Title

Molecular Cloning and Pharmacological Characterization of Two Novel GnRH Receptors in the Lamprey (Petromyzon marinus)

Abstract

This paper reports the identification, expression, binding kinetics, and functional studies of two novel type III lamprey GnRH receptors (IGnRH-R-2 and IGnRH-R-3) in the sea lamprey, a basal vertebrate. These novel GnRH receptors share the structural features and amino acid motifs common to other known gnathostome GnRH receptors. The ligand specificity and activation of intracellular signaling studies showed ligands IGnRH-II and -III induced an inositol phosphate (IP) response at IGnRH-R-2 and IGnRH-R-3, whereas the ligand IGnRH-I did not stimulate an IP response. IGnRH-II was a more potent activator of lGnRH-R-3 than IGnRH-II. Stimulation of IGnRH-IIR-2 and IGnRH-R-3 testing all three IGnRH ligands did not elicit a cAMP response. IGnRH-R-2 has a higher binding affinity in response to IGnRH-R-2 than IGnRH-R-2, whereas IGnRH-R-3 has a higher binding affinity in response to IGnRH-R-2 than IGnRH-III. IGnRH-R-2 precursor transcript was detected in a wide variety of tissues including the pituitary whereas lGnRH-R-3 precursor transcript was not as widely expressed and primarily expressed in the brain and eye of male and female lampreys. From our phylogenetic analysis, we propose that IGnRH-R-1 evolved from a common ancestor of all vertebrate GnRH receptors and IGnRH-R-2 and lGnRH-R-3 likely occurred due to a gene duplication within the lamprey lineage. In summary, we propose from our findings of receptor subtypes in the sea lamprey that the evolutionary recruitment of specific pituitary GnRH receptor subtypes for particular physiological functions seen in later evolved vertebrates was an ancestral character that first arose in a basal vertebrate. (Endocrinology 153: 3345-3356, 2012)

Publication Date

7-1-2012

Journal Title

Endocrinology

Publisher

Endocrine Society

Digital Object Identifier (DOI)

10.1210/en.2012-1217

Scientific Contribution Number

2472

Document Type

Article

Rights

Copyright © 2012 by The Endocrine Society