Subject to the demonstration of a significant functional variation in human populations, inhibitory molecules such as SOCS-3 [232,243,244,250], PTB-1B [232,240,252]and possibly the regulator of the leptin receptor (OB-RGRP) [247,248,253] - all as negative regulators of leptin sensitivity, by their decreasing action, are candidates to increase hypothalamic sensitivity to leptin in the LHS-driven concept for AIS pathogenesis. This evidence concerns the gene LEP and androgen insensitivity syndrome.