Effects of arecoline on testosterone release in rats.
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 microg/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 degrees 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 17beta-hydroxysteroid dehydrogenase and enhancing the expression of StAR.
Department of Physiology, School of Medicine, Chang Gung University, Kweisan, Taoyuan, Taiwan, ROC. swwang@mail.cgu.edu.tw
Shyi-Wu
SW
Wang
Guey-Shyang
GS
Hwang
Te-Jung
TJ
Chen
Paulus S
PS
Wang
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001115:Arecoline / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology; D015153:Blotting, Western; D020746:Calcium Channels, L-Type / Q000378:metabolism; D018679:Cholinergic Agonists / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D010750:Phosphoproteins / Q000096:biosynthesis; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood*; D000098682:Steroidogenic Acute Regulatory Protein
D044182:Benzylisoquinolines; D020746:Calcium Channels, L-Type; D018679:Cholinergic Agonists; D006063:Chorionic Gonadotropin; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C009438:tetrandrine; D013739:Testosterone; D001115:Arecoline; D009553:Nimodipine; D007986:Luteinizing Hormone; D009543:Nifedipine