Leptin Stimulates Prolactin mRNA Expression in the Goldfish Pituitary through a Combination of the PI3K/Akt/mTOR, MKK 3/6/p 38 MAPK and MEK 1/2/ERK 1/2 Signalling Pathways

Int J Mol Sci. 2017 Dec 20;18(12):2781. doi: 10.3390/ijms18122781.


Leptin actions at the pituitary level have been extensively investigated in mammalian species, but remain insufficiently characterized in lower vertebrates, especially in teleost fish. Prolactin (PRL) is a pituitary hormone of central importance to osmoregulation in fish. Using goldfish as a model, we examined the global and brain-pituitary distribution of a leptin receptor (lepR) and examined the relationship between expression of lepR and major pituitary hormones in different pituitary regions. The effects of recombinant goldfish leptin-AI and leptin-AII on PRL mRNA expression in the pituitary were further analysed, and the mechanisms underlying signal transduction for leptin-induced PRL expression were determined by pharmacological approaches. Our results showed that goldfish lepR is abundantly expressed in the brain-pituitary regions, with highly overlapping PRL transcripts within the pituitary. Recombinant goldfish leptin-AI and leptin-AII proteins could stimulate PRL mRNA expression in dose- and time-dependent manners in the goldfish pituitary, by both intraperitoneal injection and primary cell incubation approaches. Moreover, the PI3K/Akt/mTOR, MKK3/6/p38MAPK, and MEK1/2/ERK1/2-but not JAK2/STAT 1, 3 and 5 cascades-were involved in leptin-induced PRL mRNA expression in the goldfish pituitary.

Keywords: expression regulation; goldfish; leptin; pituitary; prolactin; signal pathway.

MeSH terms

  • Animals
  • Cells, Cultured
  • Fish Proteins / genetics
  • Fish Proteins / metabolism*
  • Goldfish
  • Leptin / pharmacology*
  • MAP Kinase Signaling System*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pituitary Gland / drug effects
  • Pituitary Gland / metabolism*
  • Prolactin / genetics
  • Prolactin / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism
  • TOR Serine-Threonine Kinases / metabolism


  • Fish Proteins
  • Leptin
  • RNA, Messenger
  • Receptors, Leptin
  • Prolactin
  • Phosphatidylinositol 3-Kinases
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt