Impairment of adenylate cyclase activity and G-proteins in human uterine leiomyoma.
The mechanisms responsible for the growth of uterine leiomyoma (a frequent cause of infertility in women) are largely unknown. Some data supports that cAMP plays a role in the growth of uterine cells but there are no reports on the status of the cAMP producing system in this human benign neoplasia. In this study, biopsies from leiomyoma and the adjacent myometrium were taken from menstruating women subjected to total hysterectomy for leiomyoma. Adenylate cyclase activity was determined by a protein-binding method, and the expression of alpha(s), alphai1/2, alphai3 and alphai0) G-protein subunits was analysed by immunoblot. The leiomyoma samples exhibited a decreased expression of as and ai1/2 with respect to the adjacent myometrial tissue. No differences were observed in alphai3 and alphaio protein expression. The basal adenylate cyclase activity as well as the efficacy (as assessed by the maximal stimulation levels) of either forskolin or, to a lesser extent, Gpp[NH]p on stimulation the enzyme activity was significantly lower in leiomyoma than in myometrium, whereas the potency (as assessed by the ED50 values) of these two agents did not vary. Present data indicate that the human leiomyoma is associated with low levels of cAMP. It is conceivable that the loss of sensitivity of adenylate cyclase to endogenous regulatory molecules could be related to the pathogenesis of human leiomyomas given that cAMP inhibits the MAP-kinase cascade in uterine tissues.
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Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares, Spain.
Carrero
I
I
Hrïstov
R L
RL
Valenzuela
P
P
Martínez
P
P
Cortés
J
J
Prieto
J C
JC
Guijarro
L G
LG
D000067956:Adenylyl Cyclase Inhibitors; D000328:Adult; D001706:Biopsy; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007044:Hysterectomy; D015151:Immunoblotting; D007889:Leiomyoma / Q000201:enzymology* / Q000378:metabolism*; D008875:Middle Aged; D009215:Myometrium / Q000201:enzymology / Q000378:metabolism; D014594:Uterine Neoplasms / Q000201:enzymology* / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D005576:Colforsin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins