PLD.12 Sex hormone cocktail drug - a possible therapeutic target for inhibition of preterm contractions?

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Abstract

Maintenance of uterine quiescence is critical for maintenance of pregnancy and prevention of preterm birth. Progesterone and other sex steroids appear to relax the myometrium but the mechanism of action is unknown. We sought to a) quantify stretch-induced contractions of human and mouse myometrium in vitro following exposure to a variety of sex steroids including Dihydrotestosterone (DHT), Testosterone (T), Estradiol (E2) and Progesterone (P4) and b) examine whether the effect is hormone specific or a generic steroid effect. Myometrial biopsies were obtained from non-labouring women at term and from non-pregnant C57BL/6 mice. Contraction parameters of myometrium under tension were quantified prior to and post-treatment with either each hormone separately (10 μΜ–100 μM) or a “cocktail”, consisting of 10 μM of each.

In human, 100 μΜ of steroid decreased amplitude of contractions to 3.7 ± 2.4% of baseline for DHT, 9.7 ± 2.7% of baseline for T, 1.7 ± 1.7% of baseline for E2 and 21 ± 13.1% of baseline for P4 (n = 7, p < 0.001). In mice, the relevant values were 10.6 ± 5.4% for DHT, 4.9 ± 3% for T, 2.5 ± 3% for E2 and 25 ± 7.4% for P4 (n = 5, p < 0.001). The “cocktail” of 40 uM (10 μM) of each drug decreased amplitude to 58.8% ± 5.4 and 53% ± 3.9 of baseline for human and mouse respectively, which was similar to the decrease induced by individual hormone in equivalent dose (40 μM) (n = 5). These findings suggest that the relaxing action of sex hormones may be generic to, and therefore possibly attributable to their steroid nature. These data may form the basis for development of novel therapeutic approaches for the treatment of preterm contractions.

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