title: Clomiphene citrate potentiates the adverse effects of estrogen on rat testis and down-regulates the expression of steroidogenic enzyme genes.
abstract: OBJECTIVE
  To investigate the antiestrogenic effect of clomiphene citrate (CC) in male rats estrogenized with estradiol-3-benzoate (EB).
  
  
  METHODS
  Prospective experimental study.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Adult male albino rats (Holtzman strain).
  
  
  METHODS
  CC was given alone or in combination with EB.
  
  
  METHODS
  Testicular function and steroidogenic enzyme gene expression were evaluated in control versus treated groups.
  
  
  RESULTS
  EB after 30 days of treatment induced a rise in TUNEL-positive germ cells adversely affecting spermatogenesis with complete absence of elongated spermatids or sperms. CC alone had only a moderate effect. In contrast, CC+EB synergistically inflicted more adverse effects as apoptotic germ cells per tubule rose further. Significant down-regulation in expression of testicular steroidogenic enzyme genes StAR, p450scc, 3β-HSD, and p450c17 was observed. In the EB-alone group, aromatase gene expression in the testis was up-regulated but reversed in brain and liver tissues. CC alone had little modulatory effect on aromatase expression. On the other hand, CC+EB countered the EB-induced rise of aromatase expression in the testis.
  
  
  CONCLUSIONS
  The above findings indicate that CC in the presence of estrogen synergistically potentiates more adverse effects in testis, inhibiting expression of upstream steroidogenic enzyme genes and leading to disruption of steroidogenesis.
authors.affiliation: Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi, India; Department of Zoology, University of Delhi, New Delhi, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Bharti
authors.affiliation: Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi, India. Electronic address: mm_misro@yahoo.com.
authors.forename: M M
authors.initials: MM
authors.lastname: Misro
authors.affiliation: Department of Zoology, University of Delhi, New Delhi, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Rai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D002996:Clomiphene / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D004357:Drug Synergism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D002996:Clomiphene; C074283:estradiol 3-benzoate; D004958:Estradiol; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme