Steroidogenic Acute Regulatory (StAR) Protein and Cholesterol Side-Chain Cleavage (P450scc) as Molecular and Cellular Targets for 17α-Ethynylestradiol in Salmon Previtellogenic Oocytes

2007 ◽  
Vol 20 (12) ◽  
pp. 1811-1819 ◽  
Author(s):  
Siv-Hege Vang ◽  
Trond M. Kortner ◽  
Augustine Arukwe
Keyword(s):  
Side Chain ◽  
Cellular Targets ◽  
Side Chain Cleavage ◽  
Star Protein ◽  
Chain Cleavage ◽  
Steroidogenic Acute Regulatory

scholarly journals Salt-Inducible Kinase Is Involved in the ACTH/cAMP-Dependent Protein Kinase Signaling in Y1 Mouse Adrenocortical Tumor Cells

2001 ◽  
Vol 15 (8) ◽  
pp. 1264-1276 ◽  
Author(s):  
Xing-zi Lin ◽  
Hiroshi Takemori ◽  
Yoshiko Katoh ◽  
Junko Doi ◽  
Nanao Horike ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Promoter Activity ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Side Chain ◽  
Mrna Levels ◽  
Steroidogenic Factor 1 ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Steroidogenic Acute Regulatory

Abstract The involvement of salt-inducible kinase, a recently cloned protein serine/threonine kinase, in adrenal steroidogenesis was investigated. When Y1 mouse adrenocortical tumor cells were stimulated by ACTH, the cellular content of salt-inducible kinase mRNA, protein, and enzyme activity changed rapidly. Its level reached the highest point in 1–2 h and returned to the initial level after 8 h. The mRNA levels of cholesterol side-chain cleavage cytochrome P450 and steroidogenic acute regulatory protein, on the other hand, began to rise after a few hours, reaching the highest levels after 8 h. The salt-inducible kinase mRNA level in ACTH-, forskolin-, or 8-bromo-cAMP-treated Kin-7 cells, mutant Y1 with less cAMP-dependent PKA activity, remained low. However, Kin-7 cells, when transfected with a PKA expression vector, expressed salt-inducible kinase mRNA. Y1 cells that overexpressed salt-inducible kinase were isolated, and the mRNA levels of steroidogenic genes in these cells were compared with those in the parent Y1. The level of cholesterol side-chain cleavage cytochrome P450 mRNA in the salt-inducible kinase-overexpressing cells was markedly low compared with that in the parent, while the levels of Ad4BP/steroidogenic factor-1-, ACTH receptor-, and steroidogenic acute regulatory protein-mRNAs in the former were similar to those in the latter. The ACTH-dependent expression of cholesterol side-chain cleavage cytochrome P450- and steroidogenic acute regulatory protein-mRNAs in the salt-inducible kinase-overexpressing cells was significantly repressed. The promoter activity of the cholesterol side-chain cleavage cytochrome P450 gene was assayed by using Y1 cells transfected with a human cholesterol side-chain cleavage cytochrome P450 promoter-linked reporter gene. Addition of forskolin to the culture medium enhanced the cholesterol side-chain cleavage cytochrome P450 promoter activity, but the forskolin-dependently activated promoter activity was inhibited when the cells were transfected with a salt-inducible kinase expression vector. This inhibition did not occur when the cells were transfected with a salt-inducible kinase (K56M) vector that encoded an inactive kinase. The salt-inducible kinase’s inhibitory effect was also observed when nonsteroidogenic, nonAd4BP/steroidogenic factor-1 -expressing, NIH3T3 cells were used for the promoter assays. These results suggested that salt-inducible kinase might play an important role(s) in the cAMP-dependent, but Ad4BP/steroidogenic factor-1-independent, gene expression of cholesterol side-chain cleavage cytochrome P450 in adrenocortical cells.

scholarly journals The role of the StAR protein in steroidogenesis: challenges for the future

2000 ◽  
Vol 164 (3) ◽  
pp. 247-253 ◽  
Author(s):  
DM Stocco
Keyword(s):  
Side Chain ◽  
Inner Mitochondrial Membrane ◽  
Star Protein ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Hormone Biosynthesis ◽  
Steroidogenic Acute Regulatory ◽  
The Brain ◽  
Star Gene

The steroidogenic acute regulatory or StAR protein has been shown to be instrumental in the acute regulation of steroid hormone biosynthesis through its action in mediating cholesterol transfer to the inner mitochondrial membrane and the cholesterol side chain cleavage enzyme system. Since the time of its cloning in 1994, a number of studies have been performed which underscore the important role that this protein plays in steroidogenesis. While it is now quite apparent that StAR fulfills the criteria for the acute regulator as proposed by early studies, several crucial areas remain poorly understood. This list is topped by the so far intractable nature of the mechanism of action of StAR in transferring cholesterol to the P450scc enzyme. A second area which should prove to be of great interest is that of further understanding the regulation of the StAR gene which, like many genes, is quite complex. Lastly, with the recent demonstration of StAR being present in the brain, determining if StAR has a role in the synthesis of neurosteroids should prove to be of great importance.

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