Effects of S-Petasin on Corticosterone Release in Rats

Ling-Ling Chang；Yi-Ching Tseng；Yun-Lian Lin；Wan-Song Alfred Wun；Paulus S. Wang

corticosterone ； S-petasin ； rat ； zona fasciculata-reticularis cells

The Chinese Journal of Physiology

45卷4期（2002 / 12 / 31）

137 - 142

英文

Petasites hybridus is used in Chinese herbal medicine. S-petasin is a bioactive compound isolated from leaves or roots of Petasites hybridus. S-petasin has been used to relieve gastrointestinal pain, lung disease, and spasms of the urogenital tract. However, the side effect of S-petasin on endocrine systems are still not clear. This study explored the effects of S-petasin on the release of corticosterone in vivo and in vitro. An intravenous injection of S-petasin (10μg/kg) decreased both basal and adrenocorticotropin (ACTH)-induced plasma corticosterone concentration in male rats. In vitro, S-petasin (3×10^(-6)-10^(-4) M) caused a significant reduction of basal and ACTH-stimulated release of corticosterone from the enzymatically dispersed rat zona fasciculata-reticularis (ZFR) cells in a dose-dependent manner. In order to study possible mechanisms, ZFR cells were incubated with S-petasin (10^(-5) M) in the presence or absence of forskolin (adenylate cyclase activator, 10^(-6)-10^(-4)M), 8-Br-cAMP (a cAMP analogue, 10^(-6) 10^(-4) M), 25-OH-cholesterol (pregnenolone biosynthesis precursor, 10^(-5) M) combined with trilostane (a blocker of 3β-hydroxysteriod dehydrogenase, 3β-HSD, 10^(-6) M) and deoxycorticosterone (corticosterone biosynthesis precursor, 10^(-9)-10^(-6) M) at 37℃ for lh. The concentration of pregnenolone and corticosterone in media were measured by radioimmunoassay. The stimulatory effects of corticosterone secretion induced by forskolin (10^(-5)-10^(-4) M), 8-Br-cAMP (10^(-5)-10^(-4) M) and deoxycorticosterone (10^(-7)-10^(-6) M) were reduced by S-petasin at 10^(-5) M. The stimulatory effects of pregnenolone secretion induced by 25-OH-cholesterol combined with or without trilostane was reduced by S-petasin at 10^(-5) M. These results suggest that S-petasin inhibits the production of corticosterone from rat ZFR cells in part through decreasing the activities of adenylyl cyclase, P45Oscc and 11β-hydroxylase.

1. Chen, Y.H.,Lo, M.J.,Kau, M.M.,Tsai, S.C.,Chiao, Y.C.,Chen, J.J.,Liaw, C.,Lu, C.C.,Lee, B.P.,Chen, S.C.,Fang, V.S.,Ho, L.T.,Wang, P.S.(1997).Inhibition of corticosterone secretion by thyroxin in male rats.Chinese. J. Physiol.,40,25-30.
2. Clegg, C.H.,Abrahamsen, M.S.,Degen, J.L.,Morris, D.R.,Mcknight, G.S.(1992).Cyclic AMP-dependent protein kinase controls base gene activity and steroidogenesis in Y1 adrenal tumor cells.Biochernistry,31,3720-3726.
3. Debrunner, B.,Neuenschwander, M.(1995).Sesquiterpenes of Petasites hybridus (L.) G. M. et Sch.: Influence of locations and seasons on sesquiterpene distribution.Pharmaceutica Acta Helvetiae,70,315-323.
4. Kau, M.M.,Lo, M.J.,Wang, S.W.,Tsai, S.C.,Chen, J.J.,Chiao, Y.C.,Yeh, J.Y.,Lin, H.,Shum, A.Y.C.,Fang, V.S.,Ho, L.T.,Wang, P.S.(1999).Inhibition of aldosterone production by testosterone in male rats.Metabolism,49,1108-1114.
5. Lin, H.,Chien, C.H.,Lin, Y.C.,Chen, C.F.,Wang, P.S.(2000).Inhibition of testosterone secretion by S-petasin in rat testicular interstitial cells.Chinese. J. Physiol.,43,99-103.
6. Lo, M.J.,Kau, M.M.,Chen, Y.H.,Tsai, S.C.,Chiao, Y.C.,Chen, J.J.,Liaw, C.,Lu, C.C.,Lee, B.P.,Chen, S.C.,Fang, V.S.,Ho, L.T.,Wang, P.S.(1998).Acute effects of thyroid hormones on the production of adrenal cAMP and corticosterone in male rats.Am. J. Physiol.,274,238-245.
7. Mountjoy, K.G.,Bird, I.A.,Rainey, W.E.,Cone, R.D.(1994).ACTN induces up-regulation of ACTH receptor mRNA in mouse and human adrenocortical cell lines.Mol. Cell. Endocrinol.,99,17-20.
8. Penhoat, A.,Jaillard, C.,Saez, J.M.(1994).Regulation of bovine adrenal cell corticotropin receptor mRNA levels by corticotrophin (ACTH) and angiotensin-II (A-II).Mol. Cell. Endocrinol.,103,7-10.
9. Purdy, S.J.,Whitehouse, B.J.,Abayasekara, D.R.E.(1991).Stimulation of steroidogenesis by forskolin in rat adrenal zona glomerulosa preparations.J. Endocrinol,129,391-397.
10. Scheterson, L.C.,McKnight, G.S.(1991).Role of cyclic adenosine 3`, 5`-monophosphate-dependent protein kinase in hormone-stimulated beta-endorphin secretion in AtT20 cells.Mol. Endocrinol.,5,170-178.
11. Schimmer, B.P.(1980).Cyclic nucleotides in hormonal regulation of adrenocortical function.Adv. Cyclic. Neucl. Res.,13,181-214.
12. Simpson, E.R.,McCarthy, J.L.,Peterson, J.A.(1979).Evidence that the cyclohexmide-sensitive site of ACTH action in the mitochondrion.J. Biol. Chem.,253,3135-3139.
13. Simpson, E.R.,Waterman, M.R.(1988).Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH.Annu. Rev. Physiol.,50,427-440.
14. Steel, R.G.D.,Torrie, J.H.(1960).Principles and Procedures of Statistics.New York:McGraw Hill.
15. Tsai, S.C.,Chiao, Y.C.,Lu, C.C.,Doong, M.L.,Chen, Y.H.,Shih, M.C.,Liaw, C.,Wang, S.W.,Wang, P.S.(1996).Inhibition by amphetamine of testosterone secretion through a mechanism involving an increase of cyclic AMP production in rat testes.Br. J. Phormacol,118,984-988.
16. Uneyama, H.,Uneyama, C.,Asaike, N.(1993).Intracellular mechanisms of cytoplasmic Ca(superscript 2+) oscillations in rat megakaryocyte.J. Biol. Chem.,268,167-174.
17. Wang, P.S.,Tsai, S.C.,Hwang, G.S.,Wang, S.W.,Lu, C.C.,Chen, J.J.,Liu, S.R.,Lee, K.Y.,Chien, E.J.,Chien, C.H.,Lee, H.Y.,Lau, C.P.,Tsai, C.L.(1994).Calcitonin inhibits testosterone and luteinizing hormone secretion through a mechanism involving an increase in cAMP production in rats.J Bone Miner. Res.,9,1583-1590.
18. Wong, M.,Krolczyk, A.J.,Schimmer, B.P.(1992).The causal relation ship between mutations in cAMP-dependent protein kinase and the loss of adrenocorticotropin-regulated adrenocortical functions.Mol. Endocrinol,6,1614-1624.
19. Yanagibashi, K.,Papadopoulos, V.,Masaki, E.,Twaki, T.,Kawamura, M.,Hall, P.F.(1989).Forskolin activates voltage-depen dent Ca(superscript 2+) channels in bovine but not in rat fasciculata cells.Endocrinology,124,2383-2391.

1. Wang, Paulus S.,Lo, Ming-Jae(2003).Relative and Combined Effects of Estradiol and Prolactin on Corticosterone Secretion in Ovariectomized Rats.Chinese Journal of Physiology,46(3),103-109.