title: The suppressive effect of immune stress on LH secretion is absent in the early neonatal period in rats.
abstract: Some physiological functions display weak responses to stress in the early neonatal period; i.e., they exhibit stress hyporesponse periods. In this study, we evaluated whether gonadotropin regulatory factors exhibit stress hyporesponsive periods in male and female rats. Rats were intraperitoneally injected with lipopolysaccharide (100μg/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 mRNA levels of gonadotropin regulatory factors; i.e., kisspeptin (Kiss1), the kisspeptin receptor (Kiss1r), and gonadotropin-releasing hormone (GnRH), were measured at 2h after the injection. The hypothalamic mRNA levels of pro-inflammatory cytokines were also measured because they suppress gonadotropin secretion. The serum LH concentration of the LPS group was lower than that of the control group at PND25 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 LPS group were higher than those of the control group at PND25, but not at PND5 or 10. The hypothalamic IL-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 not differ at any time point in either sex. These findings suggest that gonadotropin regulatory factors exhibit stress hyporesponse periods. The hypothalamic-pituitary-gonadal axis (HPG) might become responsive to immune stress between PND15 and 25, which could be related to enhanced hypothalamic cytokine expression. The avoidance of infectious stress during the early neonatal period might be important for normal development of the HPG axis.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Munkhsaikhan
authors.initials: M
authors.lastname: Munkhzaya
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwasa
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Altankhuu
authors.initials: A
authors.lastname: Tungalagsuvd
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Kawami
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kuwahara
authors.affiliation: Department of Obstetrics and Gynecology, The University of Tokushima Graduate School, Institute of Health Biosciences, 3-18-15 Kuramoto-Cho, Tokushima 770-8503, Japan. Electronic address: mat@tokushima-u.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Irahara
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D007107:Immune System / Q000187:drug effects / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D012737:Sex Factors; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D016207:Cytokines; C491406:Kiss1 protein, rat; C492247:Kiss1r protein, rat; D059648:Kisspeptins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone
keywords: Cytokines; HPG axis; Hyporesponsive period; LH; LPS; Stress