The Paracrine Role Played by Interleukin-1α in the Testis

Abstract

Interleukin-1alpha (IL-1alpha) plays an important role(s) in the regulation of immune and inflammatory responses. The testis is an immunologically privileged organ and the variety of effects exerted by IL-1alpha on this organ have yet to be explored in detail. The aim of the present review is to describe our current view of the paracrine role played by IL-1alpha in testicular physiology. Testicular IL-1alpha is expressed during development, primarily in Sertoli cells, appearing in rats for the first time 20 days after birth. This cytokine is microheterogeneous, consisting of three molecular species with molecular weights of 45, 24 and 17 KDa. The 17 KDa form represents mature IL-1alpha, while the 24-KDa IL-1alpha has been shown by our research group to be an alternately spliced form of the 45-KDa pro-IL-1alpha. IL-1alpha was observed to stimulate the proliferation of immature Sertoli cells with higher efficacy than FSH. IL-1alpha was also found to exert mitogenic effects both on isolated peritubular cells and germ cells. Furthermore, isoforms of IL-1alpha were seen to stimulate basal testosterone production in immature Leydig cells, but not in the corresponding adult cells. This effect involved induction of the steroidogenic acute regulatory (StAR) protein and positively regulation by p38 MAPK. Recently, we have observed positive interactions between IL-1alpha and hormones of the GH/IGF-I system that lead to enhanced androgen production by the Leydig cell. In conclusion, our findings suggest that isoforms of IL-1alpha may serve as paracrine mediators, alone or in concert with other factors, that support proper testicular cell functioning and, thereby, reproduction and fertility.

Opposite regulation of connexin33 and connexin43 by LPS and IL-1α in spermatogenesis

“…This hypothesis is in agreement with the present observations that Cx33 and Cx43 genes were differentially regulated during specific stages of spermatogenesis by phagocytosis and locally produced factors, such as IL-1␣. It is also consistent with our findings in the present study that the increased testicular Cx33 during pubertal development occurs concomitantly with elevated intratesticular IL-1 levels described previously (41).…”

“…22). There is also clear evidence that the effect of residual body phagocytosis could be mediated through IL-1␣ secretion, which reached maximum levels at stages IX and X (40,41). This cytokine is known to exert pleiotropic effects and that among them are mitogenic effects on a wide variety of cells (38), including spermatogonia (20,29).…”

Global proteomics analysis of testis and ovary in adult zebrafish (Danio rerio)

“…ILs, MIF and TNFα are pro-inflammatory cytokines carrying out important roles in inflammation and immunity, as well as in other processes, including reproduction (Wisniewski and Vilcek 2004). Diverse cytokines were shown to modulate steroidogenesis in both testis and ovary (Svechnikov et al 2004; Bornstein et al 2004), and to affect gametogenesis in diverse ways, acting as growth or differentiation factors (Haider 2004; Diemer et al 2003). The rupture of the oocyte from the follicle in many ways resembles an inflammatory reaction, and the IL1 system has been implicated in the oocyte ovulation process (Gerard et al 2004).…”

Peritubular myoid cell‐derived factors and its potential role in the progression of testicular germ cell tumours

“…, 2006). Besides PDGF, Interleukin‐1α is also involved in testicular development as a paracrine factor; this interleukin is first expressed in the rat testis 20 days after birth, mainly by Sertoli cells, and has a mitogenic effect in both PTCs and germ cells (Svechnikov et al. , 2004).…”