Physiologic Role for Prolactin Releasing Peptide

Prolactin (PRL) releasing peptide (PrRP) is produced in A1 and A2 catecholaminergic neurons of the ventrolateral medulla and nucleus tractus solitarius (NTS), respectively. PrRP‐positive neurons in NTS project to the hypothalamic paraventricular and arcuate nuclei. I.c.v. administration of PrRP in conscious rats results in increased circulating PRL levels. We have developed an siRNA plasmid, which when injected bilaterally into the NTS results in significant diminution of immunoreactive PrRP content in the hypothalamus. We hypothesized that this would also impair the animal’s neuroendocrine response to restraint stress. Plasmid containing our PrRP siRNA or a control plasmid (scrambled siRNA) were injected bilaterally into the NTS of adult male rats bearing an indwelling jugular vein cannula. 18 hr later two blood samples (0 and 5 min) were withdrawn from the jugular cannula of conscious, unrestrained animals. They were then subjected to 10 min immobilization stress and additional blood samples taken during the stress (10 min) and at the end of the immobilization (15 min). The rats were then returned to their cages and two more blood samples taken at 20 and 30 min. There were no significant differences in plasma PRL levels between treatment groups before restraint (0 and 5 min). A significant, 10 fold increase in plasma PRL levels was observed in the control animals, while only a 4 fold increase in PRL was observed in siRNA treated rats. Plasma PRL levels were significantly lower in siRNA treated rats versus controls at 15, 20 and 30 min. These data demonstrate the efficacy of our plasmid based siRNA delivery system and suggest that PrRP, produced in neurons of the NTS which project to neuroendocrine centers in the hypothalamus, is an important mediator of stress related PRL secretion in the rat. Supported by NIH HL066023.