Regulation of ketone bodies production in rat Sertoli cells.

RIERA MF; PELLIZZARI EH; REGUEIRA M; GALARDO MN; MERONI SB; CIGORRAGA SB

Torino

Congreso; 36th FEBS Congress; 2011

the Federation of European Biochemical Societies

Sertoli cells (SC) serve as nursing cells for developing germ cells (GC) and are under hormonal and paracrine regulation. The provision by SC of adequate levels of energy substrates for GC development is essential. It is known that SC produce ketone bodies (KB) and that GC express a specific isoform of succinil-CoA transferase (SCOT-t), which metabolizes KB in order to obtain energy. Two essential enzymes in KB production are carnitine palmitoyl transferase I (CPT I) and 3-hydroxy-3-methyl-glutaryl CoA synthase (mHMG-CoA-s). The presence of these enzymes in the testis has been demonstrated. The aim of this study was: (i0) to analyze the presence of CPT I and of mHMG-CoA-s in SC and (ii) to evaluate the regulation of KB production and of CPT I and mHMG-CoA-s expression by GC and bFGF ?one of the growth factors secreted by GC. SC cultures obtained from 31-day-old rats were maintained under basal conditions (B), co-cultured with GC ?obtained from the same animals-, or incubated with bFGF (30 ng/ml). KB production was estimated by the determination of 3-b-hydroxybutirate levels in conditioned media; CPT I and mHMG-CoA-s mRNA levels were determined by Northern Blot. Incubation of SC with GC (SC/GC) for 48 hours increased KB production (B: 8.1±1.4, CG/SC: 19.1±3.2 mM/mg DNA*; X±DS, n=3, *p<0.01). Presence of CPT I and mHMG-CoA-s in SC and up-regulation by GC were demonstrated. Stimulation of SC with bFGF for 72 hours increased KB production (B: 15.1±3.5, bFGF: 22.3±1.8 mM/mg DNA*; X±SD, n=3, p<0.05) and this increase was preceded by an increase of CPT I expression. Altogether, these results suggest that GC might regulate KB production in SC by modulating CPT I and mHMG-CoA-s expression. Since bFGF exerted similar effects on KB production and gene expression, it is tempting to speculate that this growth factor may be involved in paracrine regulation of energy status in the seminiferous tubules.