The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis.
2020
Authors:
Milošević, AnaJanjić, Marija
Lavrnja, Irena
Savić, Danijela
Božić, Iva
Milošević, Katarina
Jakovljević, Marija
Peković, Sanja
Stojilkovic, Stanko S.
Bjelobaba, Ivana
Document Type:
Article (Published version)
,
© 2020 Elsevier Inc.
Metadata
Show full item recordAbstract:
Multiple sclerosis develops during reproductive years in a sex-specific manner. Various neuroendocrine changes have been described in this inflammatory, demyelinating, and debilitating disease. We here aimed to determine the extent and sex specificity of alterations in the hypothalamic-pituitary-gonadal axis in the rat model of multiple sclerosis named experimental autoimmune encephalomyelitis. During the disease course, the hypothalamic tissue showed transient upregulation of inflammatory marker genes Gfap, Cd68, Ccl2, and Il1b in both sexes, but accompanied by sex-specific downregulation of Kiss1 (in females only) and Gnrh1 (in males only) expression. In females, the expression of gonadotrope-specific genes Lhb, Cga, and Gnrhr was also inhibited, accompanied by decreased basal but not stimulated serum luteinizing hormone levels and a transient arrest of the estrous cycle. In contrast, Fshb expression and serum progesterone levels were transiently elevated, findings consistent with the maintenance of the corpora lutea, and elevated immunohistochemical labeling of ovarian StAR, a rate limiting protein in steroidogenic pathway. In males, downregulation of Gnrhr expression and basal and stimulated serum luteinizing hormone and testosterone levels were accompanied by inhibited testicular StAR protein expression. We propose that inflammation of hypothalamic tissue downregulates Kiss1 and Gnrh1 expression in females and males, respectively, leading to sex-specific changes downstream the axis.
Keywords:
Estrous cycle; Experimental autoimmune encephalomyelitis; Gonadotropin releasing hormone; Hypothalamic-pituitary gonadal axis; Kisspeptin; Luteinizing hormone; Multiple sclerosisSource:
Brain, Behavior, and Immunity, 2020, 89, 233-244Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Intramural Research Program of the National Institute of Child Health and Human Development, NIH , Project ZIA HD 000195-25
Related info:
DOI: 10.1016/j.bbi.2020.06.025
ISSN: 0889-1591
PubMed: 32592862