Changes in beta(2)-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas.
Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of alpha(2)- and beta(2)-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the alpha(2)/beta(2)-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in beta(2)-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be approximately 50% lower, whereas the phosphodiesterase activity was significantly increased (by approximately 100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through beta(2)-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.
Adolfsson
P I
PI
Division of Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Sweden. per.adolfsson@far.liu.se
Haug
I
I
Berg
G
G
Svensson
S P
SP
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D008715:Methionine / Q000378:metabolism; D008875:Middle Aged; D009215:Myometrium / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000096:biosynthesis; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis*; D013462:Sulfur Radioisotopes / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; D013462:Sulfur Radioisotopes; D014316:Tritium; D008715:Methionine; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D013936:Thymidine