Strontium fructose 1,6-diphosphate rescues adenine-induced male hypogonadism and upregulates the testicular endothelin-1 system.
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), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), prepro-endothelin (ET)-1, endothelin-converting enzyme (ECE) and endothelin receptor A (ET(A)) 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 3beta-HSD. In parallel, adenine also targeted the ET-1 system, significantly downregulating mRNA levels of prepro-ET-1, ECE and ET(A). 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.
Feng
Yu
Y
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.
Zhang
Qi
Q
Dai
De-Zai
DZ
Ying
Han-Jie
HJ
Dai
Yin
Y
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000225:Adenine; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D005635:Fructosediphosphates / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D007006:Hypogonadism / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013324:Strontium; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood; D000098682:Steroidogenic Acute Regulatory Protein
D019332:Endothelin-1; D005635:Fructosediphosphates; D010750:Phosphoproteins; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D000225:Adenine; C029063:fructose-1,6-diphosphate; D013324:Strontium