The in vitro role of tumour necrosis factor-alpha and interleukin-6 in thehypothalamic-pituitary gonadal axis

The adipocyte derived hormone leptin has been implicated as an important nu tritional signal to the reproductive system, but the role of other adipocyt e related cytokines is not clear. Tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 are present in adipose tissue and released into the circulation where plasma levels correlate positively with body mass index a nd body fat mass. These cytokines could play a role in signalling nutrition al status to the hypothalamic-pituitary-gonadal axis. We investigated the e ffects of TNF-alpha and IL-6 on basal and luteinizing hormone releasing hor mone (LHRH) stimulated luteineizing hormone (LH) release from cultured ante rior pituitary cells, harvested from either proestrus female or male Wistar rats. We examined the effects of TNF-alpha and IL-6 on LHRH release from h ypothalamic explants harvested from proestrus female and male rats in vitro . IL-6 significantly suppressed LHRH stimulated LH release from male disper sed pituitaries throughout the dose range, but did not influence basal LH r elease. IL-6 had no effect on basal or LHRH stimulated LH release in disper sed pituitaries from proestrus females. By contrast, TNF-alpha significantl y suppressed LHRH stimulated LH release in dispersed pituitaries from proes trus female rats in a dose responsive manner, but did not influence basal L H release. TNF-alpha had no effect on basal or LHRH stimulated LH release i n dispersed pituitaries from male rats. TNF-alpha and IL-6 had no effect on LHRH release from male hypothalamic explants in vitro. TNF-alpha and IL-6 had no effect on LHRH release from proestrus female hypothalamic explants i n vitro. TNF-alpha and IL-6 have differential effects in dispersed pituitar ies harvested from males and proestrus female rats. TNF-alpha and IL-6 may be important in mediating some of the nutritional effects on the reproducti ve axis by acting at the level of the anterior pituitary rather than the hy pothalamus.