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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1507/endocrj.k08e-311 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.
Clin Pharmacol Drug Dev
January 2025
Actinogen Medical Ltd, Sydney, New South Wales, Australia.
This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.
View Article and Find Full Text PDFElectrospun 11β-HSD1 Inhibitor-Loaded Scaffolds for Accelerating Diabetic Ulcer Healing.
ACS Appl Bio Mater
December 2024
Jiangsu Provincial Engineering Research Centre of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Diabetic ulcers (DUs) are a common and severe complication of diabetes, characterized by impaired wound healing due to a complex pathophysiological mechanism. Elevated levels of 11β-hydroxysteroid dehydrogenase type I (11β-HSD1) in wounds have been demonstrated to modulate glucocorticoid activity, leading to delayed skin cell proliferation and restricted angiogenesis, ultimately hindering wound healing. In this study, we propose an electrospun poly(ε-caprolactone) (PCL) nanofiber scaffold doped with the 11β-HSD1 inhibitor BVT2733 (BPs) to prevent 11β-HSD1 activity during the diabetic wound healing process.
View Article and Find Full Text PDFBlockade of 11β-hydroxysteroid dehydrogenase type 1 ameliorates metabolic dysfunction-associated steatotic liver disease and fibrosis.
Heliyon
October 2024
College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, 28160, South Korea.
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key enzyme involved in the conversion of cortisone to active cortisol in the liver. Elevated cortisol levels can trigger oxidative stress, inflammation, and hepatocyte damage, highlighting the importance of 11β-HSD1 inhibition as a potential therapeutic approach. This study aimed to explore the effects of INU-101, an inhibitor of 11β-HSD1, on the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis.
View Article and Find Full Text PDFGlycyrrhizic acid and patchouli alcohol in Huoxiang Zhengqi attenuate intestinal inflammation and barrier injury via regulating endogenous corticosterone metabolism mediated by 11β-HSD1.
J Ethnopharmacol
February 2025
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:
Ethnopharmacological Relevance: Ulcerative colitis (UC), a chronic inflammatory bowel disease, has become a significant public health challenge due to the limited effectiveness of available therapies. Huoxiang Zhengqi (HXZQ), a well-established traditional Chinese formula, shows potential in managing UC, as suggested by clinical and pharmacological studies. However, the active components and mechanisms responsible for its effects remain unclear.
View Article and Find Full Text PDFSynthesis of Carborane-Thiazole Conjugates as Tyrosinase and 11β-Hydroxysteroid Dehydrogenase Inhibitors: Antiproliferative Activity and Molecular Docking Studies.
Molecules
October 2024
Department of Chemical Technology and Pharmaceuticals, Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University, Jurasza 2, 85-089 Bydgoszcz, Poland.
The presented study depicts the synthesis of 11 carborane-thiazole conjugates with anticancer activity, as well as an evaluation of their biological activity as inhibitors of two enzymes: tyrosinase and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The overexpression of tyrosinase results in the intracellular accumulation of melanin and can be observed in melanoma. The overexpression of 11β-HSD1 results in an elevation of glucocorticoid levels and has been associated with the aggravation of metabolic disorders such as type II diabetes mellitus and obesity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!