Amylin regulates testosterone levels via steroidogenesis-related enzymes in the central nervous system of male mice

Abstract

Amylin is a peripheral satiation signal polypeptide co-secreted with insulin by pancreatic β-cells in response to nutrient ingestion. Amylin participates in the eating-inhibitory effect and regulates energy metabolism by acting on the central nervous system (CNS). However, the role of amylin in regulating the biosynthesis of steroid hormones, such as testosterone, through the hypothalamic-pituitary-gonadal axis (HPG) remains unexplored. However, only limited evidence is available on the involvement of amylin in steroid synthesis, we hypothesize that amylin regulates testosterone levels via steroidogenesis-related enzymes in the CNS. In this study, we elucidated the effect of intraperitoneal injection of amylin on the protein expression of steroidogenesis-related enzymes, including 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome P450 17A1 (CYP17A1), and steroidogenic acute regulatory protein (StAR), and phospho-extracellular signal-regulated kinase (pERK). Additionally, the effect of amylin on testosterone levels in male mice was examined. Our results suggested that 3β-HSD and CYP17A1 neurons were widely expressed in the CNS of male mice, whereas StAR neurons were mainly expressed in the zona incerta (ZI) and locus coeruleus (LC) regions. Intraperitoneal injection of amylin significantly reduced (p < 0.01) the expression of 3β-HSD, CYP17A1, and StAR in ZI and other areas near the third ventricle (3 V) but increased (p < 0.01) pERK expression, brain testosterone levels, serum FSH, serum LH, and decreased (p < 0.01) serum testosterone levels in mice. In conclusion, amylin regulates testosterone levels via steroidogenesis-related enzymes in the central nervous system of male mice.

Keywords: 3β-hydroxysteroid dehydrogenase; Amylin; Cytochrome P450 17A1; Phospho-extracellular signal-regulated kinase; Steroidogenesis-related enzymes; Steroidogenic acute regulatory protein.