Diacylglycerols release LH: structure-activity relations reveal a role for protein kinase C.
A series of diacylglycerols were synthesized with varying lengths and substituents in order to establish the structure-activity relationship between each with activation of protein kinase C and stimulation of a biological response system (pituitary luteinizing hormone release). This approach enables distinction between actions mediated by direct activation of protein kinase C and those due to other, presumably nonspecific, actions. The ability of diacylglycerols to function as regulators of a biological response system (pituitary luteinizing hormone release) and of protein kinase C was investigated with a series of sn-1,2 diacylglycerols containing fatty acids 4-10 carbons in length and with analogs in which the 3' hydroxyl was replaced with a chloro, hydrogen, or sulfhydryl moiety. Several diacylglycerols stimulated LH release in a saturable, time and dose dependent manner that was independent of extra-cellular calcium. Dioctanoylglycerol (diC8) was the most effective of the diacylglycerols tested; 3' analogs lacking the hydroxyl were inactive. The diacylglycerols activated protein kinase C in vitro whereas the 3' analogs did not. These data implicate protein kinase C in the mechanism of LH release, demonstrate that unsaturated fatty acyl moieties within the diacylglycerol are not required for protein kinase C activation, and establish diacylglycerol-protein kinase C structure-function relationships that should prove useful for investigations in other systems.
Conn
P M
PM
Ganong
B R
BR
Ebeling
J
J
Staley
D
D
Neidel
J E
JE
Bell
R M
RM
D000818:Animals; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology*; D005260:Female; D005989:Glycerides / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D004075:Diglycerides; D005989:Glycerides; D007986:Luteinizing Hormone; D011494:Protein Kinases; D011493:Protein Kinase C