The suppressive effect of immune stress on LH secretion is absent in the early neonatal period in rats

Some physiological functions display weak responses to stress in the early neonatal period; i.e., theyexhibit stress hyporesponse periods. In this study, we evaluated whether gonadotropin regulatory fac-tors exhibit stress hyporesponsive periods in male and female rats. Rats were intraperitoneally injectedwith lipopolysaccharide (100 μg/kg) (LPS group) or saline (control group) on postnatal day (PND) 5,10, 15, or 25. Then, their serum luteinizing hormone (LH) concentrations and hypothalamic mRNAlevels of gonadotropin regulatory factors; i.e., kisspeptin (Kiss1), the kisspeptin receptor (Kiss1r), andgonadotropin-releasing hormone (GnRH), were measured at 2 h after the injection. The hypothalamicmRNA levels of pro-inflammatory cytokines were also measured because they suppress gonadotropinsecretion. The serum LH concentration of the LPS group was lower than that of the control group atPND25 in both sexes, but no such difference was seen at PND5, 10, or 15 in either sex. In both sexes,the hypothalamic tumor necrosis factor (TNF)α and interleukin (IL)-6 mRNA expression levels of the LPSgroup were higher than those of the control group at PND25, but not at PND5 or 10. The hypothalamicIL-1β mRNA expression level of the LPS group was higher than that of the control group at all time points. The hypothalamic Kiss1, Kiss1r, and GnRH mRNA expression levels of the LPS and control groups did notdiffer at any time point in either sex. These findings suggest that gonadotropin regulatory factors exhibitstress hyporesponse periods. The hypothalamic–pituitary–gonadal axis (HPG) might become responsiveto immune stress between PND15 and 25, which could be related to enhanced hypothalamic cytokineexpression. The avoidance of infectious stress during the early neonatal period might be important fornormal development of the HPG axis.

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本論文は, 著者Munkhsaikhan Munkhzayaの学位論文として提出され, 学位審査・授与の対象となっている。