Progesterone withdrawal, and not increased circulating relaxin, mediates the decrease in myometrial relaxin receptor...

Area of Science:

• Reproductive Biology
• Endocrinology
• Molecular Biology

Background:

• Myometrial relaxin family peptide receptor 1 (RXFP1) expression decreases in late gestation and labor in pregnant rats.
• This decrease coincides with high circulating relaxin and low progesterone levels, suggesting a functional relaxin withdrawal.
• The regulatory roles of circulating relaxin and progesterone on myometrial RXFP1 remain unclear.

Purpose of the Study:

• To investigate the regulatory role of progesterone and circulating relaxin on myometrial RXFP1 expression in pregnant rats.
• To examine the effects of antiprogestin RU486 and anti-rat relaxin antibody (MCA1) on RXFP1 and related gene expression.

Main Methods:

• Pregnant rats were treated with RU486 (antiprogestin) on gestational days (GD) 7, 16, or 19.
• Pregnant rats received intravenous administration of MCA1 (anti-rat relaxin antibody) from GD 17 to GD 19.
• Myometrial RXFP1, Esr1, Esr2, Vegf, and plasma hormone levels were analyzed in treated and control rats.

Main Results:

• RU486 treatment significantly reduced myometrial RXFP1 expression, increased plasma progesterone and 17beta-estradiol, and altered myometrial Esr1 and Esr2 levels.
• MCA1 treatment did not significantly affect myometrial RXFP1, Esr1, or Esr2 expression but reduced myometrial Vegf.
• RU486-induced decrease in RXFP1 was associated with increased 17beta-estradiol and myometrial Esr1.

Conclusions:

• Myometrial RXFP1 expression in pregnant rats is primarily mediated by progesterone, not circulating relaxin.
• Blocking progesterone action with RU486 leads to decreased RXFP1 expression, potentially via increased 17beta-estradiol and Esr1.
• These findings clarify the hormonal regulation of RXFP1 and its implications for myometrial function during pregnancy and labor.