Decidual activin: its role in the apoptotic process and its regulation by prolactin.
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.
Tessier
Christian
C
Department of Physiology and Biophysics, University of Illinois, Chicago 60612-7432, USA.
Prigent-Tessier
Anne
A
Bao
Lei
L
Telleria
Carlos M
CM
Ferguson-Gottschall
Susan
S
Gibori
Gil B
GB
Gu
Yan
Y
Bowen-Shauver
Jennifer M
JM
Horseman
Nelson D
ND
Gibori
Geula
G
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
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