LOCAL-REGULATION OF MACROPHAGE SUBSETS IN THE ADULT-RAT TESTIS - EXAMINATION OF THE ROLES OF THE SEMINIFEROUS TUBULES, TESTOSTERONE, AND MACROPHAGE-MIGRATION INHIBITORY FACTOR

In the adult rat testis, macrophages belong to one of two subsets diff erentiated by expression or lack of expression of the resident macroph age surface antigen recognized by monoclonal antibody ED2. Local regul ation of the testicular macrophage subsets was investigated in normal and 4-wk experimentally clyptorchid adult rats with and without s.c. t estosterone implants (T-implants). Macrophage subsets ED2(+) (resident -type) and ED2(-) (monocyte-like) were identified immunohistochemicall y and counted in perfusion-fixed frozen testis sections. Depletion of the spermatogenic cells by cryptorchidism had no effect on testicular macrophage numbers. Inhibition of Leydig cell and seminiferous tubule function by low-dose (3 cm) T-implants caused a 40% reduction in ED2() resident macrophages in both scrotal and abdominal testes. High-dose (24 cm) T-implants, which inhibit Leydig cell function while maintain ing normal seminiferous tubule function, also reduced the number of re sident macrophages by approximately 40%, although this reduction was a t least partially prevented in the abdominal testes. In the scrotal te stis only, the ED2(-) monocyte/macrophage subset was significantly red uced in number by low-dose, but not high-dose, T-implants. The concent ration of the Leydig cell-secreted cytokine macrophage-migration inhib itory factor (MIF) in testicular fluid was reduced by cryptorchidism, but not by the T-implants. When data from all experimental groups were combined, ED2(+) resident macrophage numbers showed a significant pos itive correlation with parameters of Leydig cell function (serum LH an d testicular testosterone levels) but a negative correlation with MIF levels. This study indicates that Leydig cells regulate testicular mac rophage numbers directly, rather than via an effect upon the seminifer ous epithelium, in the adult rat testis. The data also suggest that te stosterone and MIF play only a minor role, if any, in this regulation.