Amylin regulates testosterone levels via steroidogenesis-related enzymes in the central nervous system of male mice. (December 2022)

• Record Type: Journal Article
• Authors: Chen, Yujie; Li, Qiang; Li, Xiaojing; Liu, Haodong; Li, Penghui; Hai, Rihan; Guo, Yongqing; Wang, Siwei; Wang, Kun; Du, Chenguang
• Is Part Of: Neuropeptides. Volume 96(2022)
• Publication Date: 2022-12
• Subjects: Amylin -- Steroidogenesis-related enzymes -- 3β-hydroxysteroid dehydrogenase -- Cytochrome P450 17A1 -- Steroidogenic acute regulatory protein -- Phospho-extracellular signal-regulated kinase; 3V Third ventricle -- 3β-HSD 3β-hydroxysteroid dehydrogenase -- 4V Fourth ventricle -- AP Area postrema -- ARC Arcuate nucleus -- CNS Central nervous system -- CYP17A1 Cytochrome P450 17A1 -- D3V Dorsal 3rd ventricle -- DHEA Dehydroepiandrosterone -- DMH Dorsomedial nucleus of the hypothalamus -- DRN Dorsal raphe nucleus -- Ect Ectorhinal cortex -- ELISA Enzyme-linked immunosorbent assay -- ERK Extracellular signal-regulated kinase -- FL Flocculus -- GABA Gamma aminobutyric acid -- GAPDH Glyceraldehyde-3-phosphate dehydrogenase -- GnRH Gonadotropin-releasing hormone -- GRN Gigantocellular reticular nucleus -- HPA Hypothalamic-pituitary-adrenal axis -- HPG Hypothalamic-pituitary-gonadal axis -- HY Hypothalamus -- I.p. Intraperitoneally -- IACUC Institutional Animal Care and Use Committee -- IR Immunoreactive -- LC Locus coeruleus -- LDT Lateral dorsal tegmental nucleus -- LHA Lateral hypothalamic area -- LHb Lateral habenula -- MAPK Mitogen-activated protein kinase family -- MARN Magnocellular reticular nucleus -- NDS Normal donkey serum -- NRM Nucleus raphe magnus -- NTS Nucleus tractus solitarii -- PBN Parabrachial nucleus -- PCG Pontine central gray -- PCRt Parvocellular reticular nucleus -- pERK phospho-Extracellular signal-regulated kinase -- PFL Paraflocculus -- PRh Perirhinal cortex -- PT Pyramidal tract -- PVN Paraventricular nucleus -- PVT Paraventricular nucleus of the thalamus -- RPa Raphe pallidus nucleus -- RSCg Granular retrosplenial cortex -- S1 Primary somatosensory cortex, barrel field -- S2 Secondary somatosensory cortex -- SAC Secondary auditory cortex -- SOC Superior olivary complex -- StAR Steroidogenic acute regulatory protein -- STN Spinal trigeminal nucleus, oral part -- TMN Trigeminal motor nucleus -- VI Abducens nucleus -- VII Facial nucleus -- VMH Ventromedial hypothalamic nucleus -- VTA Ventral tegmental area -- ZI Zona incerta; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2022.102288
• Languages: English
• ISSNs: 0143-4179

Abstract

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 ( p ERK). 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) p ERK 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. Highlights: The effect of amylin on testosterone levels was examined. Injection of amylin reduced the expression of steroidogenesis-related enzymes. Injection of amylin reduced the serum testosterone and increased the brain testosterone of male mice. Amylin regulates testosterone levels via steroidogenesis-related enzymes.