Effects of Propylthiouracil on the Production of Aldosterone in Rat Zona Glomerulosa Cells

Hsiao-Fung Pu ； Chia-Wen Lin ； Hsiao-Wei Lee ； Paulus S. Wang

《Adaptive Medicine》 4卷4期 (2012/12) Pp. 245-250

https://doi.org/10.4247/AM.2012.ABC045

並列摘要

Propylthiouracil (PTU), an anti-thyroid drug, is widely used for the treatment in hyperthyroid patients. Previous studies indicate that thyroxine inhibit the spontaneous and adrenocorticotropin (ACTH)-stimulated corticosterone secretion by acting directly at adrenal glands via decrease cAMP production. It has also been shown that PTU suppresses corticosterone release by male rat zona fasciculata-reticularis cells. However, the direct effects and mechanisms of PTU on the aldosterone production in adrenal zona glomerulosa (ZG) cells are still unclear. ZG cells were prepared from adrenocortical tissues of male rats, and then challenged with or without angiotensin II (10^(-7), 10^(-6) M), ACTH (10^(-9) M), A23187 (10^(-5) M), cyclopiazonic acid (CPA, 10^(-5) M), forskolin (10^(-5) M), 8-Br-cAMP (10^(-5) M), trilostane (10^(-6) M, 3β-HSD inhibitor) or steroidogenic precursors (e.g. 10^(-6) M 25-OH-cholesterol and 10^(-7), 10^(-5) M corticosterone) at 37°C for 1 h. Our results showed that PTU (0-3 mM) dose-dependently decreased the aldosterone release in response to the above hormones, drugs and the steroidogenic precursors in vitro. PTU also decreased steroidogenic acute regulatory (StAR) protein expression, but did not alter the protein expression of P450 side chain cleavage enzyme (P450scc) during steroidogenesis of aldosterone. These results suggested that PTU has a direct inhibitory effect on aldosterone production via cAMP, and Ca^2+ down stream pathway and the steroidogenic enzymes activities including P450scc and aldosterone synthase, as well as StAR protein expression.

並列關鍵字

adrenal gland ； aldosterone ； cAMP ； calcium ； P450scc ； PTU ； StAR protein ； ZG cell