title: Complete sperm suppression induced by dienogest plus testosterone undecanoate is associated with down-regulation in the expression of upstream steroidogenic enzyme genes in rat testis.
abstract: BACKGROUND
  We had shown that dienogest (DNG) + testosterone undecanoate (TU) induced complete sperm suppression in rats when administered together every 45 days. On the other hand, individual drugs given alone in a similar fashion failed to achieve the same result.
  
  
  METHODS
  The present study was therefore undertaken to determine the reason for such a differential sperm suppression and to correlate it with the expression of steroidogenic enzyme genes in the rat testis.
  
  
  RESULTS
  Administration of DNG (40 mg/kg body weight [bw]) + TU (25 mg/kg bw) every 45 days for a duration of 90 days induced spermatogenic arrest, leading to a significant reduction in testicular weight and number of precursor germ cells. Flow cytometric analysis further confirmed the same result, leading to a significant shift in the distribution of haploid cells. Measurement of testosterone (serum and intratesticular) was significantly low. Complete sperm suppression coincided with significant down-regulation in the expression of upstream steroidogenic enzyme genes represented serially by cytochrome P450 side-chain cleavage, P450 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein (StAR) in the testis. On the other hand, rats administered with either DNG or TU alone demonstrated incomplete sperm suppression in which the expression of all the above genes remained characteristically nonuniform.
  
  
  CONCLUSIONS
  Taken together, the above findings corroborate the fact that regulation of expression of three of the upstream steroidogenic enzymes genes and the StAR protein in rat testis is crucial in leading to complete sperm suppression as observed with DNG+TU treatment.
authors.affiliation: Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Munirka, New Delhi-110067, India.
authors.forename: Rekha
authors.initials: R
authors.lastname: Meena
authors.forename: Man Mohan
authors.initials: MM
authors.lastname: Misro
authors.forename: Debidas
authors.initials: D
authors.lastname: Ghosh
authors.forename: Deoki
authors.initials: D
authors.lastname: Nandan
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003272:Contraceptive Agents, Male / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D004357:Drug Synergism; D007273:Injections, Intramuscular; D008297:Male; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012671:Seminiferous Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000728:Androgens; D003272:Contraceptive Agents, Male; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; C023635:dienogest; D009277:Nandrolone; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; C010792:testosterone undecanoate