Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharide.

Abstract

AIM:

To evaluate the effect of progesterone on interleukin (IL)-6, prostaglandin (PG) E2 and nitric oxide (NO) metabolite (NOx) production and contractile activity by NO in pregnant mice treated with lipopolysaccharide (LPS).

METHODS:

Pregnant C57BL mice on day 14 of gestation were killed 6 h after i.p. injection of LPS (400 microg/kg) or vehicle. Progesterone (2 mg) was subcutaneously injected 2 h before LPS treatment. Uterine rings were equilibrated in Krebs-Henseleit solution (37 degrees C) bubbled with 20% O2 and 5% CO2 (pH 7.4) for sampling and isometric tension recording. IL-6, PGE2 and NOx productions were measured from the bathing solution. Changes in spontaneous contractile activity in response to cumulative concentrations of l-arginine, diethylamine/nitric oxide (DEA/NO, the NO donor), and 8-bromo-cGMP (8-br-cGMP) were compared. Integral contractile activity over 10 min after each concentration was calculated and expressed as percentage change from basal activity. Statistical analyses were performed using one-way anova followed by Dunnett's test (significance was defined as P < 0.05).

RESULTS:

Interleukin-6 (34.7 +/- 6.0 pg/g tissue), PGE2 (66.8 +/- 6.7 pg/g tissue) and NOx (51.0 +/- 5.4 pmol/2 mL/g wet tissue) production were significantly stimulated by LPS treatment (138.2 +/- 23.2, 147.0 +/- 29.0, 98.6 +/- 16.2, respectively; P < 0.05). L-arginine, DEA/NO and 8-br-cGMP concentration-dependently inhibited spontaneous contractions in uterine rings both in LPS-treated and -untreated animals. Treatment with LPS significantly attenuated the maximal inhibition induced by l-arginine, DEA/NO and 8-br-cGMP in uterine rings from pregnant mice. Progesterone significantly decreased the levels of IL-6 production (74.9 +/- 12.1, P < 0.05), but not PGE2 and NOx production, and contractile responses by l-arginine, DEA/NO and 8-br-cGMP.

CONCLUSIONS:

The administration of LPS is associated with increases in IL-6, PGE2 and NO, and these increases may or may not have a role to play in LPS-induced preterm labor. Progesterone reduced the LPS-induced increase in IL-6 production and this may be one of the ways that progesterone reduces the risk of preterm labor.

• Authors: Hiroshi Anbe, Toshiaki Okawa, Noboru Sugawara, Hidenori Takahashi, Akira Sato, Yuri P Vedernikov, George R Saade, Robert E Garfield
• Journal: The journal of obstetrics and gynaecology research (J Obstet Gynaecol Res) Vol. 33 Issue 6 Pg. 765-71 (Dec 2007) ISSN: 1341-8076 [Print] Australia
• PMID: 18001439 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Gonadal Hormones
• Interleukin-6
• Lipopolysaccharides
• Nitric Oxide
• Progesterone
• Dinoprostone

Topics

• Animals
• Dinoprostone (biosynthesis)
• Female
• Gonadal Hormones (pharmacology)
• Interleukin-6 (biosynthesis)
• Lipopolysaccharides (pharmacology)
• Mice
• Mice, Inbred C57BL
• Myometrium (drug effects, metabolism)
• Nitric Oxide (biosynthesis)
• Pregnancy
• Progesterone (pharmacology)
• Uterine Contraction (drug effects)