TY - JOUR
T1 - Strontium fructose 1,6-diphosphate rescues adenine-induced male hypogonadism and upregulates the testicular endothelin-1 system
AU - Feng, Yu
AU - Zhang, Qi
AU - Dai, De Zai
AU - Ying, Han Jie
AU - Dai, Yin
PY - 2007/11
Y1 - 2007/11
N2 - 1. Male hypogonadism is a major problem that starts to affect middle-aged men and has adversely effects on human sexual life. The aim of the present study was to investigate the effect of strontium fructose 1,6-diphosphate (FDP-Sr) on male hypogonadism in rats. 2. The pharmacological model of testis dysfunction was created by administration of adenine (200 mg/kg per day, i.g.) for 30 days. Three doses of FDP-Srs (200, 100 and 50 mg/kg per day, i.g.) were administered in parallel with adenine. Finally, mating behaviour index (the mounting latency and the number of mounting events), the total number of spermatozoa and sperm motility, related enzyme function and gene regulation and the mRNA levels of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), prepro-endothelin (ET)-1, endothelin-converting enzyme (ECE) and endothelin receptor A (ETA) were analysed. 3. The results showed that adenine significantly prolonged the mounting latency and decreased the number of mounting events, markedly reduced the total number of spermatozoa, slowed sperm motility and decreased testicular enzyme activity in the testes. At the mRNA level, adenine significantly downregulated serum testosterone, StAR, P450sc and 3β-HSD. In parallel, adenine also targeted the ET-1 system, significantly downregulating mRNA levels of prepro-ET-1, ECE and ETA. Administration of FDP-Sr dose-dependently reversed these effects. 4. In conclusion, adenine-induced testis dysfunction appears to be manifested as loss of sexual function in association with decreased spermatogenesis and reduced mRNA levels of steroidogenesis and the testicular ET-1 system. These abnormalities were significantly restored by FDP-Sr in a dose-dependent manner. These data indicate the possibility of using FDP-Sr to treat male hypogonadism.
AB - 1. Male hypogonadism is a major problem that starts to affect middle-aged men and has adversely effects on human sexual life. The aim of the present study was to investigate the effect of strontium fructose 1,6-diphosphate (FDP-Sr) on male hypogonadism in rats. 2. The pharmacological model of testis dysfunction was created by administration of adenine (200 mg/kg per day, i.g.) for 30 days. Three doses of FDP-Srs (200, 100 and 50 mg/kg per day, i.g.) were administered in parallel with adenine. Finally, mating behaviour index (the mounting latency and the number of mounting events), the total number of spermatozoa and sperm motility, related enzyme function and gene regulation and the mRNA levels of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), prepro-endothelin (ET)-1, endothelin-converting enzyme (ECE) and endothelin receptor A (ETA) were analysed. 3. The results showed that adenine significantly prolonged the mounting latency and decreased the number of mounting events, markedly reduced the total number of spermatozoa, slowed sperm motility and decreased testicular enzyme activity in the testes. At the mRNA level, adenine significantly downregulated serum testosterone, StAR, P450sc and 3β-HSD. In parallel, adenine also targeted the ET-1 system, significantly downregulating mRNA levels of prepro-ET-1, ECE and ETA. Administration of FDP-Sr dose-dependently reversed these effects. 4. In conclusion, adenine-induced testis dysfunction appears to be manifested as loss of sexual function in association with decreased spermatogenesis and reduced mRNA levels of steroidogenesis and the testicular ET-1 system. These abnormalities were significantly restored by FDP-Sr in a dose-dependent manner. These data indicate the possibility of using FDP-Sr to treat male hypogonadism.
KW - Adenine
KW - Endothelin
KW - Hypogonadism
KW - Steroidogenic acute regulatory protein
KW - Strontium fructose 1,6-diphosphate
KW - Testosterone
UR - http://www.scopus.com/inward/record.url?scp=34548675166&partnerID=8YFLogxK
U2 - 10.1111/j.1440-1681.2007.04693.x
DO - 10.1111/j.1440-1681.2007.04693.x
M3 - 文章
C2 - 17880366
AN - SCOPUS:34548675166
SN - 0305-1870
VL - 34
SP - 1131
EP - 1137
JO - Clinical and Experimental Pharmacology and Physiology
JF - Clinical and Experimental Pharmacology and Physiology
IS - 11
ER -