Stimulation of rat ovarian cell steroidogenesis by high density lipoproteins modified with tetranitromethane.
Human high density lipoprotein (devoid of apo-E) was modified by nitration of tyrosine residues with tetranitromethane. As a result of extensive cross-linking, monomeric apo-A-I was markedly depleted, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the modified HDL did not effectively bind to high-affinity sites present on dispersed rat ovarian cells and isolated rat ovarian membranes. Nonetheless, the modified HDL retained the ability to stimulate steroidogenesis by both dispersed rat ovarian cells and cultured rat granulosa cells to a degree at least equal to that of native HDL. Modified HDL stimulated luteal steroidogenesis under basal conditions and when cells were stimulated with luteinizing hormone or 8-bromo-cAMP. Although modified HDL did not effectively bind to high-affinity sites, it exhibited substantial "nonspecific" or "low-affinity" binding which was not displaceable by native HDL. These data suggest that high-affinity binding is not an essential event in the "HDL pathway" and that HDL can deliver its sterols through low-affinity cellular associations.
Nestler
J E
JE
Chacko
G K
GK
Strauss
J F
JF
D000818:Animals; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D008697:Methane / Q000031:analogs & derivatives*; D009928:Organ Specificity; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D011372:Progestins / Q000096:biosynthesis*; D016601:RNA-Binding Proteins; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D013774:Tetranitromethane / Q000494:pharmacology*
D002352:Carrier Proteins; D006063:Chorionic Gonadotropin; D006064:Gonadotropins, Equine; D008075:Lipoproteins, HDL; D011372:Progestins; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D013774:Tetranitromethane; D008697:Methane