Progesterone receptor localization and isoforms in myometrium, decidua, and fetal membranes from rhesus macaques: evidence for functional progesterone withdrawal at parturition.
OBJECTIVE
It is not known whether withdrawal of progesterone (P) action is a prerequisite for parturition in women or in nonhuman primates because concentrations of circulating progesterone or progesterone receptors (PR) in myometrium and decidua do not decrease before delivery. To examine this potentially important regulatory mechanism, we determined PR isoforms, PR localization, and mRNA in myometrium, decidua, and fetal membranes from rhesus monkeys during pregnancy and in spontaneous labor at term.


METHODS
Gestational tissues were obtained midpregnancy (day 80-100), late pregnancy (day 130-145), and during spontaneous labor at term (day 161-167). Samples of rhesus monkey myometrium, decidua, chorion-decidua, and amnion were collected and analyzed for total nuclear and cytosolic PR by competitive binding assay. Progesterone receptor isoforms were identified and quantified by Western blot analysis, and PR mRNA was determined by a specific ribonuclease protection assay. Nuclear PR was localized by immunohistochemistry with monoclonal anti-PR (JZB39) after microwave stabilization.


RESULTS
Myometrium and decidua showed no change in total PR during pregnancy and labor. Nuclear PR was not detected in fetal membranes by binding assay but was localized in amnion epithelial and mesenchymal cells and in chorion laeve cytotrophoblasts by immunohistochemistry. Staining for PR was substantially less by serial antibody dilution in fetal membranes than in decidua. Message for PR was confirmed in all tissues analyzed. A significant (P <.05) shift in the ratio of PR isoforms (from PR-B dominance at midpregnancy to PR-A dominance in labor) was observed in myometrium but not in decidua. Both PR-A and PR-B isoforms and PR nuclear staining were nearly undetectable in amnion obtained during labor.


CONCLUSIONS
A shift to PR-A dominance in myometrium at term together with a loss of PR in fetal membranes provides evidence for a functional progesterone withdrawal mechanism, which may facilitate the initiation of parturition in primates.
Haluska
G J
GJ
Division of Reproductive Sciences, Oregon Regional Primate Research Center/Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006-3499, USA.
Wells
T R
TR
Hirst
J J
JJ
Brenner
R M
RM
Sadowsky
D W
DW
Novy
M J
MJ
D000818:Animals; D003656:Decidua / Q000166:cytology*; D005321:Extraembryonic Membranes / Q000166:cytology*; D005260:Female; D007150:Immunohistochemistry; D007743:Labor, Obstetric / Q000502:physiology*; D008253:Macaca mulatta; D009215:Myometrium / Q000166:cytology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011374:Progesterone / Q000502:physiology*; D020033:Protein Isoforms / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis* / Q000737:chemistry
D020033:Protein Isoforms; D011980:Receptors, Progesterone; D011374:Progesterone