Loss of function in somatostatin receptor 5 has no impact on the growth of medaka fish due to compensation by the other paralogs

BOAN A; DELGADIN T; CANOSA LF; FERNANDINO JI

General and Comparative Endocrinology

Academic Press Inc.

Lugar: Nueva York; Año: 2024 vol. 351

Somatic growth in vertebrates is regulated endocrinologically by the somatotropic axis, headed by the growthhormone (GH) and the insulin growth factor-I (IGF-I). Somatostatin (Sst), a peptide hormone synthesized in thehypothalamus, modulates GH actions through its receptors (Sstr). Four Sstr subtypes (Sstr 1–3 and 5) have beenidentified in teleosts. However, little is known about whether they have a specific function or tissue expression.The aim of this study was to determine the role of sstr2 and sstr5 in the growth of the medaka (Oryzias latipes).The assessed expression pattern across diverse tissues highlighted greater prevalence of sstr1 and sstr3 in brain,intestine and muscle than in pituitary or liver. The expression of sstr2 was high in all the tissues tested, while sstr5was predominantly expressed in the pituitary gland. A CRISPR/Cas9 sstr5 mutant with loss of function (sstr5-/-)was produced. Assessment of sstr5-/- indicated no significant difference with the wild type regarding growthparameters such as standard length, body depth, or peduncle depth. Furthermore, the functional loss of sstr5 hadno impact on the response to a nutritional challenge. The fact that several sstr subtypes were upregulated indifferent tissues in sstr5-/- medaka suggests that in the mutant fish, there may be a compensatory effect on thedifferent tissues, predominantly by sstr1 in the liver, brain and pituitary, with sstr2 being upregulated in pituitaryand liver, and sstr3 only presenting differential expression in the brain. Analysis of the sstr subtype and the sstr5-/-fish showed that sstr5 was not the only somatostatin receptor responsible for Sst-mediated Gh regulation.