Decreased activity of the melanocortin system in zabrafish enhances growth during early adulthood but has no impact in puberty

Abstract

In two swordtail species of the genus Xiphophorus, onset of puberty in males and females, fecundity in females, and adult size in males are modulated by sequence polymorphism and gene copy-number variation at the P locus affecting the type 4 melanocortin hormone receptor (Mc4r). The involvement of Mc4r in regulating the onset of puberty outside the genus Xiphophorus remains unclear. Mc4r binds the melanocyte-stimulating hormones (Mshs) and two inverse agonists, agouti-related protein (Agrp) and agouti-signalling protein (Asip). Both Agrp and Asip inhibit the constitutive activity of Mc4r and antagonistically compete with α-Msh. We used a transgenic line overexpressing asip1 (asip1-Tg), to investigate the relevance of the melanocortin system on the onset of puberty and adult reproductive performance in the zebrafish (Danio rerio). By comparing wild-type (WT) and asip1-Tg zebrafish we show that a decreased activity of the melanocortin system does not change the timing of puberty but significantly delays early growth of transgenic animals. Hatching time is postponed in asip1-Tg fish and they are significantly smaller than their WT siblings at 75 dpf, despite showing enhanced linear growth after having completed puberty. Even though asip1-Tg females spawn less frequently they produce 1.38 times more eggs that are smaller in diameter but render larvae with a 1.04-fold increase in body length at hatching. We demonstrate that the decreased activity of the melanocortin system induced by asip overexpression does not accelerate the puberty timing but significantly delays early growth of transgenic animals. Once asip-tg animals have outperformed a threshold length, when puberty has already been reached, the transgene rapidly promotes linear growth in absence of obesity