Effects of evodiamine and rutaecarpine on the secretion of corticosterone by zona fasciculata-reticularis cells in male rats.
Evodiamine (EVO) and rutaecarpine (RUT) are two bioactive alkaloid isolated from Chinese herb named Wu-Chu-Yu. Previous studies have shown that EVO and RUT possess thermoregulation, vascular regulation, anti-allergic, anti-nociceptive and anti-inflammatory activities. The mechanisms of EVO and RUT effect on steroidogenesis are not clear. The goal of this study was to characterize the mechanism by which EVO and RUT affect corticosterone production in rat zona fasciculata-reticularis (ZFR) cells. ZFR cells were isolated from adrenal glands of male rats and incubated with adrenalcorticotropin (ACTH, 10(-9) M), forskolin (an adenylyl cyclase activator, 10(-5) M), 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP, a permeable cAMP analog, 10(-4) M), or steroidogenic precursors including 25-hydroxycholesterol, pregnenolone, progesterone, and deoxycorticosterone, 10(-5) M each, in the presence or absence of EVO and RUT respectively (0-10(-3) M) at 37 degrees C for 1 h. The concentrations of corticosterone, pregnenolone and progesterone in the media were measured by radioimmunoassay. After administration of ZFR cells with EVO or RUT (10(-4) M) for 60 and 120 min, Western blot analysis was employed to explore the influence of EVO and RUT on the expression of cytochrome P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory protein (StAR). EVO and RUT reduced both basal and ACTH-, forskolin-, as well as 8-Br-cAMP-stimulated corticosterone production in rat ZFR cells. The enhanced corticosterone production caused by the administration of four steroidogenic precursors was decreased following EVO or RUT challenge. These results suggest that EVO and RUT inhibit corticosterone production in rat ZFR cells via a mechanism involving: (1) a decreased activity of cAMP-related pathways; (2) a decreased activity of the steroidogenic enzymes, that is, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 11beta-hydroxylase (P450c11), during steroidogenesis; and (3) an inhibition of StAR protein expression.
Yu
Po-Ling
PL
Department of Surgery, Taipei City Hospital, Taipei 10431, Taiwan, Republic of China.
Chao
Hsu-Li
HL
Wang
Shyi-Wu
SW
Wang
Paulus S
PS
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism; D003345:Corticosterone / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives; D003900:Desoxycorticosterone / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D032086:Evodia / Q000737:chemistry; D006888:Hydroxycholesterols / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology*; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011284:Pregnenolone / Q000032:analysis / Q000378:metabolism; D011374:Progesterone / Q000032:analysis / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014665:Vasodilator Agents / Q000494:pharmacology*; D015383:Zona Fasciculata / Q000166:cytology* / Q000378:metabolism; D015385:Zona Reticularis / Q000166:cytology* / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein; D052999:Quinazolinones
D015096:3-Hydroxysteroid Dehydrogenases; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000324:Adrenocorticotropic Hormone; D002786:Cholesterol Side-Chain Cleavage Enzyme; D005576:Colforsin; D003345:Corticosterone; D000242:Cyclic AMP; D003900:Desoxycorticosterone; D004365:Drugs, Chinese Herbal; D006888:Hydroxycholesterols; D026121:Indole Alkaloids; D010750:Phosphoproteins; D010936:Plant Extracts; D011284:Pregnenolone; D011374:Progesterone; D011799:Quinazolines; D014665:Vasodilator Agents; D000098682:Steroidogenic Acute Regulatory Protein; C007997:25-hydroxycholesterol; C028632:rutecarpine; D052999:Quinazolinones; C049639:evodiamine