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Progesterone Receptor Localization and Isoforms in Myometrium, Decidua, and Fetal Membranes From Rhesus Macaques: Evidence for Function Progresterone Withdrawal at Parturtion

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Abstract

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.

Conclusion

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.

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Authors and Affiliations

  1. Division of Reproductive Sciences, Oregon Regional Primate Research Center/Oregon Health & Science University, 505 NW 185th Avenue, 97006-3499, Beaverton, Oregon, USA

    G. J. Haluska PhD, T. R. Wells BS, J. J. Hirst PhD, R. M. Brenner PhD, D. W. Sadowsky PhD & Miles J. Novy MD

  2. Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon, USA

    G. J. Haluska PhD, T. R. Wells BS, J. J. Hirst PhD, R. M. Brenner PhD, D. W. Sadowsky PhD & Miles J. Novy MD

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  1. G. J. Haluska PhD
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  2. T. R. Wells BS
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  3. J. J. Hirst PhD
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  4. R. M. Brenner PhD
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  5. D. W. Sadowsky PhD
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  6. Miles J. Novy MD
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Corresponding author

Correspondence to Miles J. Novy MD.

Additional information

Supported by NIH grants HD06159 (to MJN), HD19182 (to RMB), RR00163, and HD18185.

We gratefully acknowledge the expert assistance of Noreen Currier, Kunie Mah, and Michael Cook in carrying out this work. We thank Dr. Geoffrey Greene, University of Chicago, for the JZB39 antibody.

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Haluska, G.J., Wells, T.R., Hirst, J.J. et al. Progesterone Receptor Localization and Isoforms in Myometrium, Decidua, and Fetal Membranes From Rhesus Macaques: Evidence for Function Progresterone Withdrawal at Parturtion. Reprod. Sci. 9, 125–136 (2002). https://doi.org/10.1177/107155760200900303

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