β-Arrestin-dependent signaling in GnRH control of hormone secretion from goldfish gonadotrophs and somatotrophs

Copyright © 2019 Elsevier Inc. All rights reserved..

In goldfish, two native isoforms of gonadotropin-releasing hormone (GnRH2 and GnRH3) stimulate luteinizing hormone (LH) and growth hormone (GH) release from pituitary cells through activation of cell-surface GnRH-receptors (GnRHRs) on gonadotrophs and somatotrophs. Interestingly, GnRH2 and GnRH3 induce LH and GH release via non-identical post-receptor signal transduction pathways in a ligand- and cell-type-selective manner. In this study, we examined the involvement of β-arrestins in the control of GnRH-induced LH and GH secretion from dispersed goldfish pituitary cells. Treatment with Barbadin, which interferes with β-arrestin and β2-adaptin subunit interaction, reduced LH responses to GnRH2 and GnRH3, as well as GH responses to GnRH2; but enhanced GnRH3-induced GH secretion. Barbadin also had positive influences on basal hormone release, and basal GH release in particular, as well as basal activity of extracellular signal-regulated kinase (ERK) and GnRH-induced ERK activation. These findings indicate that β-arrestins play permissive roles in the control of GnRH-stimulated LH release. However, in somatotrophs, β-arrestins, perhaps by mediating agonist-selective endosomal trafficking of engaged GnRHRs, participate in GnRH-isoform-specific GH release responses (stimulatory and inhibitory for GnRH2-GnRHR and GnRH3-GnRHR activation, respectively). The correlative stimulatory influences of Barbadin on basal hormone release and ERK activation suggest that β-arrestins may negatively regulate basal secretion through modulation of basal ERK activity. These results provide the first direct evidence of a role for β-arrestins in hormone secretion from an untransformed primary pituitary cell model, and establish these proteins as important receptor-proximal players in mediating functional selectivity downstream of goldfish GnRHRs.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:287

Enthalten in:

General and comparative endocrinology - 287(2020) vom: 01. Feb., Seite 113340

Sprache:

Englisch

Beteiligte Personen:

Khalid, Enezi [VerfasserIn]
Chang, John P [VerfasserIn]

Links:

Volltext

Themen:

33515-09-2
9002-67-9
9002-72-6
Arrestin-AP2 interaction inhibition
Arrestin-mediated endosomal trafficking
Barbadin
Beta-Arrestins
EC 2.7.11.24
ERK activity
Extracellular Signal-Regulated MAP Kinases
GnRH differential signaling
Gonadotropin-Releasing Hormone
Growth Hormone
Journal Article
LH and GH release
Luteinizing Hormone
Pyrimidines
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 01.06.2020

Date Revised 26.08.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ygcen.2019.113340

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM303808977