Disease relevance of Prlr

• Prolactin receptor knockdown in the rat paraventricular nucleus by a morpholino-antisense oligonucleotide causes hypocalcemia and stress gastric erosion [1].
• Also, PRL-R AS treatment impaired maternal behaviour (P < 0.05), whereas physiological parameters of lactation (weight gain of the litter, number of milk ejection reflexes during a 20-min suckling period) were not affected [2].
• Cross-linking of G-proteins to the prolactin receptor in rat NB2 lymphoma cells [3].
• We conclude that PRLR is distributed in normal rat liver in a typical pattern which is lost with increasing fibrosis [4].
• Androgen regulation of prolactin receptor content and androgen receptor distribution in A x C rat prostate cancer cells were comparable to those of the normal ventral prostate gland [5].

Psychiatry related information on Prlr

• Induction of brain prolactin receptor long-form mRNA expression and maternal behavior in pup-contacted male rats: promotion by prolactin administration and suppression by female contact [6].

High impact information on Prlr

• Evidence is accumulating that the secretory pattern of GH in the rat also affects various sexually differentiated hepatic characteristics such as steroid metabolism and prolactin receptor concentration [7].
• A prolactin receptor, present in adult female rat liver, can be induced in males by estrogen [8].
• Transient cotransfections in HepG2 cells revealed that PRL inducibility (2.5-3-fold) required coexpression of the long form of the PRL receptor (PRLRL) and Stat5 [9].
• For control NMU-induced rat mammary tumors, total PRL receptor levels were 6.35 +/- 1.40 fmol/mg protein, 7.20 +/- 2.40 fmol/mg protein for NMU-induced rat mammary tumors treated with o-PRL, and 6.81 +/- 2.34 fmol/mg protein for NMU-induced rat mammary tumors treated with CB-154 [10].
• Two lambda gt11 clones containing fragments of cDNA encoding the prolactin receptor from rabbit mammary gland were isolated using a rat liver prolactin receptor cDNA probe [11].

Chemical compound and disease context of Prlr

• The PRL-R in the arcuate nucleus was significantly increased in bromocriptine-treated rats and decreased in haloperidol-treated rats, suggesting that the PRL-R in this nucleus is regulated by mechanisms related to both the stimulus of suckling itself and suckling-induced hyperprolactinemia [12].

Biological context of Prlr

• However, the cDNA sequence is missing 594 base pairs in the cytoplasmic domain compared with the long form of the PRL-R [13].
• A cDNA was isolated from an Nb2-Sp cDNA library, which contains 1446 base pairs identical to the nucleotide sequence of the long form of the rat PRL-R [13].
• The identification of a modified long form of PRL-R in the Nb2 cell line should help localize domains of the PRL-R involved in signal transduction and further the investigation of prolactin's role in immune cell proliferation [13].
• The aim of the present study was to determine the time-course of changes in PRL-R mRNA levels during pregnancy and/or lactation, and to determine relative levels of the two forms (short and/or long form) of receptor mRNA in specific brain regions [14].
• These results indicate that PRL-R mRNA expression is almost consistent with PRL binding sites except for elongated spermatids and spermatozoa, and suggest that PRL may have direct effects on spermatogenic cells [15].

Anatomical context of Prlr

• These studies indicate that both cell lines express a novel form of PRL-R [13].
• In addition, immunoblot analysis of these microsomes using 125I-labeled monoclonal antibody (U6) to the PRL-R demonstrates a Mr of approximately 82,000 for the long form and approximately 62,000 for the Nb2 form of PRL-R [13].
• This leads to an elevated expression of the long form of PRLR (PRLR-L) first in the hypothalamus and the choroid plexus [1].
• Using primers that flanked the coding region for the extracellular binding domain we detected PRL-R mRNA in the anterior and medial basal hypothalamus, anterior and posterior pituitary gland, as well as in the liver, but not in the cerebral cortex or skeletal muscle [16].
• Detection of prolactin receptor (PRL-R) mRNA in the rat hypothalamus and pituitary gland [16].

Associations of Prlr with chemical compounds

• Distribution of prolactin receptor immunoreactivity in the brain of estrogen-treated, ovariectomized rats [17].
• Steroid-induced alterations in mRNA expression of the long form of the prolactin receptor in the medial preoptic area of female rats: Effects of exposure to a pregnancy-like regimen of progesterone and estradiol [18].
• Finally, glucose-induced insulin secretion was reduced in islets from pregnant but not from control rats treated with the PRLR antisense oligonucleotide [19].
• Cross-linking with ethylene glyco bis[succinimidyl-succinate] (mol. length of 16.1 A) generated a high mol. wt., [32P]-ADP-ribosylated band of 140-160 kD which also showed immunoreactivity with antiserum to the PRL receptor [3].
• Expression of mRNA for prolactin receptor (long form) in dopamine and pro-opiomelanocortin neurones in the arcuate nucleus of non-pregnant and lactating rats [20].

Physical interactions of Prlr

• Interaction of prolactin (PRL) binding sites with PRL receptor antibodies in rat liver cells in suspension culture: effect of inhibitors of cellular functions [21].
• Our results indicate that PRAP preferentially binds to the short form of the PRL receptor [22].
• The binding of [125I]human GH to the lactogen receptor as well as the binding of [125I]IL-2 to the IL-2 receptor were decreased in a dose-dependent manner by GTP, GDP, and the analog guanosine 5'-O-(3-thiotriphosphate) [23].

Regulatory relationships of Prlr

• A prolactin-dependent immune cell line (Nb2) expresses a mutant form of prolactin receptor [13].
• On the contrary, few ARH NPY neurons expressed PRL-R [24].
• Involvement of PI3'-K, mitogen-activated protein kinase and protein kinase B in the up-regulation of the expression of nNOSalpha and nNOSbeta splicing variants induced by PRL-receptor activation in GH3 cells [25].
• PRL receptor activation induced relaxin mRNA expression in a concentration- and time-dependent manner [26].
• We used nuclear translocation of STAT5 as a marker of prolactin receptor induced signaling and expression of Fos related antigens (FRAs) as an indicator of neuronal activation [27].

Other interactions of Prlr

• Polymerase chain reaction amplification of genomic DNA prepared from PRL-dependent and -independent cell lines suggests that this form of PRL-R results from a deletion in the PRL-R gene [13].
• Here we tested brain PRL-receptor (PRL-R)-mediated effects on anxiety, maternal behaviour, HPA axis and oxytocin stress responses in lactating rats [2].
• In contrast, A917 anti PRL-R also internalised in endosomes and in microvesicular bodies, was carried out to the Golgi apparatus and to the lumen of the acini after 5 min of incubation at 37 degrees C. These results suggest that an intracellular sorting occurs in the presence of the hormone or the different antibodies [28].
• Together these observations suggest that PRLR stimulation of pim-1 transcription occurs independently of a requirement for signaling through a Jak2/Stat mechanism [29].
• To determine whether PRAP associates with either the long or the short form of the PRL receptor, fusion proteins with glutathione S-transferase containing the cytoplasmic domain of the long or short form of the PRL receptor were produced, purified, and incubated with luteal proteins [22].

Analytical, diagnostic and therapeutic context of Prlr

• We also show that when measured after 7 h of RSW, microinjection of the PRLR antisense oligonucleotide into these areas down-regulates RSW-enhanced expression of PRLR-L protein in the PVN and increases the plasma PRL level, but does not affect plasma levels of another hormone, GH [1].
• By using monoclonal antibodies raised against purified rat liver PRL-R, the distribution of PRL-R was investigated by immunohistochemistry in brains of the estrogen-treated ovariectomized (OVX+E) rat and the adult male rat [17].
• RT-PCR analysis revealed the short and long form of PRL-R mRNA in both spleen and thymus at every age tested [30].
• Three approaches were taken to measure PRL-R expression: (i) polymerase chain reaction (RT-PCR); (ii) antibody to PRL-R and Western blotting; (iii) antibody to PRL-R and flow cytometry [30].
• In order to confirm the presence of PRL receptors on specific cell types of the anterior pituitary, immunocytology on ultrathin frozen sections was carried out using monoclonal antibodies specific to the rat PRL receptor [31].

References