Involvement of Cytokine-Induced Neutrophil Chemoattractant in Hypothalamic Thermoregulation of Luteinizing Hormone-Releasing Hormone

Abstract

We demonstrated in a previous study that serum IL-8 concentrations were significantly higher in women with hot flashes than without hot flashes. To clarify the role of IL-8 in the pathoetiology of menopausal hot flashes, we examined the effect of rat cytokine-induced neutrophil chemoattractant (CINC), a member of the IL-8 family, on thermoregulation using ovariectomized (OVX) rats treated with intracerebroventricular (i.c.v.) injection of LHRH agonist (LHRHa) as a model of hot flashes. We found that: 1) expression of CINC mRNA was increased around the periventricular area in the hypothalamus at 1 h, and the serum CINC concentration was increased at 2 h after i.c.v. injection of LHRHa; 2) the increase in serum CINC concentration in hypophysectomized rats was significantly lower than that in sham-operated rats; 3) i.c.v. but not iv injection of CINC elevated the rectal temperature of OVX rats; 4) i.c.v. injection of LHRHa into OVX rats produced a rapid rise (maximal increase: 10-25 min) in tail skin temperature, and the elevation was augmented by injection of an anti-CINC antibody; and 5) changes in serum CINC concentration and skin temperature after i.c.v. injection of LHRHa were reversed by replacement of estradiol. In conclusion, the production of CINC in the hypothalamus due to LHRHa injection in OVX rats was increased after elevation of skin temperature, suggesting that CINC plays a key role in the homeostasis of body temperature. Disturbance of the thermoregulatory mechanism involving LHRH and CINC may be related to the pathoetiology of hot flashes.

Effects of oral and transdermal estrogen therapies on circulating cytokines and chemokines in postmenopausal women with hysterectomy

“…In addition, we showed that oral ET increased IL-8 level, but that transdermal ET decreased IL-8 level. In our previous study, we found that elevated level of cytokine-induced neutrophil chemoattractant, a member of the IL-8 family, was reduced by E 2 and that elevated skin temperature in ovariectomized rats was reduced by treatment with injection of a luteinizing hormone-releasing hormone agonist (22). This result observed in rats was also observed in women with hot flashes in the transdermal group in the present study.…”

Urocortin 1 reduces food intake and ghrelin secretion via CRF2 receptors

“…Interestingly, although both the decreased level of plasma acylated ghrelin and the elevated level of gastric body acylated ghrelin were restored to basal levels 4 h after icv injection of UCN, the levels of des-acylated ghrelin were not restored. Ghrelin-producing cells exist as two types in the rat gastrointestinal tract (26), closed-and opened-type cells. Acylated ghrelin exists in closed-type cells, while des-acylated ghrelin exists in both closed-and opened-type cells (25).…”

“…Quantitative gene expression analysis was performed by real-time RT-PCR according to a procedure described previously (26). TaqMan Gene Expression Master Mix (Applied Biosystems) and Assays-on-Demand Gene Expression probes (GHRL: Rn00572319_m1; FOS: Rn02396759_m1; S18rRNA: Hs99999901_s1; RPS29: Rn00820645_g1; Applied Biosystems) were used in subsequent PCR reactions according the manufacturer's instructions.…”

“…Following perfusion, the rat brains were dissected. Fixed whole brains were cut along the coronary plane, embedded in paraffin, and sectioned at 6 m. Paraffin-embedded tissue blocks and sections of rat brain for in situ hybridization were prepared according to procedures described previously (26). The cDNA template used for Fos was a 458-base pair fragment corresponding to bases 884 -1341 of Fos cDNA (GenBank accession no.…”

Mechanism of hot flashes

“…Recently it has been demonstrated than serum IL-8 concentrations were signifi cantly higher in women with hot fl ashes than those without. IL-8 could play an important role in the pathoaetiology of hot fl ashes [34,35].…”