Differential effects of dexamethasone and RU 486, an antigestagen and antiglucocorticoid, on progesterone and relaxin secretion in hysterectomized pigs with aging corpora lutea

Pregnancy lasts about 114 days in pigs. Porcine corpora lutea produce not only progesterone but also relaxin (RLX), a peptide hormone that plays a critical role in suppressing uterine motility during pregnancy and in remodelling connective tissues in preparation for imminent parturition. Progesterone concentrations in peripheral blood remain elevated (≈25 ng ml−1) for the major part of pregnancy and decrease just before parturition. The decrease in progesterone coincides with the peak prepartum RLX release. Glucocorticoid or antiglucocorticoid steroid, RU 486, administration during late pregnancy can induce parturition in the pig. Peak release of RLX and a coincident decrease of progesterone in the circulating blood can also occur in the complete absence of fetuses and uterus in the pig. The effects of glucocorticoid or antiglucocorticosteroid administration to such hysterectomized pigs on the secretion of RLX and progesterone were examined in this experiment. Unmated Yorkshire gilts were hysterectomized on days 6–8 (estrus=day 0) and given dexamethasone (total of 30 mg day−1; 2 times i.m. at 0800 and 1600 h) from days 110–118; control animals received vehicle injection during this period. RU 486 (4 mg kg1 body weight) was orally administered once daily (days 111–115) at 0800 h; placebo-treated controls were given the same amount of feed without the drug at this time. RLX concentrations in blood were markedly suppressed (P<0.01) during dexamethasone treatment (3±0.9 ng ml−1; mean±S.E.) whereas a peak release of RLX (17±2.8 ng ml−1) occurred in the control group on day 113. In contrast, progesterone concentrations (14±2.5 ng ml−1) were unaffected by dexamethasone treatment compared with the controls (15±2.0 ng ml−1; P>0.82). Upon withdrawal of dexamethasone on day 118, RLX plasma concentrations began to increase and peaked at 14±2.1 ng ml−1 (P<0.01) on day 120. In contrast, the antiglucocorticosteroid given to hysterectomized pigs bearing aging corpora lutea caused a marked elevation in circulating levels of progesterone and delayed RLX release until after the end of drug treatment on day 115. Average weights of corpora lutea collected at day 125 were similar between treated and control groups (427±7 vs. 433±6 mg; P>0.68). Results indicate that a synthetic glucocorticoid, dexamethasone, suppresses RLX secretion without causing luteolysis and such suppression is reversible; progesterone secretion remained unaffected. In contrast, the antiglucocorticoid, RU 486, raised progesterone plasma concentration and delayed RLX peak release but did not suppress it during treatment. This experiment provides further evidence that relaxin and progesterone secretion from aging corpora lutea of pigs are regulated through separate mechanisms, and adrenal glucocorticoids may be involved in such a regulation process.