Origin of INSL3-mediated testicular descent in therian mammals

Pair of critical substitutions at the A chain ablates LGR8-activation activity of AncRFLC. (A) Sequence comparison and identification of radical substitutions in the mammalian RLN3 A chain. Two pairs of radical substitutions in mammalian RLN3 and platypus RFLCI (asterisks). Spatial positions of these critical residues are shown (right). In the structure model, residues belong to the B and A chains are indicated by white and blue space balls, respectively. (B,C) LGR7 (RXFP1)- and LGR8 (RXFP2)-activation activities of AncRFLC, AncRFLC VV^A3,4LA, and AncRFLC NA^A8,9SS peptides (B), and RLN3 LA^A3,4VV and RLN3 SS^A8,9NA peptides (C). Mean ± SEM, N = 4.