Germ cells regulate 3-hydroxybutyrate production in rat Sertoli cells

Paracrine regulation of Sertoli cell function by germ cells is an outstanding characteristic of testicular physiology. It has been demonstrated that Sertoli cells produce ketone bodies and that germ cells may use them as energy source. The aim of the study was to analyze a possible regulation by germ cells of ketogenesis in Sertoli cells. Cultures of Sertoli cells (SC) obtained from 31-day-old rats were co-cultured with germ cells (GC). The results presented herein show that the presence of GC stimulated 3-hydroxybutyrate production and increased mRNA levels of two enzymes involved in ketogenesis-carnitine palmitoyltransferase 1a (CPT1a) and mitochondrial 3-hydroxy-3-methylglutaryl-CoA (mHMGCoA) synthase- in SC. Additionally, GC increased monocarboxylate transporter 4 (Mct4) expression in SC, a transporter involved in ketone bodies exit. To evaluate if the observed effects might be mediated by soluble factors, SC cultures were incubated with germinal cell-conditioned medium (GCCM) or with two growth factors, bFGF and IGF1, which are known to be secreted by GC. We observed that GCCM and bFGF stimulated ketone bodies production but that IGF1 did not modify it. Also, we observed that GCCM and bFGF increased Cpt1a and Mct4 mRNA levels. In summary, results presented herein demonstrate that Sertoli cells are able to produce ketone bodies and that its production is regulated in a paracrine way by germ cells. This study adds new information about communication between Sertoli cells and developing germ cells.