Neurotensin gene expression has been shown to be modulated by estrogen in both human SK-N-SH neuroblastoma cell cultures as well as in mice through interactions with cyclic AMP (cAMP) signaling. Specifically, estrogen increased cAMP activity and cAMP response element-binding protein phosphorylation in neuroblastoma cells prior to the induction of neurotensin gene transcription. Additionally, neurotensin gene transcription was blocked in knock-out mice lacking the RIIβ subunit of the protein kinase A holoenzyme. These findings may indicate mechanisms of cross-talk signaling in brain hormone activity and expression of hormone-related genes. Other sex hormone-related changes in neurotensin expression have been associated with activity in the preoptic area. In female rats, neurotensin expression was shown to be at its highest in the medial preoptic area (mPOA) during the proestrus phase of the estrous cycle.