Document Detail


Growth hormone (GH) or insulin-like growth factor (IGF)-I represses 11beta-hydroxysteroid dehydrogenase type 1 (HSD1) mRNA expression in 3T3-L1 cells and its activity in their homogenates.
MedLine Citation:
PMID:  19352050     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with growth hormone (GH) deficiency (GHD) have a clinical feature of visceral adiposity and it has been reported that these patients have an increased active cortisol (F)/inactive cortisone (E) metabolite ratio. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an enzyme expressed in liver and adipose tissue that acts principally as a reductase converting E to F. In the present study, we investigated the effects of GH or IGF-I on the activity of 11beta- HSD1 in 3T3-L1 cell homogenates and its mRNA expression. First, we showed that 11beta-HSD1 activity and mRNA levels were low in preadipocytes and increased throughout the process of adipogenesis. When fully differentiated adipocytes were treated with GH for various times, the activity of 11beta-HSD1 was significantly decreased after 4 h and 8 h but was restored to basal levels after 24 h. After 8 h of GH stimulation, 11beta-HSD1 mRNA levels were decreased compared with basal levels. IGF-I treatment of adipocytes resulted in rapid decreases in 11beta-HSD1 activity as well as mRNA levels; however, IGF-I treatment for 24 h increased 11beta-HSD1 activity. In long-term cultured adipocytes, GH or IGF-I showed only inhibitory effects on 11beta-HSD1 activity. In conclusion, 11beta-HSD1 activity was suppressed by GH or IGF-I in differentiated adipocytes, probably due to a reduction of 11beta-HSD1 mRNA levels. These data suggest that under the conditions of low GH or IGF-I concentrations, 11beta-HSD1 activity in adipose tissue is maintained at high levels, leading to an increase in active cortisol that induces adipogenesis and/or lipogenesis. Thus, visceral adiposity in patients with GHD might be related to increased 11beta-HSD1 activity.
Authors:
Junko Morita; Fumihiko Hakuno; Naomi Hizuka; Shin-Ichiro Takahashi; Kazue Takano
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-07
Journal Detail:
Title:  Endocrine journal     Volume:  56     ISSN:  1348-4540     ISO Abbreviation:  Endocr. J.     Publication Date:  2009  
Date Detail:
Created Date:  2009-07-31     Completed Date:  2009-10-26     Revised Date:  2011-06-16    
Medline Journal Info:
Nlm Unique ID:  9313485     Medline TA:  Endocr J     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  561-70     Citation Subset:  IM    
Affiliation:
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*,  biosynthesis
11-beta-Hydroxysteroid Dehydrogenase Type 2 / metabolism
3T3-L1 Cells
Adipocytes / metabolism
Animals
Cell Differentiation
Growth Hormone / physiology*
Humans
Insulin-Like Growth Factor I / physiology*
Mice
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/RNA, Messenger; 67763-96-6/Insulin-Like Growth Factor I; 9002-72-6/Growth Hormone; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 1; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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