Cimetidine disrupts the renewal of testicular cells and the steroidogenesis in a hermaphrodite fish

Comp Biochem Physiol C Toxicol Pharmacol. 2016 Nov:189:44-53. doi: 10.1016/j.cbpc.2016.07.004. Epub 2016 Jul 27.

Abstract

The importance of histamine in the physiology of the testis in mammals and reptiles has been recently shown. Histamine receptors (Hrs) are well conserved in fish and are functional in several fish species. We report here for the first time that histamine and the mRNA of Hrh1, Hrh2 and Hrh3 are all present in the gonad of the hermaphrodite teleost fish gilthead seabream. Moreover, cimetidine, which acts in vitro as an agonist of Hrh1 and Hrh2 on this species, was intraperitoneally injected in one and two years old gilthead seabream males. After three and five days of cimetidine injection, we found that this compound differently modified the gonadal hrs transcript levels and affects the testicular cell renewal and the gene expression of steroidogenesis-related molecules as well as the serum steroid levels. Our data point to cimetidine as a reproductive disruptor and elucidate a role for histamine in the gonad of this hermaphrodite fish species through Hr signalling.

Keywords: Cimetidine; Hermaphrodite fish; Histamine receptors; Testis.

MeSH terms

  • Animals
  • Cimetidine / toxicity*
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Fish Proteins / drug effects
  • Fish Proteins / genetics
  • Fish Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Gonadal Steroid Hormones / biosynthesis*
  • Hermaphroditic Organisms*
  • Histamine H2 Antagonists / toxicity*
  • Male
  • Receptors, Histamine H1 / drug effects
  • Receptors, Histamine H1 / genetics
  • Receptors, Histamine H1 / metabolism
  • Receptors, Histamine H2 / drug effects
  • Receptors, Histamine H2 / genetics
  • Receptors, Histamine H2 / metabolism
  • Receptors, Histamine H3 / drug effects
  • Receptors, Histamine H3 / genetics
  • Receptors, Histamine H3 / metabolism
  • Regeneration / drug effects*
  • Sea Bream / genetics
  • Sea Bream / growth & development
  • Sea Bream / metabolism*
  • Signal Transduction / drug effects
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / physiopathology
  • Time Factors

Substances

  • Endocrine Disruptors
  • Fish Proteins
  • Gonadal Steroid Hormones
  • Histamine H2 Antagonists
  • Receptors, Histamine H1
  • Receptors, Histamine H2
  • Receptors, Histamine H3
  • Cimetidine