title: Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist.
abstract: BACKGROUND
  Long-term treatment with gonadoliberin analogs is used to block the hypothalamic-pituitary-gonadal axis. The use of these agents is generally considered to be safe; however, some observations suggest the possibility of adverse effects.
  
  
  METHODS
  We investigated whether a 3-months administration of a low dose (6 µg/kg b.w.) of dalarelin - a new agonist, and cetrorelix - a known antagonist of GnRH to female rats causes morphological changes in pituitary gland, ovaries, uterus and liver (HE and VG staining); effects on pituitary, hepatic and blood enzyme activities (histochemical and kinetic methods, respectively), and on the blood lipid profile (colorimetric methods); and to what extent these changes are reversible.
  
  
  RESULTS
  Applying analogs effectively inhibited ovulation, affected the uterine endometrium and changed histological appearance of the liver (e.g., steatosis). They altered activities of marker enzymes of cellular respiration, gluconeogenesis and intracellular digestion in the liver and, partially in the pituitary gland, caused undesirable changes in the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase, and a concentration of cholesterol HDL fraction and triglycerides in the blood. Both morphological and enzymatic effects were more evident after antagonist administration; changes in the blood lipid profile were more evident after agonist administration. In both analogs histological and enzymatic changes persisted a relatively long time after the discontinuation of the treatment.
  
  
  CONCLUSIONS
  The low dose of dalarelin and cetrorelix is sufficient to cause limited damage of hepatic cells and may modify the function of pituitary, ovaries, uterus and liver as well as other organs, even after discontinuation of the treatment.
authors: Department of Histology and Embryology, Medical University of Silesia, Katowice, Poland.
authors: Aleksandra
authors: A
authors: Suszka-Świtek
authors: Piotr
authors: P
authors: Czekaj
authors: Jacek
authors: J
authors: Pająk
authors: Rafał
authors: R
authors: Skowronek
authors: Katarzyna
authors: K
authors: Wrona-Bogus
authors: Danuta
authors: D
authors: Plewka
authors: Danuta
authors: D
authors: Kozłowska-Rup
authors: Ryszard
authors: R
authors: Wiaderkiewicz
authors: Andrzej
authors: A
authors: Jankowski
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000097:blood / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000819:agonists* / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects*; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010902:Pituitary Gland / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014599:Uterus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
chemical_list: D004798:Enzymes; C404725:dalarelin; D007987:Gonadotropin-Releasing Hormone; C062876:cetrorelix