Leydig cells in the testis of the rat : heterogeneity, development and similarities with macrophages

Leydig cells are present in the interstitium of the testis and are responsible for the steroid production of the testis. This production is regulated by the pituitary hormone LH and there are indications that it is also under the influence of local factors. Heterogeneity of cell populations has been reported for a variety of cell types. Factors which can account for this heterogeneity are e.g. differences in the stage of differentiation and differences in localization, whereas in other cases the heterogeneity appeared to be related to "intrinsic" properties of the cells. There are indications that the population of Leydig cells present in the testis is heterogeneous too. Several authors have isolated subpopulations of Leydig cells differing in steroidogenic activities. Besides Leydig cells the interstitium also contains macrophages, fibroblasts, myoid cells, endothelial cells and mesenchymal cells. The macrophages are found closely associated with Leydig cells and have some properties in common with Leydig cells. This may give rise to a heterogeneity within the population of ''Leydig cells". The differentiation of Leydig cells in the rat shows a biphasic pattern. Two generations of Leydig cells can be discerned: the foetal generation and the adult generation. The adult population of Leydig cells undergoes many changes during sexual development. If this occurs asynchronously, this may result in a heterogeneous population of Leydig cells during this period. Little is known about the turnover of Leydig cells after maturation and it is not clear, therefore, whether and to which extent differentiation of Leydig cells contribute to the heterogeneity of the Leydig cells present in testes from mature rats. The precise nature of the precursor cell which gives rise to the adult population of Leydig cells has not been elucidated yet. Mesenchymal cells, fibroblasts, endothelial cells and also macrophages have been mentioned as possible precursor cells. The work described in this thesis concerns: 1. the heterogeneity of Leydig cells 2. the (dis)similarities between Leydig cells and macrophages in the testis 3. the development of Leydig cells The heterogeneity of Leydig cells obtained from mature rats and the effect of the isolation procedure on the heterogeneity of the resulting cell preparation was evaluated by comparing different isolation procedures (Chapter II.1.). Attempts to separate Leydig cells into different subpopulations are described in Chapter II.2. Properties of testicular macrophages and Leydig cells were compared using markers specific for Leydig cells or macrophages (Chapter III)· Administration of a chemical compound Ethylene Dimethane Sulfonate (EDS) causes a selective depletion of Leydig cells followed by a regeneration of Leydig cells. This process of regeneration and the role of the gonadotrophic hormones is described in Chapter IV. The change of the cellular composition of the interstitial tissue as a whole and the changes in properties of Leydig cells in the interstitium during sexual maturation have been described in Chapter V. In Chapter VI the results are discussed with respect to heterogeneity, origin and development of Leydig cells and a possible role of the Leydig cells in immunosuppression.