Roles for prostaglandins in the steroidogenic response of human granulosa cells to high-density lipoproteins.
In human granulosa-lutein cells, high-density lipoproteins (HDL) can stimulate progesterone synthesis. The objective of the present study was to establish whether prostaglandins (PGs) participate in the steroidogenic response to HDL. Both HDL and apolipoprotein AI (ApoAI) stimulated concentration-dependent increases in PGE2, cAMP and progesterone accumulation. The minimum concentrations of HDL and ApoAI required to elevate PGE2 production were the same as those required to stimulate cAMP accumulation and progesterone synthesis. Concentrations of PGE2 were elevated within 10 min in cells exposed to HDL and rose progressively over 24 h, whereas cAMP and progesterone were only increased significantly after 24 h of treatment with HDL. Co-treatment with prostaglandin H synthase inhibitors (meclofenamic acid and indomethacin) abolished the cAMP and progesterone responses to both HDL and ApoAI. Hence, the ability of HDL to stimulate progesterone synthesis can be mimicked by ApoAI and appears to involve increased generation of one or more luteotrophic PGs, possibly acting via cAMP.
Chandras
Christina
C
Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK.
Ragoobir
Jennifer
J
Barrett
Gemma E
GE
Bruckdorfer
K Richard
KR
Graham
Annette
A
Abayasekara
D Robert E
DR
Michael
Anthony E
AE
D016632:Apolipoprotein A-I / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D051545:Cyclooxygenase 1; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins; D011374:Progesterone / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases; D013997:Time Factors
D016632:Apolipoprotein A-I; D007527:Isoenzymes; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011374:Progesterone; D000242:Cyclic AMP; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone