title: Melatonin alters the glycolytic profile of Sertoli cells: implications for male fertility.
abstract: Melatonin co-operates with insulin in the regulation of glucose homeostasis. Within the testis, glucose metabolism in the somatic Sertoli cells (SCs) is pivotal for spermatogenesis. Since the effects of melatonin on male reproductive physiology remain largely unknown, we hypothesized that melatonin may affect spermatogenesis by modulating SC metabolism, interacting with insulin. To test our hypothesis, rat SCs were maintained in culture for 24 h in the presence of insulin, melatonin or both and metabolite production/consumption was determined by proton nuclear magnetic resonance ((1)H-NMR). Protein levels of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were determined by western blot. LDH activity was also assessed. SCs treated with melatonin showed an increase in glucose consumption via modulation of GLUT1 levels, but decreased LDH protein expression and activity, which resulted in lower lactate production. Moreover, SCs exposed to melatonin produced and accumulated less acetate than insulin-exposed cells. The combined treatment (insulin plus melatonin) increased acetate production by SCs, but intracellular acetate content remained lower than in insulin exposed cells. Finally, the intracellular redox state, as reflected by intracellular lactate/alanine ratio, was maintained at control levels in SCs by melatonin exposure (i.e. melatonin, alone or with insulin, increased the lactate/alanine ratio versus cells treated with insulin). Furthermore, SCs exposed to insulin plus melatonin produced more lactate and maintained the protein levels of some glycolysis-related enzymes and transporters at control levels. These findings illustrate that melatonin regulates SCs metabolism, and thus may affect spermatogenesis. Since lactate produced by SCs provides nutritional support and has an anti-apoptotic effect in developing germ cells, melatonin supplementation may be an effective therapy for diabetic male individuals facing subfertility/infertility.
authors.affiliation: CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Cátia S
authors.initials: CS
authors.lastname: Rocha
authors.affiliation: CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Martins
authors.affiliation: CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Rato
authors.affiliation: CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Branca M
authors.initials: BM
authors.lastname: Silva
authors.affiliation: CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal pfobox@gmail.com alvesmarc@gmail.com.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Oliveira
authors.affiliation: CICS-UBI, Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal pfobox@gmail.com alvesmarc@gmail.com.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D007248:Infertility, Male / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D007328:Insulin; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; D007770:L-Lactate Dehydrogenase; D010732:Phosphofructokinase-1; D005947:Glucose; D008550:Melatonin
keywords: Sertoli; glycolysis; male reproductive function; melatonin; metabolism