Endotoxin-induced inflammation disturbs melatonin secretion in ewe

Abstract

ObjectiveThe study examined the effect of intravenous administration of bacterial endotoxin—lipopolysaccharide (LPS) —on the nocturnal secretion of melatonin and on the expression of enzymes of the melatonin biosynthetic pathway in the pineal gland of ewes, taking into account two different photoperiodic conditions: short-night (SN; n = 12) and long-night (LN; n = 12).MethodsIn both experiments, animals (n = 12) were randomly divided into two groups: control (n = 6) and LPS-treated (n = 6) one. Two hours after sunset, animals received an injection of LPS or saline. Blood samples were collected starting one hour after sunset and continuing for 3 hours after the treatment. The ewes were euthanized 3 hours after LPS/saline treatment. The concentration of hormones in plasma was assayed by radioimmunoassay. In the pineal gland, the content of serotonin and its metabolite was determined by HPLC; whereas the expression of examined genes and protein was assayed using real-time polymerase chain reaction and Western Blot, respectively.ResultsEndotoxin administration lowered (p<0.05) levels of circulating melatonin in animals from LN photoperiod only during the first hour after treatment, while in ewes from SN photoperiod only in the third hour after the injection. Inflammation more substantially suppressed biosynthesis of melatonin in ewes from SN photoperiod, which were also characterised by lower (p<0.05) cortisol concentrations after LPS treatment compared with animals from LN photoperiod. In the pineal gland of ewes subjected to SN photoperiod, LPS reduced (p<0.05) serotonin content and the expression of melatonin biosynthetic pathway enzymes, such as tryptophan hydroxylase and arylalkylamine-N-acetyltransferase. Pineal activity may be disturbed by circulating LPS and proinflammatory cytokines because the expression of mRNAs encoding their corresponding receptors was determined in this gland.ConclusionThe present study showed that peripheral inflammation reduces the secretion of melatonin, but this effect may be influenced by the photoperiod.

The effect of inflammation on the synthesis of luteinizing hormone and gonadotropin-releasing hormone receptor expression in thepars tuberalisof ewe during different photoperiodic conditions

“…Moreover, it was found that LPS-induced inflammation decrease the circulating level of melatonin in ewes in LD but not in SD period. These results are consistent with previous studies on ewes (Reiter et al 2009;Herman et al 2016aHerman et al , 2017Król et al 2016). It was demonstrated that inflammatory-dependent decrease in the melatonin release during LD photoperiod resulted from decreased serotonin content and suppressed expression of melatonin biosynthetic pathway enzymes, such as tryptophan hydroxylase and arylalkylamine-Nacetyltransferase in the pineal gland of ewes (Herman et al 2017).…”

“…It is worth mentioning that immune-melatonin interactions are bilateral, and the circulating concentration of melatonin may also be influenced by inflammatory condition (Skwarlo-Sonta et al 2008). However, the present experiment showed that endotoxin-induced inflammation more potently influence the nocturnal release of melatonin in ewes during LD compared with the SD period, and this observation is fully consistent with our previous study on ewes (Herman et al 2017).…”

“…The effect of endotoxin treatment on the MT1 gene expression does not have to result directly from the activation of the immune response, but it may be caused by the stress reaction triggered by the administration of LPS. Numerous studies showed that the peripheral injection of endotoxin strongly increases the circulating level of cortisol, which indicates activation of the stress response (Herman et al 2010(Herman et al , 2013b(Herman et al , 2016b(Herman et al , 2017. Because it was previously shown that stress is a potent suppressor of MT1 expression (Tenn and Niles 1993), it could be suggested that strength of the stress response released by LPS treatment determines its effect on the MT1 gene expression in the PT.…”

“…In vertebrates, melatonin is a hormone predominantly synthesized by pinealocytes of the pineal gland, and the secretion occurs after dark and rapidly stops after the sunrise (Todini et al 2010). Studies on sheep showed that the highest level and the longest period of melatonin secretion occur in winter during the short day photoperiod (breeding season), whereas the lowest concentration and the shortest duration of melatonin are found in the summer during long day photoperiod (seasonal anestrus) (Reiter et al 2009;Herman et al 2016aHerman et al , 2017Król et al 2016). Although the impact of melatonin on the reproductive function is undeniable, till now the main mechanism by which this hormone affects the HPG axis activity has not been clearly defined.…”

Immune‐pineal axis – acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes

“…This localization exposes pinealocytes and associated glial cells to circulating PAMPs, DAMPs and cytokines. Indeed, LPS inhibits melatonin synthesis in rats (Tamura et al, 2010), hamsters (Laranjeira-Silva et al, 2015) and chicken (Piesiewicz et al, 2012), X-irradiation in rats (Barfuss et al, 1969), IL-1β in ewes (Herman et al, 2017) and TNF in humans (Pontes et al, 2006).…”