Involvement of intratesticular IL-1 system in the regulation of Sertoli cell functions.

The Interleukin-1 (IL-1) system has been suggested to be involved in the cell-cell cross talk within the testis. To investigate the testicular autocrine, paracrine and endocrine factors involved in the regulation of Sertoli cell functions, we have examined the capacity of Sertoli cell cultures, from immature mice, to produce IL-1alpha, IL-1beta and IL-1 receptor antagonist (IL-1ra) under in vitro cultures and in the presence of testicular physiological and pathological factors. Our investigation revealed that Sertoli cells produce large amounts of IL-1alpha, IL-1ra but not IL-1beta under basal culture conditions, as examined by ELISA and immunohistochemical staining. Liposaccharides (LPS), as well as IL-1alpha and IL-1beta were found to stimulate IL-1alpha and IL-1ra, but not IL-1beta production, in Sertoli cells from immature mice. Maximum concentration of IL-1alpha and of IL-1ra was observed after 2 and 8 h after the stimulation, respectively. The addition of IL-1ra to Sertoli cells did not alter their capacity to constitutively produce IL-1alpha. However, the stimulatory effects of recombinant IL-1alpha on IL-1alpha production by Sertoli cells were reversed by the concomitant addition of recombinant IL-1ra. FSH is capable to induce IL-1ra production in Sertoli cells in a dose-dependent manner but not IL-1alpha or IL-1beta. As expected, Sertoli cell cultures were also shown to constitutively secrete transferrin. Stimulation of these cultures with IL-1alpha, IL-1beta significantly increased their capacity to secrete transferrin. Addition of IL-1ra to unstimulated Sertoli cell cultures did not affect their capacity to secrete transferrin. Stimulation of Sertoli cell cultures with a combination of both IL-1alpha and FSH or IL-1beta and FSH showed additive effect between IL-1 and FSH in their capacity to induce transferrin secretion by these cells. However, stimulation of Sertoli cells with a combination of both IL-1ra and FSH did not affect their capacity to secrete transferrin as compared with FSH-stimulated cultures. Our results with Sertoli cells, in addition to previous data on Lydig cell and germ cells, may suggest the involvement of the IL-1 system in testicular paracrine/autocrine regulation, which could be involved in the regulation of spermatogenesis and spermiogenesis processes and male fertility.