Activin-A in myometrium: characterization of the actions on myometrial cells.
Activin is a pleiotropic growth factor with a broad pattern of tissue distribution that includes reproductive tissues. Although direct actions of activin have been described in gonadal and uterine tissues, actions in the myometrium have not been defined. In this study we have characterized the responsiveness of uterine tissue and myometrial cell lines to activin-A. Uterine tissue and two myometrial cell lines, PHM1 (pregnant human myometrial 1) and hTERT HM (telomerase reverse transcriptase-infected human myometrial) respond to activin-A as measured by phosphorylation of Smad-2. Those cell lines express a full complement of activin receptors, as well as activin beta(A) subunit and follistatin. Activin inhibited proliferation of PHM1 and human telomerase reverse transcriptase-infected human myometrial cell line cells, with more extensive growth inhibition observed in PHM1s. In PHM1s, activin-A decreased oxytocin receptor and HoxA-10 mRNA expression but did not alter total progesterone receptor, cyclooxygenase-2 (Cox-2), and connexin 43 mRNA expression levels. Furthermore, treatment of PHM1 myometrial cells with activin-A attenuated oxytocin and thromboxaneA2 induced intracellular Ca(2+) accumulation. In conclusion, myometrial cells are activin sensitive, and activin-A can regulate myometrial cell functions.
Ciarmela
Pasquapina
P
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Wiater
Ezra
E
Vale
Wylie
W
D028341:Activins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D009215:Myometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects* / Q000378:metabolism
D018031:Connexin 43; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D011980:Receptors, Progesterone; C422405:activin A; D028341:Activins; C092119:Hoxa10 protein, mouse; D010121:Oxytocin; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D002118:Calcium