Effects of methanol extract of Chansu on hypothalamic-pituitary-testis function in rats.
Chansu, a galenical preparation of the dried white venom of Chinese Bufo bufo gargarizans, is one of the major components of Kyushin, a traditional Chinese medicine. Kyushin is reported to have a cardiotonic effect that has been suggested to be due to the action of bufadienolides such as bufalin and cinobufagin. Recently, we found that administration of bufalin in male rats diminished the luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) and the secretion of testosterone both in vivo and in vitro. These observations suggest that Chansu may possess hypogonadal effects in male rats. In the present study, the effects of the methanol extract of Chansu on hypothalamic-pituitary-testicular function in male rats were examined. Crude Chansu was extracted by methanol and purified by a Sep-Pak C18 column. No activity of bufalin, cinobufagin, estradiol, or digoxin in purified methanol extract was detected; all Chansu used in this study was the purified methanol extract. A single intravenous injection of Chansu resulted in a decrease of the basal (20% to 55%) and human chorionic gonadotropin (hCG)-induced (35% to 40%) levels of plasma testosterone and the GnRH-induced level of plasma LH (25% to 30%). Administration of Chansu in vitro decreased basal and hCG-stimulated testosterone production by 60% to 70% and 40% to 60%, respectively, as well as spontaneous and forskolin- or 3-isobutyl-1-methylxanthine (IBMX)-induced accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) by 30% to 45% in rat testicular interstitial cells. Although LH release by rat anterior pituitary glands was diminished, GnRH release by the rat mediobasal hypothalamus was enhanced by administration of Chansu in vitro. These results suggest that the bufalin-free extracts of Chansu inhibit testosterone secretion in rats, in part, due to (1) a decreased production of testicular cAMP, (2) a decreased response of testosterone to gonadotropin, and (3) a reduction of the LH response to GnRH.
Wang
S W
SW
Department of Physiology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Lin
H
H
Tsai
S C
SC
Hwu
C M
CM
Chiao
Y C
YC
Lu
C C
CC
Chen
J J
JJ
Wang
G J
GJ
Chou
C J
CJ
Lin
L C
LC
Chen
C F
CF
Wang
P S
PS
D000818:Animals; D002023:Bufo bufo; D000242:Cyclic AMP / Q000096:biosynthesis; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008516:Medicine, Chinese Traditional; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000378:metabolism*
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D000242:Cyclic AMP