Inflammatory mediators are the major determinant of delayed puberty associated with intestinal inflammation

Abstract

Delayed puberty occurs in 20-30% of adolescents with IBD and is thought to result primarily from anorexia and reduced energy intake induced by inflammatory cytokines. However, cytokines may also directly inhibit the hypothalamic-pituitary-gonadal axis. The aim of this study was to determine in the rat TNBS-colitis model if nutritional deficit or systemic inflammation has the major effect. Methods. Colitis was induced and maintained in prepubertal mile Wistar rats (age 32 days) by intrarectal administration of TNBS in ethanol. One group of healthy animals were pair-fed (PF) to match the food intake of the colitic group and a second control group allowed free access to food. Food intake and body weight was measured daily and onset of puberty (complete separation of prepuce from glans) noted. Animals were sacrificed at 48 days and sex organs removed for weighing. Inflammation was assessed by measurement of intestinal myelnperoxidase (MPO). Results: TNBS induced distal colitis with increased MPO concentrations (colitis, 27 -+ 8.3; controls, 3.7 +_ 0.9; PF, 1.6 -+ 0.6 mU/g) and hypophagia (mean total 16 day intake, 257g; controls, 417g). By definition food intake of PF and colitic groups was equal. Despite the same degree of malnutrition in colitic and PF groups, colitic animals showed delay in puberty (table). There was no evidence of onset of puberty in 40% of the oolitic group but all controls and PF had entered puberty.