Prolactin‐Releasing Peptide is Expressed in Afferents to the Endocrine Hypothalamus, but not in Neurosecretory Neurones

Abstract

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.

The prolactin releasing peptides: RF-amide peptides

“…This is the site where recognized releasing and inhibiting factors of hypothalamic origin gain access to the hypophysial portal vasculature and the anterior lobe. Instead, PrRP immunoreactive neurons in medulla have been identified by retrograde labeling to project to the paraventricular nucleus of the hypothalamus [40]. Furthermore, the number of PrRP neurons does not differ in the medulla of brains from male, nonpregnant female and pregnant female rats [40], and the distribution of PrRP immunoreactive fibers does not change during the estrous cycle [31].…”

“…Instead, PrRP immunoreactive neurons in medulla have been identified by retrograde labeling to project to the paraventricular nucleus of the hypothalamus [40]. Furthermore, the number of PrRP neurons does not differ in the medulla of brains from male, nonpregnant female and pregnant female rats [40], and the distribution of PrRP immunoreactive fibers does not change during the estrous cycle [31]. Finally, Lawrence and co-workers [42] have reported that expression of PrRP apparently decreases in lactation and fasting, suggesting a role for the peptide related to energy homeostasis and not the neuroendocrine regulation of PRL secretion.…”

“…It is possible that the peptide content of adrenal gland reported by Matsumoto [40] reflected peptide bound to the receptor. This peptide may have originated in plasma (source of production unknown) or it may have been delivered by the nerves innervating the chromaffin cells of the adrenal medulla.…”

“…Only scant fibers project to the basal hypothalamus, including the median eminence, and little staining was observed in the posterior pituitary gland. Several groups have identified the medullary cells expressing PrRP also to be tyrosine hydroxylase positive, for example the A2 and A1 noradrenergic cell groups [34,35,40], suggesting cosecretion of peptide and catecholamine within the brain. The projection fibers staining positive for PrRP terminate in brain regions that express abundant mRNA for the PrRP receptor [34,46].…”

Functions of Two Distinct “Prolactin-Releasing Peptides” Evolved from a Common Ancestral Gene

“…In the rat brain, PrRP nerve cell bodies are distributed in the hypothalamic dorsomedial nucleus (DMN), the nucleus of the solitary tract (NTS), and ventral and lateral reticular nuclei (VLRN) in the medulla oblongata (31–33). PrRP neurons in the VLRN and NTS are considered to be A1 and A2 noradrenergic neurons, respectively (34, 35). PrRP nerve fibers project to several brain regions, such as the bed nucleus of the stria terminalis, hypothalamic paraventricular nucleus (PVN), hypothalamic periventricular nucleus (PerVN), and basolateral amygdaloid complex (31, 36).…”