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 tak
en from menstruating women subjected to total hysterectomy for leiomyoma, A
denylate cyclase activity was determined by a protein-binding method, and t
he expression of alpha (s), alpha (i1/2), alpha (i3) and alpha (i0)) G-prot
ein subunits was analysed by immunoblot. The leiomyoma samples exhibited a
decreased expression of a(s) and a(i1/2) with respect to the adjacent myome
trial tissue. No differences were observed in alpha (i3) and alpha (i0) pro
tein expression. The basal adenylate cyclase activity as well as the effica
cy las assessed by the maximal stimulation levels) of either forskolin or,
to a lesser extent, Gpp[NH]p on stimulation the enzyme activity was signifi
cantly lower in leiomyoma than in myometrium, whereas the potency (as asses
sed by the ED50 values) of these two agents did not vary. Present data indi
cate 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 leiomyo
mas given that cAMP inhibits the MAP-kinase cascade in uterine tissues. (C)
2000 Harcourt Publishers Ltd.