Role of testicular interleukin-1alpha tIL-1alpha in testicular physiology and disease

Abstract

This review focuses on the role of the cytokine interleukin-1alpha (IL-1alpha) in the testis; elaborating upon its importance during the complex process of spermatogenesis while relating this cytokine to some of the pathophysiological states affecting the testis. IL-1alpha, a proinflammatory cytokine, is expressed constitutively by the intact adult rat testis where it acts on germ, Sertoli and Leydig cells to regulate germ cell proliferation and steroidogenesis. The sequence identity of testicular IL-1alpha matches with the one secreted by activated macrophages in systemic immunity. The classical macrophage IL-1alpha is produced as 32 kDa precursor protein which is processed to mature 17 kDa IL-1alpha and a 16 kDa propiece. The rat testicular IL-1alpha, mainly secreted by Sertoli cells, was found to have molecular heterogeneity that can be observed both at the transcriptional and the translational levels. In the rat testis, two transcripts were found to be expressed with 941 bp and 767 bp (that lacks 174 bp) which were translated into 32 kDa and 24 kDa precursor proteins, respectively. The 32 kDa precursor protein is processed to the 17 kDa mature IL-1alpha. Identical transcripts are also shown to be present in cat, dog and pig. Most of the functional role is assigned to the mature 17 kDa IL-1alpha isoform. However, functional analysis of recombinant rat IL-1alpha isoforms showed that there was a clear biopotency difference between these forms in order of 17 kDa IL-1alpha>32proIL-1alpha>24proIL-1alpha. Furthermore, the mature 17 kDa tIL-1alpha has also been implicated in pathologies such as orchitis, relapse of acute lymphoblastic leukemia (ALL) in the testis and infertility disorders in men. Thus, tIL-1alpha may play an important functional role both in coordination of normal testicular physiology as well as in contributing to the disease states in the testis.