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Cited by 129Estrogen and related hormone effectsNeuroendocrine regulation and behaviorReceptor Mechanisms and Signaling

Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus

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Nissenson, R., Flouret, G., Hechter, O.·1978·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.75.4.2044PMC PMC392480
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Abstract

Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the "estrogen-dominated" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In "progesterone-dominated" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [(3)H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [(3)H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [(3)H]oxytocin binding; the concentration of specific [(3)H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon the continuous de novo synthesis of oxytocin receptors. In contrast, progesterone, like actinomycin D, appears to act at the nuclear locus to repress synthesis of oxytocin receptors.

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Authors
Nissenson, R., Flouret, G., & Hechter, O.
Affiliations
Northwestern University (US)
ORCID
Nissenson, R.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1978-04
Volume
75
Issue
4
Pages
2044-2048
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.75.4.2044
PMC
PMC392480
OpenAlex
W2048909189
Cited by
129
References
21
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 2
FWCI
4.78
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
oxytocin receptor, estradiol, progesterone, uterine contractility, myometrium, receptor density, receptor synthesis, actinomycin D, rabbit uterus
MeSH terms
Animals, Estradiol, Female, Kinetics, Membranes, Methacholine Compounds, Microsomes, Oxytocin, Progesterone, Rabbits, Receptors, Cell Surface, Uterine Contraction, Uterus

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