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Overview of Fish Growth Hormone Family. New Insights in Genomic Organization and Heterogeneity of Growth Hormone Receptors

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Abstract

Growth hormone (GH), prolactin (PRL) and somatolactin (SL) are single chain proteins structurally and functionally related. Fish PRL and GH receptors (PRLR, GHR) have been characterized in several fish species. There is limited evidence of fish PRLR isoforms, but emerging data support the existence of different GHR variants. In gilthead sea bream, black sea bream, turbot and fugu, but not in zebrafish, GHR has retained an exclusive fish intron (10/10A). In gilthead sea bream and turbot, this intron is not alternatively spliced, but the black sea bream intron is either removed or retained during mRNA processing, resulting in a long GHR isoform with a 31 amino acid insertion that does not alter the open reading frame. This or any other GHR variant are not found in gilthead sea bream, but a truncated anchored form has been reported in turbot. The latter GHR isoform comprises extracellular and trans-membrane domains, the first 28 amino acids of the intracellular domain and 21 divergent amino acids before a stop codon. This GHR variant is the result of alternative splicing, being the 3′ UTR and the divergent sequence identical to the sequence of the 5′ end of the 9/10 intron. The physiological significance of different fish GHR isoforms remains unclear, but emerging data provide suitable evidence for season and nutrition related changes in the somatototropic axis activity. The up-regulation of circulating GH together with the decrease of plasma titres of insulin-like growth factor-I (IGF-I), an altered pattern of serum IGF binding proteins and a reduced expression of hepatic IGF-I and GHRs represent a mechanism conserved through vertebrate evolution. It secures the preferential utilization of mobilized substrates to maintain energy homeostasis rather than tissue growth. Somatolactin also changes as a function of season, ration size, dietary amino acid profile and dietary protein source creating opposite plasma GH and SL profiles. There is now direct evidence for a lipolytic effect of fish SL, acting at the same time as an inhibitory factor of voluntary food intake. Indeed, long-term feeding restriction results in the enlargement of the summer GH peak, whereas the SL rise coincident with shortened day length is delayed in juvenile fish until late autumn. These findings agree with the idea that SL may act as a marker of energy surplus, priming some particular process such as puberty onset. However, it remains unclear whether SL works through specific receptors and/or dimers or heterodimers of GH and PRL receptors.

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Pérez-Sánchez, J., Calduch-Giner, J., Mingarro, M. et al. Overview of Fish Growth Hormone Family. New Insights in Genomic Organization and Heterogeneity of Growth Hormone Receptors. Fish Physiology and Biochemistry 27, 243–258 (2002). https://doi.org/10.1023/B:FISH.0000032729.72746.c8

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