Effect of gossypol on cultured TM3 Leydig and TM4 Sertoli cells: 31P and 23Na NMR study.
The effects of gossypol on glucose metabolism, ATP levels and intracellular sodium levels in murine TM3 Leydig and TM4 Sertoli cell lines were investigated, and their response compared. Relative ATP levels and sodium ion levels in the two cell lines were determined by 31P and 23Na NMR spectroscopy. Short-term effect of gossypol on phosphate metabolism in immobilized and perfused cells was apparent in 31P NMR spectra only with relatively high concentrations of gossypol, corresponding to about 40 times IC50. However, incubation with low gossypol concentrations markedly affected the energetic status of the cells, especially of the TM3 cells. Although inhibition of proliferation by gossypol was stronger with the TM4 cells, the decrease of intracellular ATP level and increase of sodium ion concentration were more pronounced in the TM3 cells. The growth-inhibitory effect of (-)-gossypol was stronger than that of (+)-gossypol, with the eudesmic ratio of 2-2.5. The enantioselectivity of the effect of gossypol on the energy metabolism of TM3 and TM4 cells was low, in contrast to the in vivo antispermatogenic effect, which was reported to be solely associated with (-)-gossypol. Inhibition of energy production in somatic testicular tissue is thus unlikely to be major cause of the antispermatogenic effect of gossypol.
Department of Medicinal Chemistry, Royal Danish School of Pharmacy, Copenhagen, Denmark.
L L
LL
Hansen
J W
JW
Jaroszewski
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006072:Gossypol / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051379:Mice; D010758:Phosphorus; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D012975:Sodium Isotopes; D013237:Stereoisomerism
D012975:Sodium Isotopes; D010758:Phosphorus; D000255:Adenosine Triphosphate; D012964:Sodium; D005947:Glucose; D006072:Gossypol