AUTHOR=Fleming Mitchell Stewart , Maugars Gersende , Martin Patrick , Dufour Sylvie , Rousseau Karine 

TITLE=Differential Regulation of the Expression of the Two Thyrotropin Beta Subunit Paralogs by Salmon Pituitary Cells In Vitro

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.603538

DOI=10.3389/fendo.2020.603538

ISSN=1664-2392

ABSTRACT=<p>We recently characterized two paralogs of the thyrotropin (TSH) beta subunit in Atlantic salmon, <italic>tshβa</italic> and <italic>tshβb</italic>, issued from teleost-specific whole genome duplication. The transcript expression of <italic>tshβb</italic>, but not of <italic>tshβa</italic>, peaks at the time of smoltification, which revealed a specific involvement of <italic>tshβb</italic> paralog in this metamorphic event. <italic>Tshβa</italic> and <italic>tshβb</italic> are expressed by distinct pituitary cells in salmon, likely related to TSH cells from the <italic>pars distalis</italic> and <italic>pars tuberalis</italic>, respectively, in mammals and birds. The present study aimed at investigating the neuroendocrine and endocrine factors potentially involved in the differential regulation of <italic>tshβa</italic> and <italic>tshβb</italic> paralogs, using primary cultures of Atlantic salmon pituitary cells. The effects of various neurohormones and endocrine factors potentially involved in the control of development, growth, and metabolism were tested. Transcript levels of <italic>tshβa</italic> and <italic>tshβb</italic> were measured by qPCR, as well as those of growth hormone (<italic>gh</italic>), for comparison and validation. Corticotropin-releasing hormone (CRH) stimulated <italic>tshβa</italic> transcript levels in agreement with its potential role in the thyrotropic axis in teleosts, but had no effect on <italic>tshβb</italic> paralog, while it also stimulated <italic>gh</italic> transcript levels. Thyrotropin-releasing hormone (TRH) had no effect on neither <italic>tshβ</italic> paralogs nor <italic>gh</italic>. Somatostatin (SRIH) had no effects on both <italic>tshβ</italic> paralogs, while it exerted a canonical inhibitory effect on <italic>gh</italic> transcript levels. Thyroid hormones [triiodothyronine (T3) and thyroxine (T4)] inhibited transcript levels of both <italic>tshβ</italic> paralogs, as well as <italic>gh</italic>, but with a much stronger effect on <italic>tshβa</italic> than on <italic>tshβb</italic> and <italic>gh.</italic> Conversely, cortisol had a stronger inhibitory effect on <italic>tshβb</italic> than <italic>tshβa</italic>, while no effect on <italic>gh</italic>. Remarkably, insulin-like growth factor 1 (IGF1) dose-dependently stimulated <italic>tshβb</italic> transcript levels, while it had no effect on <italic>tshβa</italic>, and a classical inhibitory effect on <italic>gh</italic>. This study provides the first data on the neuroendocrine factors involved in the differential regulation of the expression of the two <italic>tshβ</italic> paralogs. It suggests that IGF1 may be involved in triggering the expression peak of the <italic>tshβb</italic> paralog at smoltification, thus representing a potential internal signal in the link between body growth and smoltification metamorphosis.</p>