SUMMARYThe velvet belly lantern shark (Etmopterus spinax) emits a blue luminescence from thousands of tiny photophores. In this work, we performed a pharmacological study to determine the physiological control of luminescence from these luminous organs. Isolated photophore-filled skin patches produced light under melatonin (MT) and prolactin (PRL) stimulation in a dose-dependent manner but did not react to classical neurotransmitters. Theα-melanocyte-stimulating hormone (α-MSH) had an inhibitory effect on hormonal-induced luminescence. Because luzindole and 4P-PDOT inhibited MT-induced luminescence, the action of this hormone is likely to be mediated through binding to the MT2 receptor subtype, which probably decreases the intracellular concentration of cyclic AMP (cAMP) because forskolin (a cAMP donor) strongly inhibits the light response to MT. However, PRL seems to achieve its effects via janus kinase 2 (JAK2) after binding to its receptor because a specific JAK2 inhibitor inhibits PRL-induced luminescence. The two stimulating hormones showed different kinetics as well as a seasonal variation of light intensity, which was higher in summer (April) than in winter (December and February). All of these results strongly suggest that,contrary to self-luminescent bony fishes, which harbour a nervous control mechanism of their photophore luminescence, the light emission is under hormonal control in the cartilaginous E. spinax. This clearly highlights the diversity of fish luminescence and confirms its multiple independent apparitions during the course of evolution.