title: Valproate inhibits GnRH-induced gonadotropin release from anterior pituitary cells of male rat in vitro.
abstract: OBJECTIVE
  Valproate (VPA) a potent antiepileptic drug has been claimed to induce reproductive disturbances in men. Long-term VPA treatment can affect sperm morphology and induce testicular atrophy in non-epileptic rats. It has been reported that VPA reduced testosterone secretion stimulated by hCG in isolated rat Leydig cells. These results suggest direct effect of VPA on testes in rats. However centrally mediated effects at hypothalamo-pituitary level can therefore not be excluded. This study focused on the dose and time-dependent effects of VPA on basal and GnRH-induced LH and FSH release from the primary anterior pituitary cells culture of male rats.
  
  
  METHODS
  The dose-dependent effect of 10 nM-100 mM of VPA on basal LH release from anterior pituitary cells after 3h of incubation was examined. To determine the time-dependent effects on LH, FSH, TSH and PRL release short (3 h) and long-term (24 h) incubations in the presence of 10 nM, 100 nM and 1 μM of VPA were maintained.To assess whether VPA can affect GnRH-induced LH and FSH release, cells were incubated for 3 h with 10 nM, 100 nM and 1 μM of VPA in the presence of GnRH. The concentration of rLH, rFSH, rPRL and rTSH in incubation medium was determined by RIA method.
  
  
  RESULTS
  VPA did not affect the basal LH, FSH, PRL and TSH release from the primary anterior pituitary cells culture of male rats. VPA in concentration 1µM significantly suppressed GnRH-induced LH secretion. However VPA at all tested doses diminished GnRH-induced FSH release.
  
  
  CONCLUSIONS
  VPA may diminish gonadotropin release in vitro but this effect can only be achieved after GnRH-dependent specific receptor activation. Both gonadotropins differ in their pattern of response for increasing doses of VPA.
authors.affiliation: Department of Neuroendocrinology, Medical Centre of Postgraduate Education, Warsaw, Poland. zncmkp@op.pl
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Wasilewska-Dziubinska
authors.forename: Alina
authors.initials: A
authors.lastname: Gajewska
authors.forename: Ewa
authors.initials: E
authors.lastname: Wolinska-Witort
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chmielowska
authors.forename: Lidia
authors.initials: L
authors.lastname: Martynska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Elbanowski
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kochman
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D006062:Gonadotropins / Q000378:metabolism*; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000378:metabolism; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D006062:Gonadotropins; D007987:Gonadotropin-Releasing Hormone; D014635:Valproic Acid; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin