title: Decidual activin: its role in the apoptotic process and its regulation by prolactin.
abstract: Successful pregnancy requires profound differentiation and reorganization of the uterine tissues including, as pregnancy progresses, extensive apoptosis of decidual tissue to accommodate the developing conceptus. We have previously shown a positive correlation between expression of activin A and apoptosis in the decidua and have also shown that expression of activin A occurs at the time when prolactin (PRL) receptors disappear from decidual cells. The goals of this study were to examine whether activin A plays a role in decidual apoptosis and whether expression of activin A in the decidua is regulated by PRL and placental lactogens. Studies were carried out using primary rat decidual cells, a decidual cell line (GG-AD), and PRL null mice. Treatment of decidual cells with activin A significantly increased DNA degradation, caspase 3 activity, and caspase 3 mRNA expression. However, this effect was observed only in the absence of endogenous activin production by these cells. Addition of follistatin to decidual cells that were producing activin A decreased both caspase 3 activity and mRNA expression. Similarly, addition of activin-blocking antibodies to cultures of GG-AD cells, which also produce activin A, caused a reduction in both DNA degradation and caspase 3 activity. PRL and placental lactogens caused an inhibition of activin A mRNA expression in primary decidual cells. Even more convincingly, decidua of PRL null mice expressed abundant activin A at a time when no expression of this hormone is detected in wild-type mice and treatment of PRL null mice with PRL caused a profound inhibition of activin A mRNA expression. In summary, our investigations into the role and regulation of decidual activin have revealed that activin A can induce cell death in the decidua and that its expression is under tight regulation by PRL and placental lactogens.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois, Chicago 60612-7432, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Tessier
authors.forename: Anne
authors.initials: A
authors.lastname: Prigent-Tessier
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Telleria
authors.forename: Susan
authors.initials: S
authors.lastname: Ferguson-Gottschall
authors.forename: Gil B
authors.initials: GB
authors.lastname: Gibori
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bowen-Shauver
authors.forename: Nelson D
authors.initials: ND
authors.lastname: Horseman
authors.forename: Geula
authors.initials: G
authors.lastname: Gibori
mesh_terms: D028341:Activins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002460:Cell Line; D002478:Cells, Cultured; D053938:DNA Fragmentation; D017931:DNA Primers / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010928:Placental Lactogen / Q000494:pharmacology; D011388:Prolactin / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000502:physiology
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D028341:Activins; D011388:Prolactin; D010928:Placental Lactogen; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases