Steroidogenic abnormalities in translocator protein knockout mice and significance in the aging male

2018 ◽  
Vol 475 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Anna M. Barron ◽  
Bin Ji ◽  
Seiji Kito ◽  
Tetsuya Suhara ◽  
Makoto Higuchi

The translocator protein (TSPO) has been proposed to act as a key component in a complex important for mitochondrial cholesterol importation, which is the rate-limiting step in steroid hormone synthesis. However, TSPO function in steroidogenesis has recently been challenged by the development of TSPO knockout (TSPO-KO) mice, as they exhibit normal baseline gonadal testosterone and adrenal corticosteroid production. Here, we demonstrate that despite normal androgen levels in young male TSPO-KO mice, TSPO deficiency alters steroidogenic flux and results in reduced total steroidogenic output. Specific reductions in the levels of progesterone and corticosterone as well as age-dependent androgen deficiency were observed in both young and aged male TSPO-KO mice. Collectively, these findings indicate that while TSPO is not critical for achieving baseline testicular and adrenal steroidogenesis, either indirect effects of TSPO on steroidogenic processes, or compensatory mechanisms and functional redundancy, lead to subtle steroidogenic abnormalities which become exacerbated with aging.

1974 ◽  
Vol 44 (1) ◽  
pp. 243-250 ◽  
Author(s):  
Friedrich W. Kahnt ◽  
Alfred Milani ◽  
Hans Steffen ◽  
Robert Neher

1978 ◽  
Vol 39 (02) ◽  
pp. 496-503 ◽  
Author(s):  
P A D’Amore ◽  
H B Hechtman ◽  
D Shepro

SummaryOrnithine decarboxylase (ODC) activity, the rate-limiting step in the synthesis of polyamines, can be demonstrated in cultured, bovine, aortic endothelial cells (EC). Serum, serotonin and thrombin produce a rise in ODC activity. The serotonin-induced ODC activity is significantly blocked by imipramine (10-5 M) or Lilly 11 0140 (10-6M). Preincubation of EC with these blockers together almost completely depresses the 5-HT-stimulated ODC activity. These observations suggest a manner by which platelets may maintain EC structural and metabolic soundness.


Diabetes ◽  
1993 ◽  
Vol 42 (2) ◽  
pp. 296-306 ◽  
Author(s):  
D. C. Bradley ◽  
R. A. Poulin ◽  
R. N. Bergman

1979 ◽  
Vol 44 (3) ◽  
pp. 912-917 ◽  
Author(s):  
Vladimír Macháček ◽  
Said A. El-bahai ◽  
Vojeslav Štěrba

Kinetics of formation of 2-imino-4-thiazolidone from S-ethoxycarbonylmethylisothiouronium chloride has been studied in aqueous buffers and dilute hydrochloric acid. The reaction is subject to general base catalysis, the β value being 0.65. Its rate limiting step consists in acid-catalyzed splitting off of ethoxide ion from dipolar tetrahedral intermediate. At pH < 2 formation of this intermediate becomes rate-limiting; rate constant of its formation is 2 . 104 s-1.


1991 ◽  
Vol 56 (8) ◽  
pp. 1701-1710 ◽  
Author(s):  
Jaromír Kaválek ◽  
Vladimír Macháček ◽  
Miloš Sedlák ◽  
Vojeslav Štěrba

The cyclization kinetics of N-(2-methylcarbonylphenyl)-N’-methylsulfonamide (IIb) into 3-methyl-(1H)-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide (Ib) has been studied in ethanolamine, morpholine, and butylamine buffers and in potassium hydroxide solution. The cyclization is subject to general base and general acid catalysis. The value of the Bronsted coefficient β is about 0.1, which indicates that splitting off of the proton from negatively charged tetrahedral intermediate represents the rate-limiting and thermodynamically favourable step. In the solutions of potassium hydroxide the cyclization of dianion of the starting ester IIb probably becomes the rate-limiting step.


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