Ultrastructure of cell contacts of fetal and adult Leydig cells in the rat: a systematic study from birth to senium.

Differentiation, development, and function of Leydig cells in the testis are regulated also by macrophages, vascular endothelial cells, and peritubular cells in the testis. The aim of the present study was to investigate the possible morphological substrates for communication between these cells. The cell contacts between adjacent Leydig cells, and between Leydig cells and other interstitial cells were studied electron microscopically in the rat testis of various age groups from birth to senium. Intercellular bridges with continuous cytoplasm were observed between fetal Leydig cells (FLCs) in the early postnatal period. Gap junctions were present in nearly every age group. A structural diversity as well as an increased occurrence of gap junctions with the maturity of the Leydig cells was noted. Coated pits were observed initially on pnd 30. From pnd 50 onwards, macrophages and Leydig cells were attached very closely to each other, when the cell processes of Leydig cells protruded either into the coated pits or into the deep invaginations of macrophages. To conclude, this is the first report on the presence of intercellular bridges between FLCs suggesting a possible functional synchronization of interconnected Leydig cells. The cell contacts observed here are possibly required for a precise communication between the Leydig cells and other interstitial cells.

Cell biology of Leydig cells in the testis.

This article reviews results on differentiation, structure, and regulation of Leydig cells in the testes of rodents and men. Two different populations-fetal and adult Leydig cells-can be recognized in rodents. The cells in these two populations are different in ultrastructure, life span, capacity for androgen synthesis, and mechanisms of regulation. A brief survey on the origin, ontogenesis, characterization of precursors, ultrastructure, and functional markers of fetal and adult Leydig cells is presented, followed by an analysis of genes in Leydig cells and the role of luteinizing hormone and its receptor, steroidogenic acute regulatory protein, hydroxysteroid dehydrogenases, androgen and its receptor, anti-Müllerian hormone, estrogens, and thyroid hormones. Various growth factors modulate Leydig cell differentiation, regeneration, and steroidogenic capacity, for example, interleukin 1alpha, transforming growth factor beta, inhibin, insulin-like growth factors I and II, vascular endothelial growth factor, and relaxin-like growth factor. Retinol and retinoic acid increase basal testosterone secretion in adult Leydig cells, but decrease it in fetal Leydig cells. Resident macrophages in the interstitial tissue of the testis are important for differentiation and function of Leydig cells. Apoptosis of Leydig cells is involved in the regulation of Leydig cell number and can be induced by cytotoxins. Characteristics of aging Leydig cells in rodents seem to be species specific. 11beta-hydroxysteroid dehydrogenase protects testosterone synthesis in the Leydig cells of stressed rats. Last, the following aspects of human Leydig cells are briefly described: origin, differentiation, triphasic development, aging changes, pathological changes, and gene mutations leading to infertility.

Trends of reproductive hormones in male rats during psychosocial stress: role of glucocorticoid metabolism in behavioral dominance.

Stress in socially subordinate male rats, associated with aggressive attacks by dominant males, was studied in a group-housing context called the visible burrow system (VBS). It has been established that subordinate males have reduced serum testosterone (T) and higher corticosterone (CORT) relative to dominant and singly housed control males. The relationship of the decreased circulating T levels in subordinate males to changes in serum LH concentrations has not been evaluated previously. Since decreases in LH during stress may cause reductions in Leydig cell steroidogenic activity, the present study defined the temporal profiles of serum LH, T, and CORT in dominant and subordinate males on Days 4, 7, and 14 of a 14-day housing period in the VBS. The same parameters were followed in serum samples from single-housed control males. Leydig cells express glucocorticoid receptors and may also be targeted for direct inhibition of steroidogenesis by glucocorticoid. We hypothesize that Leydig cells are protected from inhibition by CORT at basal concentrations through oxidative inactivation of glucocorticoid by 11beta-hydroxysteroid dehydrogenase (11betaHSD). However, Leydig cell steroidogenesis is inhibited when 11betaHSD metabolizing capacity is exceeded. Therefore, 11betaHSD enzyme activity levels were measured in Leydig cells of VBS-housed males at the same time points. Significant increases in LH and T relative to control were observed in the dominant animals on Day 4, which were associated with the overt establishment of behavioral dominance as evidenced by victorious agonistic encounters. Serum LH and T were lower in subordinate males on Day 7, but T alone was lower on Day 14, suggesting that lowered LH secretion in subordinates may gradually be reversed by declines in androgen-negative feedback. Serum CORT levels were higher in subordinate males compared to control at all three time points. In contrast, oxidative 11betaHSD activity in Leydig cells of dominant males was higher relative to control and unchanged in subordinates. These results suggest the following: 1) failure of Leydig cells of subordinate males to compensate for increased glucocorticoid action during stress, by increasing 11betaHSD oxidative activity, potentiates stress-mediated reductions in T secretion; and 2) an inhibition of the reproductive axis in subordinate males at the level of the pituitary.