The sex-specific patterns of changes in hypothalamic-pituitary-gonadal axis during experimental autoimmune encephalomyelitis

•In both sexes, EAE induces expression of inflammatory markers in the hypothalamus.•EAE induces sex-specific changes in HPG axis with a common feature: low LH levels.•EAE induces sex-specific downregulation of Kiss1 and Gnrh1 mRNA expression.•EAE upsets estrous cycle; not affecting estradiol, increa...

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Published in:Brain, behavior, and immunity behavior, and immunity, 2020-10, Vol.89, p.233-244
Main Authors: Milosevic, Ana, Janjic, Marija M., Lavrnja, Irena, Savic, Danijela, Bozic, Iva D., Tesovic, Katarina, Jakovljevic, Marija, Pekovic, Sanja, Stojilkovic, Stanko S., Bjelobaba, Ivana
Format: Article
Language:English
Subjects:
Animals
Encephalomyelitis, Autoimmune, Experimental
Estrous cycle
Experimental autoimmune encephalomyelitis
Female
Gonadotropin releasing hormone
Hypothalamic-pituitary gonadal axis
Hypothalamus
Kisspeptin
Luteinizing Hormone
Male
Multiple sclerosis
Rats
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Summary:•In both sexes, EAE induces expression of inflammatory markers in the hypothalamus.•EAE induces sex-specific changes in HPG axis with a common feature: low LH levels.•EAE induces sex-specific downregulation of Kiss1 and Gnrh1 mRNA expression.•EAE upsets estrous cycle; not affecting estradiol, increasing progesterone levels.•Males with EAE show lower testosterone levels and lower capacity for LH release. 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.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2020.06.025