Pituitary and hypothalamic hormones as precursor molecules of neuropeptides

The behaviorally active meiety of ACTH resides in only a few amino acid residues and is independent of its peripheral endocrine effects. Although pituitary hormones may reach the brain through the circulation and by retrograde transport through the portal vessel system, the recent discovery that ACTH as part of a big precursor molecule, pro-opiomelanocortin, is widely distributed throughout the brain suggests that "brain borne" ACTH may be the main supplier of behaviorally active neuropeptides. The biotransformation of pro-opiomelanocortin in the anterior pituitary differs from that in the intermediate/posterior lobe and the brain. Thus, the biotransformation of hormones at the site of release may determine their ultimate function i.e. as a hormone (pituitary) or as a neuropeptide (brain). Structure activity studies, and studies on the biotransformation of ACTH in brain synaptosomes corroborate the hypothesis that ACTH in the brain is a precursor of the second order of neuropeptides involved in adaptive behavior. A great number of studies in a variety of behavioral paradigms has shown that ACTH neuropeptides are involved in (visual) attention and motivation, vigilance and learning and maintenance behavior. Other pro-opiomelanocortin molecules such as beta-endorphin undergo a similar processing. Structure activity studies and biotransformation studies of this hormone have revealed the generation of neuropeptides with neuroleptic-like and psychostimulant properties. The neurohypophyseal hormones vasopressin and oxytocin appear to function as precursor molecules of the second order of potent neuropeptides involved in memory processes. The same may hold for other "brain borne" hormones.