GHR and hepatocellular carcinoma: Activation of these enzymes and increases in intracellular cAMP have critical roles in alkalinization of intracellular pH by reactivating NHEs.[27] Additionally, it has been shown that PKA activation and increased cAMP mediate TH effects such as increased growth hormone receptor signaling in cancer cells.[28,29] T3 may increase sensitivity to growth hormones by inducing PKA activation and cAMP increases in hepatocytes, thereby indirectly contributing to the development and progression of HCC.