Background: The impact of androgens on myometrial contraction has received less scrutiny, compared to progesterone and estrogens. We sought to i) examine the effect of dihydrotestosterone (DHT; a non-aromatizable androgen) on stretch-induced contraction of human myometrium and ii) gain mechanistic insights by studying changes in intracellular calcium [Ca2+] and phosphorylation of myosin light chain (MLC).
Methods: Myometrial strips were recovered from biopsies obtained from women undergoing elective caesarean delivery at term prior initiation of labour. Strips were placed under tension in a tissue-bath system and allowed to develop spontaneous contractions. Contractions were quantified before and after addition of DHT (10100 μM, 30 min). A myometrial smooth muscle cell line (PHM1-41s) was used to measure [Ca2+] concentrations (Fluo-4 calcium assays) and phosphorylation of MLC (in-cell western); oxytocin (OXT) was used as a positive control.
Results: Addition of DHT relaxed spontaneous myometrial contractions in a dose dependent fashion: amplitude of contractions was 5%±3% of controls following addition of 100 μM (n=7 women, P<0.001). Treatment of PHM1-41s with OXT (10 nM) increased [Ca2+] (P<0.001, n=7) and significantly increased phosphorylation of MLC (OXT 100 nM, P<0.0001, n=6). Pre-treatment with DHT for 15 min blunted the OXT effect on [Ca2+] (DHT: 800 nM; P<0.05, n=6) and phosphorylation of MLC (DHT: 50 μM; P<0.05, n=6).
Conclusions: DHT inhibits myometrial smooth muscle contraction. The mechanism of this effect may involve the blockage of increases in intracellular Ca2+ and phosphorylation of MLC.
02 Sep 2014 - 04 Sep 2014