THE NEUROHYPOPHYSEAL ENDOCRINE REGULATORY CASCADE - PRECURSORS, MEDIATORS, RECEPTORS, AND EFFECTORS

The neurohypophysial endocrine regulatory cascade has been described a s a molecular model of neuroendocrine control of organismal functions. Any physiological function can be analyzed in molecular terms as a su ccession of interactions occurring either in a solution or in a membra ne system. The key mechanism in the ordering of the cascade is the con formational recognition of the two partners at each step. Each interac tion results in a change of conformation of a recognized protein that in turn becomes a recognizer for the following molecule. The cascade s tarts within the secretory cell by the processing of the expressed pre cursor along the secretory pathway until the storage of the mature med iator in vesicles and its subsequent exocytic secretion in blood. The circulating mediator recognizes the target cell through specific membr ane receptors that transduce the message within this target cell. A se cond intracellular cascade leads to activation of the effector, the pr otein fulfilling the physiological function. The complexity of the mes sages is, in part, due to the duplication propensity of the genomic DN A, the frequent occurrence of multiple copies for precursors, mediator s, receptors, and effecters, and therefore, a combinatorial diversity that increases during the course of evolution. Vertebrate neurohypophy sial hormones can be ordered in two main evolutionary lineages, culmin ating in oxytocin and vasopressin in placental mammals. In this field, diversification of the messages was made by differential processing o f the precursors, secondary gene duplications, the emergence of severa l types of receptors for each hormone, and a variety of effecters trig gered by the second messengers within differentiated target cells. Thi s review is an attempt to integrate neurohypophysial functions at the molecular, cellular, and organismal levels. (C) 1995 Academic Press, I nc.