Brain thromboxane A2 via arachidonic acid cascade induces the hypothalamic-pituitary-gonadal axis activation in rats

Auton Neurosci. 2015 May:189:50-5. doi: 10.1016/j.autneu.2015.02.005. Epub 2015 Mar 6.

Abstract

The current study was designed to determine the effect of centrally administrated arachidonic acid (AA) on plasma gonadotropin hormone-releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone level, and sperm parameters, and to show the mediation of the central cyclooxygenase (COX) to thromboxane A2 (TXA2) signaling pathway in AA-induced hormonal and sperm parameter effects. Studies were performed in male Sprague-Dawley rats. A total of 150 or 300 μl/5 μl doses of AA were injected intracerebroventricularly (icv). AA significantly caused dose- and time-dependent increases in plasma FSH, LH and testosterone levels of animals, but not plasma GnRH level. AA also significantly increased sperm motility of the rats without change sperm number. Pretreated with ibuprofen, a nonselective COX inhibitor (250 μg/5 μl; icv), and furegrelate, a TXA2 synthesis inhibitor (250 μg/5 μl; icv), prevented AA-evoked increase in plasma FSH, LH and testosterone levels, and sperm motility. In conclusion, our findings show that centrally administered AA increases plasma FSH, LH and testosterone levels and sperm motility of conscious male rats. Moreover, according to our findings, central COX-TXA2 signaling pathway mediates these AA-induced effects.

Keywords: Arachidonic acid; Cyclooxygenase; Hypothalamic–pituitary–gonadal axis; Intracerebroventricular; Sperm parameters; Thromboxane A(2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / administration & dosage*
  • Benzofurans / pharmacology
  • Brain / drug effects*
  • Brain / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Follicle Stimulating Hormone / blood
  • Growth Hormone-Releasing Hormone / blood
  • Ibuprofen / pharmacology
  • Infusions, Intraventricular
  • Luteinizing Hormone / blood
  • Male
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Sperm Count
  • Sperm Motility / drug effects
  • Testosterone / blood
  • Thromboxane A2 / metabolism*
  • Time Factors

Substances

  • Benzofurans
  • Enzyme Inhibitors
  • Arachidonic Acid
  • Testosterone
  • Thromboxane A2
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Growth Hormone-Releasing Hormone
  • Prostaglandin-Endoperoxide Synthases
  • furegrelate
  • Ibuprofen