Prolactin-releasing peptide is expressed in afferents to the endocrine hypothalamus, but not in neurosecretory neurones.

Prolactin release from the anterior pituitary is regulated principally by inhibitory influences imparted by the tuberoinfundibular dopamine system. Stimulatory control is provided by several hypothalamic, peripheral and local factors. Recently a new peptide, prolactin releasing peptide (PrRP), showing prolactin-secretagogue effects was discovered, synthesized and found to be expressed in brain. We have used histochemical and axonal transport methods to characterize the distribution of PrRP mRNA in the rat brain, and to identify possible pathways through which this factor might be delivered to the anterior lobe of the pituitary and thereby participate in the regulation of prolactin secretion. Analysis of histochemical preparations indicated that apart from a small population of cells in a non-neurosecretory portion of the hypothalamus, PrRP mRNA is expressed exclusively in the caudal part of the nucleus of the solitary tract and in the caudal ventrolateral medulla. All medullary PrRP expressing cells could be immunolabeled for tyrosine hydroxylase, and none were found to stain for glucagon-like peptide-1, identifying them as comprising subsets of A2 and A1 noradrenergic neurones, respectively. Numerous PrRP-expressing cells were retrogradely labelled following tracer injections in the paraventricular nucleus, while only a handful were backfilled following intravenous injections of tracer, indicating that this population issues substantial projections to the endocrine hypothalamus and meager ones to the median eminence and/or posterior pituitary. This conclusion was supported by the results of experiments in which the anterograde tracer, biotinylated dextran-amine, was injected into the PrRP cell group in the nucleus of the solitary tract. These findings suggest that PrRP expressing neurones display a highly restricted distribution, and are in a position to regulate the output of particular cell types in the endocrine hypothalamus. Whether and how PrRP might be delivered to the anterior pituitary remains to be determined.