Effect Of Prolactin-releasing Peptide Research Articles

Prolactin-releasing peptide increases rat anxiety

Prolactin-releasing peptide(Prl-RP), in addition to stimulating the production of prolactin, interacts with various parts of the central nervous system, participating in the implementation of many functions that are reflected in behavior. The effect of Prl-RP on the anxiety of white Wistar rats was studied since there were no data in the literature on the relationship between Prl-RP and anxiety. Anxiety was assessed in two tests. In the elevated plus-maze (EPM), the time spent in the open arms and the number of edge reactions were recorded. In the social preference test, the time spent near a stranger, near a familiar individual, and in neutral territory were recorded. The administration of Prl-RP at a dose of 10-10 M with a volume of 10 µl in each nostril reduced the time spent by the animals in the open arms of the EPM, and the number of edge reactions. For testing the social interaction, animals were pre-selected for high or low levels of anxiety in the EPM. In rats with initially low levels of anxiety, Prl-RP reduced the time spent near a stranger, indicating an increase in anxiety levels. The behavior of rats with initially high levels of anxiety did not change after application of the Prl-RP. The results of our experiments indicate that the intranasal administration of Prl-RP increases the anxiety of rats.

Effects of prolactin-releasing peptide on food intake and metabolism

Effects of prolactin-releasing peptide on food intake and metabolism

Abstract 387: Prolactin-Releasing Peptide, the Novel Endogenous Ligand of the Orphan Receptor GPR10, Regulates Cardiac Contractility

The hypothalamic prolactin-releasing peptide (PrRP), which is the endogenous ligand of the orphan receptor GPR10, plays an important role in the regulation of the central stress response, sleep regulation and feeding behavior. Although specific binding sites have been found in the rat myocardium, the functional importance of PrRP in the regulation of cardiovascular system is still unknown. The objective of the present study was to characterize the direct cardiac effects of PrRP as well as the underlying signaling mechanisms. In the isolated perfused, paced rat heart preparation (male 7-week-old, Sprague-Dawley rats, n=138), intracoronary infusion of PrRP-31 (1–30 nmol/L) for 15 min induced a dose-dependent, slowly developing positive inotropic effect, with a maximal increase in developed tension at the dose of 10 nmol/L (13.6%±3.1, P< 0.001). Next we tested if various counter-regulatory mechanisms could modify the effect of PrRP. The phosphodiesterase inhibitor IBMX (10 μmol/L) failed to alter the inotropic response to PrRP (10.7±1.9%, P=N.S.) excluding the involvement of cAMP-dependent mechanisms. In contrast, the specific protein kinase C-alfa (PKC-alpha) inhibitor Ro32– 0432 (100 nmol/L) significantly increased the inotropic response to PrRP (21.6±3.4%, P<0.05) as well as the phosphorylation of phospholamban at Ser-16 (1.5±0.09 vs. 1.0±0.18; P<0.001) as measured by Western blotting. Moreover, the protein phosphatase (PP1/PP2A) inhibitor calyculin A (CyA) augmented the effect of PrRP on contractility (20.7 ±1.7%, P<0.001) similarly to PKC-alpha inhibition, whereas the PP2A inhibitor okadaic acid (10 nmol/L) had no effect (7.8±1.0 %, P=N.S.). Furthermore, long-term (120 min) administration of PrRP resulted in a greater increase in contractility (20.3±3.1 %) as compared to short-term infusion (15 min; P<0.05). Our results provide the first evidence for the functional significance of PrRP in the heart. The positive inotropic effect of PrRP is mediated via cAMP-independent mechanisms, which are suppressed by enhanced activity of PKC-alpha and PP1. We suggest that PrRP may play an important role in the long-term regulation of myocardial contractility.

Prolactin-releasing peptide (PrRP) increases prolactin responses to TRH in vitro and in vivo

The Prolactin-releasing Peptide (PrRP) is a 31-aminoacid peptide produced and secreted from the hypothalamus, and postulated to promote the prolactin release from the pituitary. However, the action of PrRP remain controversial, since it was described to have potency comparable enough to TRH, although there are many evidences that PrRP is less potent than TRH. Here we have studied the effects of PrRP alone or in combination with TRH in the prolactin levels of rat pituitary primary cell cultures in vitro and also in vivo prolactin responses in randomly cycling and estrogens-treated female rats. PrRP itself increased prolactin levels in vitro and in vivo, although in a magnitude several times lower than TRH. In vivo PrRP promotes an atypical non-peaking progressive and maintained prolactin increase. On the other hand, PrRP markedly increased the prolactin responses to TRH in vitro (10-30 fold increase) and in vivo (up to three-fold increase). In addition, FGF-2 and EGF, two important growth factors present in the pituitary, reduced the PrRP-induced prolactin increase in vitro. Taken together our results suggest that PrRP released from the hypothalamus may be relevant to modulate the circulating prolactin levels in the rat.

Expression of prolactin-releasing peptide and its receptor in the human decidua.

Human decidua and decidualized endometrial cells produce prolactin (PRL). Several growth factors and cytokines have been shown to regulate decidual PRL release, but a specific PRL-releasing substance remains to be characterized. Prolactin-releasing peptide (PrRP) is a peptide isolated from the brain and distinguished by its potent and specific stimulation of PRL release by cultured pituitary cells. Here, we demonstrate that human decidua expresses immunoreactive PrRP as well as the mRNAs encoding PrRP and its receptor. First trimester deciduas were obtained from women undergoing elective termination of pregnancy. Tissue specimens were stained by immunohistochemistry using a rabbit anti-human PrRP-31 antibody, and PrRP was localized in both epithelial cells of the decidual glands and in stromal cells, with diffuse distribution and no special relation with the neighbourhood of blood vessels. In primary cultures of decidual stromal cells, PrRP and PrRP receptor gene expression were detected using RT-PCR, and the identity of the PCR products was further confirmed by restriction enzyme digestion. The effect of PrRP on decidual PRL release was also evaluated, and there was a significant increase in PRL production (135 +/- 4% of control levels, P < 0.05) after incubation of decidual stromal cells with synthetic PrRP. The expression of PrRP and PrRP receptor in human decidual cells and the ability of PrRP to induce PRL secretion by cultured decidual cells suggests that this peptide may be a novel local modulator of decidual PRL release.

Effects of Prolactin-Releasing Peptide on Tuberoinfundibular Dopaminergic Neuronal Activity and Prolactin Secretion in Estrogen-Treated Female Rats

Both systemic and central effects of a newly discovered prolactin (PRL)-releasing factor (PRF), prolactin-releasing peptide (PrRP), were determined in this study. Systemic injection of PrRP (1 and 10 µg/rat, i.v.) stimulated PRL secretion in ovariectomized, estrogen-treated rats similar to the effect of another PRF, thyrotropin-releasing hormone (TRH). Pretreatment with a dopamine D₂ receptor antagonist, sulpiride (1 µg/rat, i.v.), potentiated the stimulatory effect of both PrRP and TRH on PRL secretion. Using the double-labeling immunohistochemical method, PrRP-immunoreactive terminals were found in close contact with tyrosine-hydroxylase-immunoreactive neurons in the hypothalamic arcuate nucleus. Central administration of PrRP (0.1–1,000 ng/rat, i.c.v.) stimulated tuberoinfundibular but not nigrostriatal dopaminergic neuronal activity in 15 min. Levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence and striatum were used as indices for tuberoinfundibular dopaminergic (TIDA) and nigrostriatal dopaminergic neuronal activities, respectively. The serum PRL level, however, was not significantly changed. Similar treatment with TRH (10 ng/rat, i.c.v.) stimulated and inhibited TIDA neuronal activity and serum PRL, respectively, at 30 min. In summary, PrRP may play a role in both the central and peripheral control of PRL secretion.

Effects of prolactin-releasing peptide on tuberoinfundibular dopaminergic neuronal activity and prolactin secretion in estrogen-treated female rats.

Both systemic and central effects of a newly discovered prolactin (PRL)-releasing factor (PRF), prolactin-releasing peptide (PrRP), were determined in this study. Systemic injection of PrRP (1 and 10 microg/rat, i.v.) stimulated PRL secretion in ovariectomized, estrogen-treated rats similar to the effect of another PRF, thyrotropin-releasing hormone (TRH). Pretreatment with a dopamine D2 receptor antagonist, sulpiride (1 microg/rat, i.v.), potentiated the stimulatory effect of both PrRP and TRH on PRL secretion. Using the double-labeling immunohistochemical method, PrRP-immunoreactive terminals were found in close contact with tyrosine-hydroxylase-immunoreactive neurons in the hypothalamic arcuate nucleus. Central administration of PrRP (0.1-1,000 ng/rat, i.c.v.) stimulated tuberoinfundibular but not nigrostriatal dopaminergic neuronal activity in 15 min. Levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence and striatum were used as indices for tuberoinfundibular dopaminergic (TIDA) and nigrostriatal dopaminergic neuronal activities, respectively. The serum PRL level, however, was not significantly changed. Similar treatment with TRH (10 ng/rat, i.c.v.) stimulated and inhibited TIDA neuronal activity and serum PRL, respectively, at 30 min. In summary, PrRP may play a role in both the central and peripheral control of PRL secretion.

Local production and action of prolactin-releasing peptide (PrRP) in human decidua.

Objective: The human decidua is a source and target of prolactin (PRL), whose secretion is modulated by several unspecific molecular mechanisms. Prolactin-Releasing Peptide (PrRP) is a peptide recently isolated from the brain and characterized by a potent and specific stimulation of PRL release from pituitary cells. The present study investigated the expression of PrRP and its receptor in the decidua, and the effect of PrRP on decidual PRL release was evaluated as well.

Analyses for susceptibility of rat anterior pituitary cells to prolactin-releasing peptide.

We validated the effect of prolactin-releasing peptide (PrRP) on prolactin (PRL) secretion from rat anterior pituitary cells in in vitro culture. We found that culture conditions considerably influenced the response of the anterior pituitary cells to PrRP. Longer culture term (4 d) was required to obtain better responses of the anterior pituitary cells to PrRP in comparison to thyrotropin-releasing hormone (TRH). Under the culture conditions employed here, PrRP was comparable to TRH in the potency promoting PRL secretion, and the action of PrRP was very specific for PRL secretion. The susceptibility of the anterior pituitary cells to PrRP varied in female rats depending on the process of reproduction: the cells prepared from lactating rats were the most sensitive to PrRP compared with those from random-cycle and pregnant rats. Because the expression levels of PrRP receptor mRNA in the pituitary varied during the reproductive process, we speculated that the susceptibility of the anterior pituitary cells would reflect cellular changes including the expression level of PrRP receptors. In addition, treatment with estrogen in vivo enhanced the susceptibility of the cultured anterior pituitary cells in male rats. Our results indicate that the susceptibility of the rat anterior pituitary cells to PrRP is regulated by physiological mechanisms.

Stimulation of Prolactin Release by Prolactin-Releasing Peptide in Rats

We have previously reported a hypothalamic peptide that shows specific prolactin (PRL)-releasing activity in vitro, named prolactin-releasing peptide (PrRP). However, its activity in vivo has not yet been shown. In this study, we examined whether PrRP could induce specific PRL release in vivo using normal cycling female and male rats. Intravenous injection of PrRP31 increased plasma PRL levels in rats in a dose-dependent manner. PrRP31 (50 nmol/kg i.v.) significantly (P < 0.05) stimulated plasma PRL levels within 25 min after injection in rats in proestrus, estrus, and metestrus. A higher dose of PrRP31 (500 nmol/kg i.v.) was necessary for a significant increase in plasma PRL levels in male rats. These results clearly indicate that female rats, especially at proestrus, are more sensitive to PrRP-induced PRL secretion than male rats. The effect of PrRP on PRL release is affected considerably by the estrous cycle and sex, which suggests that PrRP sensitivity is controlled by the endogenous hormonal milieu, such as estrogen levels. PrRP31 did not affect other pituitary hormone secretions. The results indicate that PrRP shows specific PRL-releasing activity in vivo as well as in vitro and suggest that it plays an important role in the regulation of PRL release under certain physiological conditions.