Leukemia inhibitory factor-receptor signalling negatively regulates gonadotrophin-stimulated testosterone production in mouse Leydig Cells. (15th March 2022)

• Record Type: Journal Article
• Authors: Curley, Michael; Darbey, Annalucia; O'Donnell, Liza; Kilcoyne, Karen R.; Wilson, Kirsten; Mungall, Will; Rebourcet, Diane; Guo, Jingtao; Mitchell, Rod T.; Smith, Lee B.
• Is Part Of: Molecular and cellular endocrinology. Volume 544(2022)
• Publication Date: 2022-03-15
• Subjects: Testis -- Paracrine -- Cytokine -- Steroidogenesis -- Leydig cells; LIF Leukemia Inhibitory Factor -- LIFR Leukemia Inhibitory Factor Receptor -- IL6ST Interleukin 6 Cytokine Family Signal Transducer -- PTM Peritubular Myoid Cell -- SC Sertoli Cell -- LC Leydig Cell -- T Testosterone -- LH Luteinizing Hormone -- HPG Hypothalamic, Pituitary, Gonadal (axis) -- WT Wild-type -- LC Lifr-KO Leydig cell Lifr knock-out -- Ad Adenovirus -- Cre Cyclic Recombinase -- GFP Green Fluorescent Protein -- RFP Red Fluorescent Protein -- Lhcgr Luteinizing Hormone/Chorionic Gonadotrophin Receptor -- Star Steroidogenic Acute Regulatory Protein -- Cyp11a1 P450 Cholesterol Side-chain Cleavage Enzyme -- Hsd3b1/6 Hydroxysteroid Dehydrogenase 3-β Type 1/6 -- Cyp17a 17α-hydroxylase, 17, 20-lyase -- Hsd17b3 Hydroxysteroid Dehydrogenase 17-β Type 3; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2022.111556
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Testicular Leydig cells (LCs) are the principal source of circulating testosterone in males. LC steroidogenesis maintains sexual function, fertility and general health, and is influenced by various paracrine factors. The leukemia inhibitory factor receptor (LIFR) is expressed in the testis and activated by different ligands, including leukemia inhibitory factor (LIF), produced by peritubular myoid cells. LIF can modulate LC testosterone production in vitro under certain circumstances, but the role of consolidated signalling through LIFR in adult LC function in vivo has not been established. We used a conditional Lifr allele in combination with adenoviral vectors expressing Cre-recombinase to generate an acute model of LC Lifr- KO in the adult mouse testis, and showed that LC Lifr is not required for short term LC survival or basal steroidogenesis. However, LIFR-signalling negatively regulates steroidogenic enzyme expression and maximal gonadotrophin-stimulated testosterone biosynthesis, expanding our understanding of the intricate regulation of LC steroidogenic function. Highlights: The leukemia inhibitory factor receptor gene ( Lifr ) was acutely ablated from Leydig cells in adult mouse testes. Wildtype mouse Leydig cells highly express genes required for LIFR signalling that can be activated via multiple ligands. LIFR signalling is not required for short term Leydig cell survival or basal steroidogenesis in the adult testis. LIFR signalling negatively regulates steroidogenic gene expression and gonadotrophin-stimulated testosterone synthesis.