Regulation of Leydig cells through a steroidogenic acute regulatory protein-independent pathway by a lipophilic factor from macrophages.
The purpose of this investigation was to study the mechanism of action of a macrophage-derived factor that stimulates steroid production by Leydig cells. This factor increased testosterone production within 30 min, and reached a half-maximal response by 6-8 h. At a maximal dose, it stimulated testosterone production 20-fold at 24 h. Its efficacy was consistently higher than that achieved with a maximal dose of human chorionic gonadotropin (hCG). However, Leydig cells treated with a maximal dose of both the macrophage-derived factor and hCG secreted the same amount of testosterone as when given a maximal dose of only the macrophage-derived factor. The macrophage-derived factor did not require new protein synthesis to stimulate testosterone production, nor did it alter the amount of steroidogenic acute regulatory protein (StAR). While the macrophage-derived factor required an active cholesterol side-chain cleavage complex system, it did not alter the capacity of this enzyme complex. Finally, the macrophage-derived factor was unable to stimulate the production of progesterone by isolated mitochondria. In summary, the macrophage-derived factor is a highly active, acute regulator of steroidogenesis that acts through a high capacity StAR-independent pathway.
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock 79430, USA.
Y O
YO
Lukyanenko
A M
AM
Carpenter
D E
DE
Brigham
D M
DM
Stocco
J C
JC
Hutson
D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors; D002460:Cell Line; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007985:Leydig Cells / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D010750:Phosphoproteins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013739:Testosterone / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein
D047072:Aromatase Inhibitors; D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D000616:Aminoglutethimide; D013739:Testosterone; D002786:Cholesterol Side-Chain Cleavage Enzyme