Growth Hormone (GH) or Insulin-like Growth Factor (IGF)-I Represses 11.BETA.-Hydroxysteroid Dehydrogenase Type 1 (HSD1) mRNA Expression in 3T3-L1 Cells and Its Activity in Their Homogenates

Abstract

Abstract.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. 11β-hydroxysteroid dehydrogenase type 1 (11β-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 11β-HSD1 in 3T3-L1 cell homogenates and its mRNA expression. First, we showed that 11β-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 11β-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, 11β-HSD1 mRNA levels were decreased compared with basal levels. IGF-I treatment of adipocytes resulted in rapid decreases in 11β-HSD1 activity as well as mRNA levels; however, IGF-I treatment for 24 h increased 11β-HSD1 activity. In long-term cultured adipocytes, GH or IGF-I showed only inhibitory effects on 11β-HSD1 activity. In conclusion, 11β-HSD1 activity was suppressed by GH or IGF-I in differentiated adipocytes, probably due to a reduction of 11β-HSD1 mRNA levels. These data suggest that under the conditions of low GH or IGF-I concentrations, 11β-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 11β-HSD1 activity.

Mechanism of repression of 11β-hydroxysteroid dehydrogenase type 1 by growth hormone in 3T3-L1 adipocytes

“…Due to these increased levels, we decided to use fully differentiated adipocytes on the tenth day after induction of differentiation for our experiments. Levels of 11β-HSD1 mRNA were decreased by GH and IGF-I in these fully differentiated adipocytes as we previously reported [8]. The repression of 11β-HSD1 mRNA by IGF-I treatment was partially restored by linsitinib.…”

“…Our previous study also indicated that 11β-HSD1 activity and messenger ribonucleic acid (mRNA) expression were suppressed by both GH and insulin-like growth factor (IGF)-I in 3T3-L1 adipocytes [8]. These findings suggest that lack of GH and IGF-I may cause activation of 11β-HSD1 in patients with adult GH deficiency, and induce metabolic disorders related to insulin resistance.…”

“…In rodent adipose tissue, mRNA [8]. In this study, to further elucidate the mechanisms of 11β-HSD1 regulation by GH, we investigated whether GH regulates 11β-HSD1 activity directly or indirectly via locally produced IGF-I using the IGF-I receptor inhibitor linsitinib.…”

Expression of microRNA-26b, an obesity-related microRNA, is regulated by free fatty acids, glucose, dexamethasone and growth hormone in human adipocytes

“…As energy-source materials, free fatty acids (FFAs) and glucose are important in obesity and obesity-related insulin sensitivity. Furthermore, studies have indicated that glucocorticoids and growth hormone (GH) are also closely associated with obesity and insulin resistance (6,7). However, the molecular mechanisms underlying the effects of FFAs, glucose, glucocorticoids and GH in obesity and insulin sensitivity, have not yet been fully clarified.…”

The Intricate Role of Growth Hormone in Metabolism

“…Recent studies have shown that GH down-regulates 11βHSD1 (11β-hydroxysteroid dehydrogenase type 1) expression in the adipose tissue (Morita et al, 2009; Zhao et al, 2011). 11βHSD1 amplifies glucocorticoid action by stimulating the conversion of inactive dehydrocorticosterone to active corticosterone.…”