Molecular Human Reproduction, Vol. 6, No. 9, 835-842,
September 2000
© 2000 European Society of Human Reproduction and Embryology
Uterine physiology |
Changes in ß2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas
1 Division of Pharmacology, Department of Medicine and Care, 2 Division of Cell Biology, Department of Biology and Surgery and 3 Division of Obstetrics and Gynecology, Department of Health and Environment, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden
Abstract
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
2- and ß2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the
2/ß2-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in ß2-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 ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through ß2-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.
adenylyl cyclase/adrenergic receptors/cAMP/leiomyoma/phosphodiesterase
Notes
4 To whom correspondence should be addressed at: Division of Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. E-mail: per.adolfsson{at}far.liu.se
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