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Am J Physiol Endocrinol Metab 295: E497-E504, 2008. First published June 17, 2008; doi:10.1152/ajpendo.00045.2008
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Effects of arecoline on testosterone release in rats

Shyi-Wu Wang,1,* Guey-Shyang Hwang,2,3 Te-Jung Chen,2 and Paulus S. Wang2,*

1Department of Physiology and Pharmacology, Chang Gung University, Taoyuan3; 2Department of Physiology, School of Medicine, National Yang-Ming University, Taipei; and 3Department of Nursing, Chang Gung Institute of Technology, Taoyuan, Taiwan, Republic of China

Submitted 23 January 2008 ; accepted in final form 16 June 2008

Arecoline is one of the major components of betel nuts, which have been consumed as chewing gum in Southeast Asia. In this study, the effects of arecoline on testosterone (T) secretion were explored. Male rats were injected with human chorionic gonadotropin (hCG, 5 IU/kg) or arecoline (1 µg/kg) plus hCG via a jugular catheter. Blood samples were collected at several time intervals subsequent to the challenge. Rat anterior pituitary was treated with gonadotropin-releasing hormone in vitro with or without arecoline, and then the concentrations of luteinizing hormone (LH) in the medium were measured. Rat Leydig cells were purified by Percoll density gradient centrifugation and incubated with arecoline, hCG, forskolin, 8-bromo-cAMP (8-Br-cAMP), nifedipine, nimodipine, or tetrandrine at 34°C for 1 h. A single intravenous injection of arecoline resulted in an increase of the hCG-induced level of plasma T. Administration of arecoline (10–8 to 10–6 M) in vitro increased T production in Leydig cells. The stimulatory effect of arecoline on T release in vitro was enhanced by hCG (0.001 IU/ml), forskolin (10–6 M), or 8-Br-cAMP (10–5 M). By contrast, nifedipine, nimodipine, or tetrandrine inhibited the increased T concentrations induced by arecoline. Western blot showed that arecoline increases steroidogenic acute regulatory (StAR) protein expression compared with vehicle. These results suggested that arecoline stimulates testosterone production by acting directly on Leydig cells via mechanisms involving an activation of L-type calcium channels, increasing the activity of 17β-hydroxysteroid dehydrogenase and enhancing the expression of StAR.

arecoline; Leydig cell; L-type calcium channel; testosterone


Address for reprint requests and other correspondence: S.-W. Wang, Dept. of Physiology, School of Medicine, Chang Gung Univ., Kweisan, Taoyuan, 33333, Taiwan, ROC (e-mail: swwang{at}mail.cgu.edu.tw)






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