Evaluation of possible determinants and consequences of Leydig cell heterogeneity in man

Leydig cells in the human testis are highly heterogeneous, consisting of variably staining light and dark cells. The basis for this difference is unknown. The present study has assessed whether differing numbers or proportions of dark and light Leydig cells are related: (1) to the pronounced inter-individual variation in testosterone production by isolated Leydig cells, and (2) to differences in structural composition of the testis. Testes (paired weight 6.6-59.48 g) were obtained from 27 men aged 72.9 +/- 9.5 years (range 54-89 years) undergoing orchidectomy as primary treatment for prostatic cancer. Leydig cells were isolated by Percoll-purification and cultured for 20 h under basal and hCG-stimulated conditions. The proportion of light and dark Leydig cells isolated by this method was shown to reflect their proportions in situ, based on the morphometric analysis of fixed testicular tissue from the same men. Leydig cells isolated from all testes produced testosterone in vitro and responded to stimulation by hCG, though the amounts of testosterone produced varied widely between subjects. Because of the latter, samples were grouped into 'low' (n = 9), 'medium' (n = 11) and 'high' (n = 7) groups on the basis of their testosterone production. These groups did not differ in their age, testicular size or gross testicular morphology, though men in the 'high' group tended to have more total Leydig cells per testis. However, there was no overall correlation between testosterone production by isolated Leydig cells and the numbers of light or dark Leydig cells or their ratio or the total number of Leydig cells per testis. The relationship between the volume of light and dark Leydig cells and testicular composition was also assessed. The volume of both types of Leydig cells was strongly correlated (p < 0.001) with the volume of germ cells, but otherwise light and dark Leydig cells correlated positively with different structures. Thus, the volume of light Leydig cells correlated (p < 0.001) with the volume of blood vessels and of peritubular tissue whereas the volume of dark Leydig cells correlated (p < 0.01) with that of the tubular lumen. These differences could indicate differences in regulation and/or function of light and dark Leydig cells. However, the present data do not support the idea that light and dark Leydig cells may differ in their steroidogenic capacity.