative also for ontogenetic Leydig cell formation and for the human testis, provide further evidence that cellular components of blood vessels can act as progenitor cells for organogenesis and repair

Age Related Differences in Responsiveness to Sildenafil and Tamsulosin are due to Myogenic Smooth Muscle Tone in the Human Prostate

Lower urinary tract symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH) are highly prevalent in older men, having a profound impact on patient quality of life. Current therapeutics for BPH/LUTS target neurogenic smooth muscle tone, but response is unpredictable and many patients fail to respond. Spontaneous myogenic tone is another component of smooth muscle contractility that is uncharacterized in human prostate. To better understand and improve the predictability of patient response, we defined myogenic contractility using human prostate specimens and examined the effect of existing therapeutics. We show that myogenic activity is present in the human prostate with the frequency of contractions in transition zone (TZ) specimens from BPH diagnosed patients approximately 160% greater than matched controls. α1-adrenoreceptor antagonists (Tamsulosin) and PDE5 inhibitors (Sildenafil) both significantly reduced myogenic contractile parameters, including frequency, with notable interpatient variability. Tamsulosin was more effective in older patients (R2 = 0.36, p < 0.01) and men with larger prostate volumes (R2 = 0.41, p < 0.05), while Sildenafil was more effective in younger men (R2 = 0.45, p < 0.05). As myogenic tone is significantly increased in BPH, therapeutics targeting this mechanism used with reference to patient characteristics could improve clinical outcomes and better predict patient response