Stimulatory effect of interleukin 1b (IL1b) on testicular cyclooxygenase 2 (COX2) expression: possible relevance to male fertility

FRUNGIERI MB, MATZKIN ME, GONZALEZ-CALVAR SI, MAYERHOFER A, CALANDRA RS.

Toronto, Canadá

Congreso; Annual Meeting of the Endocrine Society; 2007

Endocrine Society

We have previously described: a) a significant increment in the number of testicular macrophages (MAC) containing IL1b (1) and induction of interstitial COX2 expression (key enzyme in the biosynthesis of prostaglandins, PGs) (2) in testicular biopsies from infertile men, b) the existence of COX2 expression in testes of adult Syrian hamsters exposed to a long-day photoperiod (LD, 14h light: 10h dark) and the absence of COX2 expression in testes of adult hamsters exposed to a short-day photoperiod (SD, 6h light: 18h dark), rats, mice, monkeys, and pigs (3), c) 15d-PGJ2 induction of human testicular fibrosis (1,4), and d) regulation of hamster testicular testosterone production by PGF2a and PGD2 (3,5).The aim of this study was to investigate the expression of IL1b, its functional receptor RI, its scavenger receptor RII, and the receptor antagonist Ra, in human testicular biopsies and hamster testes. Since the active adult hamster is a readily available model to study the testicular induction of COX2, we have also investigated the effect of IL1b on COX2 expression in purified hamster Leydig cells. Expression of IL1b and its functional receptor RI was detected by RT-PCR in CD68-immunoreactive MAC and COX2-positive Leydig cells isolated by laser microdissection from human biopsies of patients with germ arrest (GA) and Sertoli cell only (SCO) syndromes. Expression of IL1b, the functional receptor RI, the scavenger receptor RII and the antagonist receptor Ra was also found in LD-hamster Leydig cells isolated by Percoll density gradient. In contrast, COX2-negative Leydig cells from SD-hamsters did not expressed IL1b. Furthermore, IL1b significantly increased COX2 expression (RT-PCR, fold change units, basal: 1+0.2; IL1b 50 ng/ml: 8.1+0.7, P<0.05) in LD-hamster Leydig cells. Thus, the IL1b system is present in testicular macrophages and Leydig cells. In addition, induction of COX2 expression by IL1b has been described in hamster Leydig cells. Since normal human testes with few IL1b-immunoreactive MAC do not express COX2, but pathological human testes with an increased number of IL1b-positive MAC show expression of IL1b, its functional receptor RI and COX2 in Leydig cells, we suggest that IL1b might play a key role in the regulation of testicular COX2 expression and PGs production in male infertility. (1) Frungieri MB et al., 2002; Fertil Steril 78:298 (2) Frungieri MB et al., PNAS 2002; USA 99:15072  (3) Frungieri MB et al., Endocrinology 2006; 147:4476 (4) Frungieri MB et al., Cell Signal 2005; 17:525 (5) Schell C, Frungieri MB et al., Fertil Steril 2007, in press Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT); Universidad de Buenos Aires (UBACYT); Fundacion Antorchas; Deutscher Akademischer Austausch dienst (DAAD).