Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats

Ana Milosevic,Iva D Bozic,Marija M Janjic,Marija Jakovljevic,Ivana Bjelobaba,Irena Lavrnja,Katarina Tesovic,Danijela Savic,Stanko S Stojilkovic

doi:10.1038/s41598-021-88305-5

Abstract

Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes. Many male patients with MS show lower blood testosterone levels, which was also observed in male rats during experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To better understand the causes of decreased testosterone production during EAE, we investigated the expression status of genes and proteins associated with steroidogenesis in the testes. No changes in the number of interstitial cells were observed in EAE animals, but the expression of the insulin-like 3 gene was reduced at the peak of the disease, implying that the Leydig cell functional capacity was affected. 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. Recovery of steroidogenesis was observed after injection of hCG, the placental gonadotropin, or buserelin acetate, a gonadotropin-releasing hormone analogue, at the peak of EAE. Together, our results are consistent with the hypothesis that impaired testicular steroidogenesis originates upstream of the testes and that low serum LH is the main cause of decreased testosterone levels during EAE.

Highlights

Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes
Testosterone biosynthesis is mainly regulated by luteinizing hormone (LH), which is secreted from the pituitary gland in response to gonadotropinreleasing hormone (GnRH), a hypothalamic decapeptide
Immunization resulted in a typical EAE course[9,24], with symptoms peaking on day 14 after immunization, and concomitant body weight loss with a nadir that coincides with the peak of the disease

Summary

Introduction

Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes. The acute phase of steroidogenesis, represented by increased mobilization and transport of cholesterol to the inner mitochondrial membrane, occurs within a few minutes after LH binding to its receptor. This phase is determined by the action of steroidogenic acute regulatory protein (StAR)[12,13]. The process of steroidogenesis involves two major enzyme groups: cytochrome P450 (CYPs), which catalyzes hydroxylation and cleavage reaction of steroid substrates, and hydroxysteroid dehydrogenases (HSDs), involved in steroid hormone reduction and oxidation reactions These enzymes are found on the inner mitochondrial and endoplasmic reticulum membranes. The chronic phase of steroidogenesis that occurs within a few hours involves mechanisms that increase transcription/ translation of these steroidogenic e nzymes[14,15]

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Conclusion