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Testis |
Institut National pour la Santé et la Recherche Médicale INSERM U-407,2 Faculté de Médecine Lyon-Sud, Oullins Cedex, France
Institut de Physiologie,3 Université de Lausanne, Lausanne, Switzerland
Department of Biochemistry,4 St. Jude Children's Research Hospital, Memphis, Tennessee 38105
During spermatogenesis, postmeiotic germ cells utilize lactate produced by Sertoli cells as an energy metabolite. While the hormonal regulation of lactate production in Sertoli cells has been relatively well established, the transport of this energy substrate to the germ cells, particularly via the monocarboxylate transporters (MCTs), as well as the potential endocrine control of such a process remain to be characterized. Here, we report the developmentally and hormonally regulated expression of MCT2 in the testis. At Day 18, MCT2 starts to be expressed in germ cells as detected by Northern blot. The mRNA are translated into protein (40 kDa) in elongating spermatids. Ultrastructural analysis demonstrated that MCT2 protein is localized to the outer face of the cell membrane of spermatid tails. MCT2 mRNA levels are under the control of the endocrine, specifically follicle-stimulating hormone (FSH) and testosterone, and paracrine systems. Indeed, a 35-day-old rat hypophysectomy resulted in an 8-fold increase in testicular MCT2 mRNA levels. Conversely, FSH and LH administration to the hypophysectomized rats reduced MCT2 mRNA levels to the basal levels observed in intact animals. The decrease in MCT2 mRNA levels was confirmed in vitro using isolated seminiferous tubules incubated with FSH or testosterone. FSH or testosterone inhibited in a dose-dependent manner MCT2 mRNA levels with maximal inhibitory doses of 2.2 ng/ml and 55.5 ng/ml for FSH and testosterone, respectively. In addition to the endocrine control, TNF
and TGFß also exerted an inhibitory effect on MCT2 mRNA levels with a maximal effect at 10 ng/ml and 6.6 ng/ml for TGFß and TNF, respectively. Together with previous studies, the present data reinforce the concept that among the key functions of the endocrine/paracrine systems in the testis is the control of the energy metabolism occurring in the context of Sertoli cell–germ cell metabolic cooperation where lactate is produced in somatic cells and transported to germ cells via, at least, MCT2.
5 Correspondence: Mohamed Benahmed, INSERM U-407, Faculté de Médecine Lyon-Sud, BP 12, F-69921 Oullins Cedex. France. FAX: (+33) 4 78 86 31 16; benahmed{at}grisn.univ-lyon1.fr
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