Effect of adrenocorticotropic hormone on UCP1 gene expression in brown adipocytes

Like other tissues, adrenocorticotropic hormone (ACTH) can produce its effect on brown adipose tissue (BAT). This study was taken to understand the direct effect of ACTH action on thermogenin gene expression and possible relation with α receptors and caffeine with this hormone.

Brown fat precursor cells were isolated from interscapular BAT of young mice and grown in culture. The cells were exposed to norepinephrine (NE) and other agents. Total RNA was isolated after harvesting the cells, and northern blot analysis was performed. Hybridization was performed with nick translated cDNA probes. Filters were exposed to film, and results were evaluated by scanning. Cyclic adenosine monophosphate (cAMP) was measured by using Amersham assay kit.

ACTH stimulates thermogenin gene expression in brown adipocytes. Initiation and maximum stimulations are observed with 0.01 μM and 10 μM (about 45%) of ACTH, respectively, in comparison to 0.1 μM of NE. Maximum response of cAMP is also observed with 10 μM of ACTH (about 64%). Studies with cirazoline and ACTH show that UCP1 mRNA expression is increased significantly with 10 μM of ACTH, whereas cAMP generation is decreased. In the presence of caffeine, ACTH increases cAMP generation and UCP1 gene expression more than twofold.

ACTH stimulates thermogenin gene expression in cultured brown adipocytes. The complex interrelationship of ACTH with cirazoline indicates the possibility of relation between the activity of ACTH and α receptors in brown adipocytes. Further stimulation of cAMP generation and thermogenin gene expression is possible with ACTH in conjugation with caffeine and RO 20-1724.