Developmental regulation of Sertoli cell lactate production by hormones and the testicular paracrine factor, PModS.

Testicular peritubular cells produce a paracrine factor termed PModS that mediates mesenchymal-epithelial interactions and modulates Sertoli cell functions essential for the process of spermatogenesis. Sertoli cells produce lactate as a preferred energy metabolite for developing spermatogenic cells. The current study was designed to examine the actions of PModS and hormones on Sertoli cell lactate production at various stages of pubertal development. Sertoli cells were isolated from pre-pubertal (10 day), mid-pubertal (20 day) and late pubertal (35 day) rat testes. Lactate accumulation in the conditioned-medium of cultured Sertoli cells was measured. Basal lactate production increased approximately fivefold during pubertal Sertoli cell development. Therefore, lactate production increases as the Sertoli cell differentiates during pubertal development. The ability of regulatory agents such as FSH or a combination of FSH, insulin, retinol and testosterone (FIRT) to stimulate lactate production decreased during pubertal development as Sertoli cell differentiation increased. Purified PModS stimulated lactate production in Sertoli cell preparations throughout pubertal development. PModS had a greater effect than FSH in stimulating late pubertal Sertoli cell lactate production. PModS in combination with FIRT resulted in an additive stimulation of lactate production suggesting a distinct mechanism of action for PModS. Observations support the proposal that the locally produced paracrine factor PModS mediates mesenchymal-epithelial cell interactions during pubertal development and that these interactions promote Sertoli cell differentiated functions (i.e. lactate production) required for the developing spermatogenic cells.