Eel kisspeptins : identification, functional activity, and inhibition on both pituitary LH and GnRH receptor expression.
Pasquier J, Lafont AG, Denis F, Lefranc B, Dubessy C, Moreno-Herrera A, Vaudry H, Leprince J, Dufour S, Rousseau K. 2018. Frontiers in Endocrinology 8:353. doi: 10.3389/fendo.2017.00353
The European eel (Anguilla anguilla) presents a blockade of sexual maturation at a pre-pubertal stage due to a deficient production of gonadotropins. We initiated, in the eel, the investigation of the kisspeptin (Kp), one of the major gatekeepers of puberty in mammals and identified two genes encoding Kp (Kiss1 and Kiss2) instead of one in mammals. This study was continued in the frame of NEMO « Neuropeptides in Marine Organisms » ANR, in collaboration with the European Institute of Peptides (Rouen). Here, we cloned and sequenced Kiss1 and Kiss2 cDNAs from the eel brain. The tissue distributions of their transcripts showed that both genes are primarily expressed in the eel brain and pituitary. The sequences of predicted mature peptides in the eel, Kp1(15aa) and Kp2(12aa), as well as the two 10 aa long sequences, Kp1(10) and Kp2(10) characteristic of kisspeptin, were synthesized and functionally analyzed. Using rat Kp receptor-transfected CHO cells, we found that the four synthesized eel peptides were able to bind mammalian receptor, and to activate calcium intracellular signaling pathways. In primary culture of eel pituitary cells, all four peptides were able to specifically and dose-dependently inhibit lhb expression, without any effect on fshb. Furthermore, all four peptides inhibited the expression of a GnRH receptor (gnrh-r2). Our finding suggests that, in the eel, kisspeptins exert a a double inhibitory control, by decreasing lhb expression directly at the pituitary level, and also by reducing pituitary sensitivity to GnRH by down-regulating GnRH receptor expression. The kisspeptin system may thus contribute to the strong inhibitory control of puberty observed in the European eel. This inhibition in the eel contrasts with the stimulatory role of kisspeptin in the control of reproduction in mammals, and reveals important variations of functional role of the kisspeptin system in vertebrates despite a strong molecular conservation.
Contact BOREA: Karine Rousseau, Assistant professor MNHN
