The Hypothalamic-Pituitary-Gonadal Axis Is Suppressed During Experimental Autoimmune Encephalomyelitis in Male Rats
2024
Autori:
Milošević, AnaSavić, Danijela
Lavrnja, Irena
Milošević, Katarina
Bjelobaba, Ivana
Janjić, Marija
Ostala autorstva
Gotti, StefanoTip dokumenta:
Konferencijski prilog (Objavljena verzija)
,
© 2024 by the Dipartimento di Scienze Farmacologiche e Biomolecolari, Milan
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Multiple sclerosis (MS) is an autoimmune disease that usually occurs in both sexes during
the reproductive years. Various neuroendocrine changes have been described in this
inflammatory, demyelinating and debilitating disease, and many male MS patients have
lower blood testosterone levels. Our aim was to determine the extent of alterations in the
hypothalamic-pituitary-gonadal axis in the male rat model of MS, experimental autoimmune
encephalomyelitis (EAE). During the course of the disease, hypothalamic tissue showed a
transient upregulation of the inflammatory marker genes Gfap, Cd68, Ccl2 and Il1b,
accompanied by a downregulation of Gnrh1 expression and pituitary Gnrhr expression.
Serum levels of luteinizing hormone and testosterone were also reduced during the disease.
To better understand the causes of decreased testosterone production during EAE, we
examined the expression status of genes and proteins associated with steroidogenesis in the
testes. No changes in the number of interstitial cells were detected in the EAE animals, but
the expression of the gene insulin-like 3 was reduced at the peak of the disease, suggesting
that the functional capacity of Leydig cells was impaired. Consistent with this finding, the
expression of most steroidogenic enzyme genes and proteins was reduced during EAE,
including StAR, CYP11A1, CYP17A1 and HSD3B. No signs of testicular inflammation
were observed. Steroidogenesis recovered after the injection of hCG, a placental
gonadotropin or buserelin acetate, an analogue of gonadotropin-releasing hormone, at the
peak of EAE. Overall, our results are consistent with the hypothesis that impaired testicular
steroidogenesis originates upstream of the testes and that low serum LH levels are the main
cause of decreased testosterone levels during EAE.
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200007 (Univerzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
U:
- Gotti S, editor. Abstract of individual lectures and free contributions: 12th International Meeting Steroids and Nervous System; 2024 Feb 24-27; Torino, Italy. Milan: Dipartimento di Scienze Farmacologiche e Biomolecolari ; 2024. p. 124.