Insulin receptor tyrosine kinase activity and substrate 1 (IRS-1) expression in human myometrium and leiomyoma.
BACKGROUND
Uterine leiomyomas are the commonest tumors of the genital tract. Growth factors seem to be implicated in the development of leiomyoma.


OBJECTIVE
To determine the insulin receptor (IR) tyrosine kinase activity--phosphorylation of exogenous substrate poly(Glu 4: Tyr 1)--and insulin receptor substrate 1 expression in normal myometrium and leiomyoma.


METHODS
The study group consisted of 12 women with leiomyoma undergoing routine hysterectomy. Samples of leiomyoma and adjacent normal myometrium were obtained at the time of operation. Plasma membrane fractions were prepared and samples were incubated with and without insulin and incubated with exogenous substrate poly(Glu 4: Tyr 1). IRS-1 expression was studied in the whole lysate via Western blotting using specific antibodies. Data were analyzed using Student's t-test.


RESULTS
The phosphorylation of the exogenous substrate poly(Glu 4: Tyr 1) in myometrium (1.566+/-0.177) and in leiomyoma (1.98+/-0.612) were similar (P=0.774). The IRS-1 levels in myometrium (0.190+/-0.022) and in leiomyoma (0.226+/-0.022) were not different (P=0.184).


CONCLUSIONS
There was no difference in IR tyrosine kinase activity (phosphorylation of exogenous substrate) and IRS-1 expression between normal myometrium and leiomyomata. Other steps in the insulin signaling cascade require further study to investigate the role of insulin receptor in leiomyomata.
Orcy
Rafael B
RB
Department of Physiology, Núcleo Gerar de Reprodução Humana, Hospital Moinhos de Vento, Porto Alegre, Brazil.
Brum
Ilma
I
da Silva
Roselis S M
RS
Kucharski
Luiz C R
LC
Corleta
Helena v E
Hv
Capp
Edison
E
D000818:Animals; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007889:Leiomyoma / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014594:Uterine Neoplasms / Q000378:metabolism*
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; C410467:insulin receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases