Genetic ablation of ACTH receptor induces skin hyperpigmentation in fish

XIII Congress of the Iberian Association of Comparative Endocrinology - AIEC (online), 16-17 September 2021
The melanocortin system is a complex neuroendocrine signaling mechanism involved in numerous physiological processes in vertebrates, including pigmentation, steroidogenesis and metabolic control. In humans, five melanocortin receptors (MCR) have been cloned, identified and shown to have a wide distribution throughout the body and likely many diverse functions. It has also been shown that a high degree of identity and conservation in structural characteristics and pharmacology exists between Mcrs from fish and mammals. However, in fishes, the number, affinity, specificity, tissue distribution and physiological roles are far from defined and appear to be species-specific. A clear example is the Mcr2 subtype. In humans, it is well known that Mc2r is expressed in the adrenal gland and controls steroidogenesis and the same function has also been described in fish. In human, ACTH overproduction results into hyperpigmentation because of pharmacological effects on MC1R. Using CRISPR/Cas9, we demonstrated that zebrafish lacking Mc2r shows hyperpigmentation. Ongoing studies are exploring potential direct/indirect roles for Mc2r in fish skin pigmentation
This work was funded by the Spanish Economy and Competitiveness Ministry project AGL2017-89648P to JR