It should be pointed out that there is an notable controversy concerning the role of GPER1 as the principal mediator of the estrogen response in vivo, because even though nuclear receptors are less expressed in melanoma than GPER1 (Median level for GPER1 = 1.86; Erα = 0.61; Erβ = 0.31Tpm according to TCGA data base), they have a higher affinity for 17β-estradiol (GPER1 = 3–6 nM and ERs = 0.1–1 nM) [97]. Here, GPER1 is linked to melanoma.