MC4R and hypertensive disorder: In contrast, in female SHR, estrogens do not contribute to the hypertension (Reckelhoff et al. 1998), but the sympathetic nervous system, renal nerves, and the RAS do contribute (Yanes and Reckelhoff 2011), although sympathetic activation is not mediated by MC4R activation (Maranon et al. 2014).