Stimulation of progesterone production in human granulosa-lutein cells by lipoproteins: evidence for cholesterol-independent actions of high-density lipoproteins.
Low-density lipoproteins (LDL) have been consistently reported to stimulate ovarian steroidogenesis, apparently by the provision of cholesterol as a steroidogenic substrate. Recent studies suggest that high-density lipoproteins (HDL) can also deliver cholesterol to support progesterone synthesis in human granulosa-lutein cells. Therefore, this study investigated the contributions of (i) cholesterol delivery, (ii) cyclic AMP and (iii) protein kinase C (PKC) in the steroidogenic responses of human granulosa-lutein cells to HDL and LDL. Over a 24-h treatment incubation, HDL stimulated a larger increase in progesterone output than did LDL at equivalent cholesterol concentrations. Moreover, at equal protein concentrations (100 microg protein/ml), HDL doubled progesterone production by cells co-treated with a maximally effective concentration of 22R-hydroxycholesterol, whereas LDL had no effect on the progesterone response to this membrane-permeable sterol. These observations indicate that the progesterone response to HDL is not solely due to the delivery of cholesterol as a steroidogenic substrate. Over 24 h, the stimulation of progesterone synthesis by HDL was additive with the response to a maximally effective concentration of dibutyryl-cAMP, but was unaffected by the down-regulation of PKC activity (by chronic pre-treatment with a tumour-promoting phorbol ester). We have concluded that HDL appears to stimulate progesterone production in human granulosa-lutein cells by a mechanism not solely reliant on cholesterol delivery.
Ragoobir
J
J
Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK. jragoobir@rvc.ac.uk
Abayasekara
D R E
DR
Bruckdorfer
K R
KR
Michael
A E
AE
D000704:Analysis of Variance; D003994:Bucladesine / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism; D013268:Stimulation, Chemical
D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C003585:22-hydroxycholesterol; D011374:Progesterone; D003994:Bucladesine; D011493:Protein Kinase C