KNOCKOUT OF SOMATOSTATIN RECEPTOR 5 HAS NO EFFECT ON MEDAKA GROWTH

BOAN, A.; DELGADIN, T.H.; CANOSA, L.F.; FERNANDINO, J.I.

Congreso; 7th Biennial Meeting of the North American Society for Comparative Endocrinology; 2023

North American Society for Comparative Endocrinology

In vertebrates, somatic growth is regulated by the somatotropic axis. It is well known that the primary hormone in the axis is the growth hormone (GH), which is synthesized in the pituitary gland and induces the expression of insulin-like growth factor I (IGF-I) in the liver, which is ultimately responsible for promoting tissue growth and differentiation. In fish, the release of GH is under constant negative regulation, mainly by the hormone somatostatin (SST). This hormone is synthesized in the hypothalamus of all vertebrates and acts as an inhibitor of GH secretion in the pituitary. In turn, the action of SST is carried out through its receptors. In fish, 4 SST receptors (SSTR 1-3 and 5) have been described, with SSTR 2 and 5 showing the highest expression in the pituitary gland. Therefore, we hypothesized that blocking this inhibition produces an increase in GH secretion, with concomitant somatic growth. We tested this by generating an SSTR 5 mutant using the CRISPR/Cas9 system. First, we analyzed the effect of loss of function on medaka growth by performing a growth experiment in which we breed knock-out fish and WT fish from the hatch and measure the standard length every week until week 7. We observe that the knockouts do not grow significantly faster than the WT fish. We then evaluated whether the SSTR 5 is involved in compensatory growth. Comparing WT fish after a short-term fasting exposure with normal-fed WT fish, we observe a differential expression of GH but no difference in the somatostatin or its receptors (SSTR5). When we performed a fasting test with the knockouts, we did not observe a significant variation in body weight between the feeding protocols. Taken together, the results suggest that the SSTR 5 is not the only somatostatin receptor mediating the SST-GH interaction and is not, or at least not acting alone, for the changes in compensatory growth.