Mitochondria mediate amplification of luteinizing hormone action by adenosine in luteal cells.
Adenosine markedly amplifies the response of isolated rat and human luteal cells to LH via an intracellular site of action that is associated with an increase in cell ATP levels. This effect of adenosine is maximal in midstage cells and minimal at the onset of functional regression in late stage luteal cells. The objective of the present studies was to evaluate the role of mitochondria in mediating the action of adenosine in isolated rat luteal cells and to assess whether mitochondrial function may be compromised in regressing luteal cells. The present studies show that adenosine produced a significant increase in luteal cell levels of ADP and ATP, but had no effect on cell levels of GTP. Since ADP stimulates oxidative phosphorylation, we evaluated the role of mitochondria in mediating the amplification of LH action by adenosine in luteal cells with two mitochondrial inhibitors, oligomycin and dinitrophenol. Both inhibitors markedly reduced, in a dose-dependent manner, LH-stimulated cAMP accumulation in the presence or absence of adenosine. In parallel, both inhibitors decreased basal and adenosine-elevated ATP levels in a dose-related manner. Although late stage luteal cells showed a marked reduction in adenosine amplification of LH-stimulated cAMP accumulation, no change in adenosine-dependent elevation of cell levels of ATP was seen. We conclude that amplification of LH action and elevation of ATP levels in midstage cells by adenosine requires an increase in oxidative phosphorylation that is stimulated by an increase in cell levels of ADP. However, attenuation of adenosine amplification of LH action in late stage luteal cells is not due to impaired ATP production.
Soodak
L K
LK
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
Behrman
H R
HR
D019297:2,4-Dinitrophenol; D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003338:Corpus Luteum / Q000166:cytology* / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004140:Dinitrophenols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008928:Mitochondria / Q000187:drug effects*; D009840:Oligomycins / Q000494:pharmacology; D051381:Rats
D000227:Adenine Nucleotides; D004140:Dinitrophenols; D009840:Oligomycins; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000241:Adenosine; D019297:2,4-Dinitrophenol