Somatostatin 4 regulates growth and modulates gametogenesis in zebrafish

Somatostatin (SST) plays important roles in growth and development. In teleost fishes six SST encoding genes (sst1 to sst6) have been identified although few studies have addressed their function. Here we aim to determine the function of the teleost specific sst4 in the zebrafish. A CRISPR/Cas9 sst4 zebrafish mutant with loss of function (sst4−/−) was produced which grew significantly faster and was heavier at the onset of gonadal maturation than the wild type (WT). Consistent with their faster growth, liver igf1, igf2a and igf2b expression was significantly upregulated in the sst4−/− fish compared to the WT. Histological examination of the ovaries and testis indicated that sst4−/− fish had slightly delayed testicular gametogenesis compared to the WT. Significantly lower expression of igf3, amh, insl3, hsd17b3, hsd11b2, hsd20b, cyp11b and cyp17 was consistently observed in the sst4−/− testis. In contrast, the ovaries had lower expression of igf1, igf2a and cyp19a1a but increased expression of igf2b and hsd20b. The gonadotrophin beta subunits (fshb and lhb) in the brain were downregulated indicating the brain-pituitary-gonadal axis was downregulated in the sst4−/− fish and suggesting that the steroid production is compromised in the maturing gonads. In addition, analysis of sst1 and sst3 mRNA levels in sst4−/− fish suggests a dosage compensation effect of sst1 in the brain and liver. Altogether, the results from the zebrafish sst4−/− line support the idea that sst4 is involved in the regulation of igf signalling, somatic growth and reproduction since steroidogenesis and gametogenesis at pubertal onset were compromised. Keywords: Somatostatin 4, Gametogenesis, Zebrafish, Gonadotrophin, Puberty