ZFIN ID: ZDB-PUB-170422-5
The GNIH (Lpxrfa) system's regulation of reproduction in the brain-pituitary axis of the zebrafish (Danio rerio)
Spicer, O.S., Zmora, N., Wong, T.T., Golan, M., Levavi-Sivan, B., Gothilf, Y., Zohar, Y.
Date: 2017
Source: Biology of reproduction   96(5): 1031-1042 (Journal)
Registered Authors: Golan, Matan, Gothilf, Yoav, Levavi-Sivan, Berta, Zohar, Yonathan
Keywords: GNIH, Gnrh3, Lpxrfa, reproduction, zebrafish
MeSH Terms:
  • Animals
  • Brain/physiology*
  • Gonadotropin-Releasing Hormone/genetics
  • Gonadotropin-Releasing Hormone/physiology
  • Gonadotropins/genetics
  • Gonadotropins/physiology*
  • Hypothalamic Hormones/genetics
  • Hypothalamic Hormones/physiology*
  • Pituitary Gland/physiology*
  • Reproduction/genetics
  • Reproduction/physiology*
  • Zebrafish/physiology*
PubMed: 28430864 Full text @ Biol. Reprod.
Gonadotropin-inhibitory hormone (GNIH) was discovered in quail with the ability to reduce gonadotropin expression/secretion in the pituitary. There have been few studies on GNIH orthologs in teleosts (Lpxrfa peptides), which have provided inconsistent results. Therefore, the goal of this study was to determine the roles and modes of action by which Lpxrfa exerts its functions in the brain-pituitary axis of zebrafish (Danio rerio). We localized Lpxrfa soma to the ventral hypothalamus, with fibers extending throughout the brain and to the pituitary. In the pre-optic area, Lpxrfa fibers interact with Gnrh3 soma. In pituitary explants, zebrafish peptide Lpxrfa-3 downregulated lhb and common alpha subunit expression. In addition, Lpxrfa-3 reduced gnrh3 expression in brain slices, offering another pathway for Lpxrfa to exert its effects on reproduction. Receptor activation studies, in a heterologous cell-based system, revealed that all three zebrafish Lpxrfa peptides activate Lpxrf-R2 and Lpxrf-R3 via the PKA/cAMP pathway. Receptor activation studies demonstrated that, in addition to activating Lpxrf receptors, zebrafish Lpxrfa-2 and Lpxrfa-3 antagonize Kiss2 activation of Kiss1ra. The fact that kiss1ra-expressing neurons in the pre-optic area are innervated by Lpxrfa-ir fibers suggests an additional pathway for Lpxrfa action. Therefore, our results suggest that Lpxrfa may act as a reproductive inhibitory neuropeptide in the zebrafish that interacts with Gnrh3 neurons in the brain as well as with gonadotropes in the pituitary, while also potentially utilizing the Kiss2/Kiss1ra pathway.