This investigation aimed to see whether a change in the oestrogen to androgen ratio alters prostate contractility. Isolated organ bath studies using prostates from aromatase knockout (ArKO) mice which were homozygous (ArKO−/−) and heterozygous (ArKO+/−) for the disrupted aromatase cyp19 gene and wild-type littermates (ArKO+/+) were conducted. The distribution of noradrenergic nerves was visualized using the sucrose–potassium phosphate–glyoxylic acid method. ArKO−/− mice had increased prostate weights compared with ArKO+/+ mice. Frequency–response curves to electrical field stimulation (EFS; 0.5 ms pulse duration, 60 V, 0.1–20 Hz) yielded frequency-dependent contractions, while noradrenaline (10 nM–1 mM) and tyramine (1 μM–1 mM) produced concentration-dependent contractions. Prazosin (0.3 μM) attenuated the responses induced by noradrenaline and EFS in all mice (P≤0.019, n=5–7), while cocaine (10 μM) attenuated the responses evoked by tyramine (P<0.001, n=6). There were no genotype differences in EFS- and noradrenaline-induced responses (P≥0.506, n=10–13). Prostates from ArKO−/− and ArKO+/− mice were more sensitive to tyramine than prostates from ArKO+/+ mice (P<0.001, n=11–13). Dense adrenergic innervation of the prostate was similar in all mice. These results suggest that although the absence of aromatase increases prostatic growth, this translates only to a subtle and selective increase in contractility in mature mice.
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Katherine T Gray, Jennifer L Short, Evan R Simpson, and Sabatino Ventura
L Sabatino, AG Cerillo, A Ripoli, A Pilo, M Glauber, and G Iervasi
The cardiovascular system is an important target for thyroid hormones. The present study evaluates the changes affecting thyroid hormone metabolism during and 6 days after coronary artery bypass and their relationship with the post-operative outcome of the patients. Thirty-three patients were enrolled in the study; their thyroid hormone profiles were determined at 13 sampling points during surgery and for 6 days afterwards. Serum total tri-iodothyronine (T3) and free T3 (FT3) concentrations decreased significantly after surgery (P<0.001) and they remained significantly low until the end of the study. Free thyroxine (FT4) and T4 declined significantly immediately after surgery (P<0.05 for FT4, P<0.001 for T4) but they returned to baseline values (24 h and 96 h post-surgery respectively). Serum reverse T3 increased remarkably 36 h after surgery (P<0.001) and remained significantly higher than the baseline value throughout the study. A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period. Our data suggest a prolonged reduction of T4 to T3 conversion in patients undergoing cardiac surgery and indicate that the recovery period is the most critical in the evaluation of a possibly successful approach for T3 substitutive therapy.