Prolactin-Releasing Peptide and Its Homolog RFRP-1 Act in Hypothalamus but Not in Anterior Pituitary Gland to Stimulate Stress Hormone Secretion

Abstract

The RF-amide peptides (RFRPs), including prolactin (PRL)-releasing peptide-31 (PrRP-31) and RFRP-1, have been reported to stimulate stress hormone secretion by either direct pituitary or indirect hypothalamic actions. We examined the possible direct effects of these peptides on PRL and adrenocorticotropin (adrenocorticotropic hormone [ACTH]) release from dispersed anterior pituitary cells in culture and on PRL and ACTH secretion following intracerebroventricular (i.c.v.) administration in vivo. Neither peptide significantly altered PRL or ACTH release from cultured pituitary cells (male rat donors). Central administration of 1.0 and 3.0 nmol of PrRP-31, but only the higher dose of RFRP-1, significantly elevated serum corticosterone levels in conscious male rats. The effect of PrRP-31 was not blocked by pretreatment (i.v.) with the corticotropin-releasing hormone (CRH) antagonist, alpha-helical CRH 9-41; however, pretreatment of the animals (i.v.) with an antiserum to CRH significantly lowered the hypothalamic-pituitary- adrenal axis response to central administration of PrRP-31. On the other hand, the release of PRL was significantly elevated by 3.0 nmol of RFRP-1, but not PrRP-31, in similarly treated, conscious male rats. Pretreatment with the catecholamine synthesis inhibitor, alpha-methyl-para-tyrosine, prevented the stimulation of PRL secretion observed following central administration of RFRP-1. RFRP-1 similarly did not alter PRL secretion in rats pretreated with the dopamine, D(2) receptor blocker, domperidone. These results suggest that the RF-amide peptides are not true neuroendocrine regulators of stress hormone secretion in the rat but, instead, act centrally to alter the release of neuroendocrine factors that do act in the pituitary gland to control PRL and ACTH release. In the case of RFRP-1, stimulation of PRL secretion is potentially owing to an action of the peptide to inhibit dopamine release into the median eminence. The corticosterone secretion observed following central administration of PrRP-31 does not appear, based on our current results, to be solely owing to an action of the peptide on CRH-producing neurons but, instead, may be a result of the ability of PrRP-31 to increase as well the exposure of the corticotrophs in vivo to other ACTH secretagogues, such as oxytocin or vasopressin.

The role of RFamide peptides in feeding

“…It now appears unlikely that PrRP stimulates prolactin release in vivo (Taylor & Samson 2001), despite there being evidence that PrRP is involved in regulating the secretion of other hypothalamopituitary factors, including corticotrophin-releasing hormone, follicle-stimulating hormone (FSH) and luteinising hormone (LH), and oxytocin (Maruyama et al 1999b, Hizume et al 2000, Samson et al 2003.…”

“…Our own studies suggest that both RFRP-1 and -3 have the ability to modify feeding in rats and mice when administered centrally (unpublished observations). ICV administration of RFRP-1 to rats has also been shown to raise circulating levels of prolactin in a concentration-dependent manner, without an observable effect on circulating growth hormone (GH), LH, FSH, thyrotrophin-and adrenocorticotrophin-releasing hormone levels , Samson et al 2003. However, RFRP-1 was not able to elicit the release of prolactin from dispersed anterior pituitary cells, and its ability to increase prolactin in vivo was attenuated in rats pre-treated with the dopamine D2 receptor blocker, domperidone (Samson et al 2003).…”

A novel G protein-coupled receptor for gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica): identification, expression and binding activity

“…In mammals, Hinuma et al (2000) have found that the deduced human LPXRF-amide peptide, human RFRP-1, increased prolactin release in the rat. Another group has also reported the stimulatory effect of RFRP-1 on prolactin release (Samson et al 2003). Hinuma et al (2000) have further reported the receptors for rat and human RFRP, which were G protein-coupled receptors (GPCRs).…”

Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway

“…GPR10, also known as the prolactin releasing hormone receptor (PRLHR), is the receptor for prolactin releasing peptide (PrRP), although evidence for its specific role in pituitary PRL production is tenuous (16,17). Normal expression and function of GPR10 have been shown to be limited to several regions of the hypothalamus (18,19). The mechanism of hypothalamic GPR10 action that evokes stress hormone release (19) from the pituitary is not well understood and its function in the periphery, either in normal tissues or in disease, has not been reported.…”

“…Normal expression and function of GPR10 have been shown to be limited to several regions of the hypothalamus (18,19). The mechanism of hypothalamic GPR10 action that evokes stress hormone release (19) from the pituitary is not well understood and its function in the periphery, either in normal tissues or in disease, has not been reported. The nearubiquitous overexpression of GPR10, a normally neuronal specific G protein coupled receptor (GPCR), in human leiomyomas is unparalleled among genes shown to be dysregulated in fibroids.…”