Knockout of somatostatin receptor 5 has no effect on medaka growth

BOAN A; DELGADIN T; CANOSA LF; FERNANDINO JI

Querétaro

Congreso; NASCE 7th Biennial Meeting; 2023

North American Society for Comparative Endocrinology (NASCE)

In vertebrates,somatic growth is regulated by the somatotropic axis. It is well knownthat the primary hormone in the axis is the growth hormone (GH), which issynthesized in the pituitary gland and induces the expression of insulin-likegrowth factor I (IGF-I) in the liver, which is ultimately responsible forpromoting tissue growth and differentiation. In fish, the release of GH isunder constant negative regulation, mainly by the hormone somatostatin (SST).This hormone is synthesized in the hypothalamus of all vertebrates and acts asan inhibitor of GH secretion in the pituitary. In turn, the action of SST iscarried out through its receptors. In fish, 4 SST receptors (SSTR 1-3 and 5) havebeen described, with SSTR 2 and 5 showing the highest expression in thepituitary gland. Therefore, we hypothesized that blocking this inhibition producesan increase in GH secretion, with concomitant somatic growth. We tested this by generating an SSTR 5 mutant usingthe CRISPR/Cas9 system. First, we analyzed the effect of loss of function on medakagrowth by performing a growth experiment in which we breed knock-out fish andWT fish from the hatch and measure the standard length every week until week 7.We observe that the knockoutsdo not growsignificantly faster than the WT fish . We then evaluated whether the SSTR 5 is involved incompensatory growth. Comparing WT fish after a short-term fasting exposure withnormal-fed WT fish, we observe a differential expression of GH but nodifference in the somatostatin or its receptors (SSTR5). When we performed afasting test with the knockouts, we did not observe a significant variation in bodyweight between the feeding protocols. Taken together, the results suggest thatthe SSTR 5 is not the only somatostatin receptor mediating the SST-GHinteraction and is not, or at least not acting alone, for the changes incompensatory growth. [FC1]No me gusta