Effects of Amphetamine on the Release of Corticosterone and Aldosterone in Rat Adrenocortical Cells

Shiow-Chwen Tsai ； Mei-Mei Kau ； Paulus S. Wang

《Adaptive Medicine》 11卷4期 (2019/12) Pp. 127-132

https://doi.org/10.4247/AM.2019.ABJ239

摘要

Scientists found that amphetamine deregulated the hypothalamus-pituitary-adrenal (HPA) axis function in animals and human. Also, amphetamine attenuated the release of testosterone has been reported by our previous study. However, the effects of amphetamine on the adrenocortical cells in vitro are still unknown. The present investigation is to study the direct effects and the associated mechanisms of amphetamine on the production of aldosterone and corticosterone by rat adrenocortical cells. The rat adrenocortical cells, zona glomerulosa (ZG) cells and zona fasciculata-reticularis (ZFR) cells were isolated and incubated at 37°C for 1 h with or without adrenocorticotropin (ATCH), forskolin (a protein kinase A activator), 8-bromo-cAMP (8-BrcAMP, an analogue of cAMP), cholera toxin (a Gs protein activator), steroidogenic precursors including 25-hydroxycholesterol (25-OHC), pregnenolone (P5), progesterone (P4), deoxycorticosterone (DOC), corticosterone, nicotinic acid-adenine dinucleotide phosphate (NAADP), cyclopiazonic acid (CPA), A23187 and Bay K 8644 in the presence or absence of amphetamine (10^(-10)~10^(-6) M). At the end of incubation, the media were collected and measured for aldosterone and corticosterone by radioimmunoassays (RIA), respectively. The results were expressed by mean ± standard error of the mean (SEM) and analyzed by the analysis of variance (ANOVA) and Duncan's multiple range test. The results indicated that amphetamine inhibited the basal release of corticosterone in a dose dependent manner. Administration of ACTH, forskolin, 8-Br-cAMP, and cholera toxin not only significantly increased the release of corticosterone and also reversed the inhibited corticosterone release in response to amphetamine in ZFR cells. The steroidogenic precursors markedly induced the release of corticosterone. The attenuated release of corticosterone caused by amphetamine could be totally reversed by treatment of 25-OHC, P5, P4 but DOC in rat ZFR cells. Amphetamine exhibited the influence neither on basal-nor the stimulant-induced aldosterone release in rat ZG cells. These data indicated that amphetamine exhibited a rapid and direct inhibitory effect on release of corticosterone but aldosterone through inhibition of Gs-adenylyl cyclase-cAMP pathway and steroidogenic enzymes activities including P450scc, and 3β-hydroxysteroid dehydrogenase (3β- HSD) in rat adrenocortical cells.

關鍵字

25-hydroxycholesterol ； 3β-HSD ； adenylyl cyclase ； P450scc