Effects of Carnitines on Rat Sertoli Cell Protein Metabolism

Abstract

The influence of carnitine on male reproductive function is well established. However, the molecular mechanism by which carnitines control male fertility have not yet been clearly identified. In the present study, we studied the role of carnitines at testis level by examining their effects on protein metabolism in cultured rat Sertoli cells. Our results demonstrate that L-carnitine and, in particular, L-acetylcarnitine administration affects overall protein synthesis, inducing a dose-dependent decrease in amino acid incorporation and consequently an increase of the intracellular amino-acid pool useful to speed up Sertoli cell energy metabolism. We also observed significant effect on the expression of specific proteins involved in the regulation of glucose uptake and Insulin-like Growth Factor (IGF) biological activity. Actually, an increased expression of the mRNA coding for the membrane Glucose Transporter-1 (GLUT-1) and a decreased expression of mRNA coding for the negative modulator insulin-like growth factor-binding protein-4 (IGFBP-4) were induced by in vitro treatment with L-carnitine and L- acetylcarnitine separately and in combination; in fact, the effects observed were far more pronounced following concomitant treatment with both compounds. Taken together, these data indicate that the influence of carnitines on male fertility could be partly mediated by an activity at Sertoli cell level.

Key words

Sertoli cell - Male reproductive function - Testis - GLUT-1 - IGFBP-4

References

• 1 Brooks D E. Carnitine in male reproductive tract and its relation to the metabolism of the epididymis and spermatozoa. In: Frenkel RA, McGarry JD (eds) Carnitine biosynthesis, metabolism and functions. New York; Academic Press 1980: 219-235
• 2 Menchini Fabris G F, Canale D, Izzo P L, Olivieri L, Bartelloni M. Free L-carnitine in human semen: its variability in different andrologic pathologies.  Fertil Steril. 1984;  42 263-267
• 3 Borman M S, du Toit D, Otto B, Muller H, Hurter P, du Plessis D J. Seminal carnitine, epididymal function and spermatozoal motility.  S Afrr Med J. 1989;  75 20-21
• 4 Bremer J. Carnitine - metabolism and function.  Physiol Rev. 1983;  63 1420-1480
• 5 Costa M, Canale D, Filicori M, D’Iddio S, Lenzi A. L-carnitine in idiopatic asthenozoospermia: a multicenter study.  Andrologia. 1994;  26 155-159
• 6 Palmero S, Prati M, Costa M, Messeni Leone M, Fugassa E, De Cecco L. The effect of L-acetylcarnitine on some reproductive functions in the oligoasthenospermic rat.  Horm Metab Res. 1990;  22 622-626
• 7 Griswold M D. Unique aspects of the biochemistry and metabolism of Sertoli cells. In: Russel LD, Griswold MD (eds) The Sertoli Cell. Clearwater; Cache River Press 1993: 485-492
• 8 Palmero S, Bottazzi C, Costa M, Leone M, Fugassa E. Metabolic effects of L-carnitine on prepubertal rat in Sertoli cells.  Horm Metab Res. 2000;  32 87-90
• 9 Galdieri M, Ziparo E, Palombi F, Russo A M, Stefanini M. Pure Sertoli cell cultures: a new model for the study of somatic-germ cell interaction.  J Androl. 1981;  2 249-254
• 10 Palombi F, DiCarlo C. Alkaline phosphatase is a marker for myoid cells in cultures of rat peritubular and tubular tissue.  Biol Reprod. 1988;  39 1101-1105
• 11 Hartree E F. Determination of protein. A modification of the Lowry method that gives a linear photometric response.  Anal Biochem. 1972;  48 422-427
• 12 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.  Anal Biochem. 1987;  162 156-159
• 13 Fugassa E, Palmero S, Gallo G. Triiodothyronine decreases the production of androgen binding protein by rat Sertoli cells.  Biochem Biophys Res Commun. 1987;  143 241-247
• 14 Adashi E Y, Resnick C E, Hurwitz A, Ricciarelli E, Hernandez E R, Roberts C T, Leroith D, Rosenfeld R. The ovarian and testicular IGF-I system: a comparative analysis. In: Nieschlag E, Habenicht UF (eds) Spermatogenesis, Fertilization, Contraception. Berlin; Springer-Verlag 1992: 143-168
• 15 Bardi G, Bottazzi C, Demori I, Palmero S. Thyroid hormone and retinoic acid induce the synthesis of Insulin-like Growth Factor-Binding Protein-4 (IGFBP-4) in prepubertal pig Sertoli cells.  Eur J Endocrinol. 1999;  141 637-643
• 16 Smith E P, Dickson B A, Chernausek S D. Insulin-like growth factor binding protein-3 secretion from cultured rat Sertoli cells: dual regulation by follicle stimulating hormone and insulin-like growth factor-I.  Endocrinology. 1990;  127 2744-2751
• 17 Ghizzoni L, Barreca A, Mastorakos G, Furlini M, Vottero A, Ferrari B, Chrousos G P, Bernasconi S. Leptin inhibits steroid biosynthesis by human granulosa-lutein cells.  Horm Metab Res. 2001;  33 323-328
• 18 Enomoto A, Wempe M F, Tsuchida H, Shin H J, Cha S H, Anzai N, Goto A, Sakamoto A, Niwa T, Kanai Y, Anders M W, Endou H. Molcular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition.  J Biol Chem. 2002;  277 36 262-36 271