Vasoactive intestinal peptide (VIP)-mediated expression and function of steroidogenic acute regulatory protein (StAR) in granulosa cells.
VIP is a peptide hormone capable of activating the cAMP/PKA pathway and modifying gonadal steroidogenic capacity. Less is known about the molecular mechanisms of VIP-mediated steroidogenesis and its role in regulating the steroidogenic acute regulatory protein (STAR). We examined the impact of VIP on STAR expression and function in immortalized (KK1) and primary mouse granulosa cells, where VIP strongly upregulated STAR expression and steroidogenesis. Inhibitors of the PKA and PKC pathways suggested that both are activated by VIP. VIP did not efficiently phosphorylate STAR (P-STAR); however, VIP together with cAMP-analogs that activate Type II PKA increased P-STAR and further increased steroidogenesis. Our results suggest that VIP-induced STAR expression and function in granulosa cells result from the preferential activation of Type I PKA. Furthermore, the PKA and PKC pathways appear to converge at regulating VIP-mediated Star transcription and translation.
Kowalewski
Mariusz P
MP
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, United States.
Dyson
Matthew T
MT
Boos
Alois
A
Stocco
Douglas M
DM
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; D014660:Vasoactive Intestinal Peptide; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C