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Molecular Reproduction and Development Sep 1997We have examined the developmental pattern of prolactin receptor expression in the mouse by reverse transcription-polymerase chain reaction, in situ hybridization, and...
We have examined the developmental pattern of prolactin receptor expression in the mouse by reverse transcription-polymerase chain reaction, in situ hybridization, and radioligand binding and have found two unexpected aspects of temporal regulation. First, high levels of prolactin receptor mRNA were detected in mouse embryos at day 8 and day 18, but levels decreased between these days to a minimum at approximately day 14. In contrast, placental prolactin receptor mRNA levels remained constant throughout this gestational period. Second, on embryonic day 16 the mRNA encoding the long form of the prolactin receptor is more abundant in the fetal liver than any of the short receptor form mRNAs, but by day 18 a switch occurs and the mRNA encoding one of the short receptor forms becomes the predominant receptor mRNA in that tissue. Expression of the receptor mRNA and protein is widespread throughout the fetus, with especially high levels in developing bone and cartilagenous structures, the thymus and pituitary, the tongue and skeletal muscle, and certain regions of the brain. The pattern of expression of prolactin receptor in the fetal mouse suggests an important role for the placental lactogens, the major ligands for fetal prolactin receptors, in fetal growth and development.
Topics: Animals; Embryo, Mammalian; Embryonic and Fetal Development; Gene Expression Regulation, Developmental; Mice; RNA, Messenger; Receptors, Prolactin; Time Factors
PubMed: 9266760
DOI: 10.1002/(SICI)1098-2795(199709)48:1<45::AID-MRD6>3.0.CO;2-P -
The New England Journal of Medicine Mar 2014
Topics: Female; Germ-Line Mutation; Humans; Hyperprolactinemia; Male; Receptors, Prolactin
PubMed: 24597880
DOI: 10.1056/NEJMc1315848 -
The New England Journal of Medicine Mar 2014
Topics: Female; Germ-Line Mutation; Humans; Hyperprolactinemia; Male; Receptors, Prolactin
PubMed: 24597877
DOI: 10.1056/NEJMc1315848 -
Recent Progress in Hormone Research 1993
Review
Topics: Amino Acid Sequence; Animals; Binding Sites; Gene Expression; Growth Hormone; Humans; Molecular Sequence Data; Prolactin; Receptors, Prolactin; Receptors, Somatotropin; Signal Transduction
PubMed: 8441846
DOI: 10.1016/b978-0-12-571148-7.50009-9 -
Trends in Endocrinology and Metabolism:... Nov 2010Breast and prostate cancers are hormone-sensitive malignancies that afflict millions of women and men. Although prolactin (PRL) is known as a survival factor that... (Review)
Review
Breast and prostate cancers are hormone-sensitive malignancies that afflict millions of women and men. Although prolactin (PRL) is known as a survival factor that supports tumor growth and confers chemoresistance in both cancers, its precise role in these tumors has not been studied extensively. Growth hormone and placental lactogen also bind PRL receptor (PRLR) and mimic some of the actions of PRL. Blockade of the PRLR represents a novel treatment for patients with advanced breast or prostate cancer with limited therapeutic options. This review discusses different approaches for generating PRLR antagonists. Emphasis is placed on technological advances which enable high-throughput screening for small molecule inhibitors of PRLR signaling that could serve as oral medications.
Topics: Animals; Breast Neoplasms; Carcinoma; Female; High-Throughput Screening Assays; Hormone Antagonists; Humans; Male; Models, Biological; Models, Molecular; Molecular Targeted Therapy; Prostatic Neoplasms; Receptors, Prolactin; Therapies, Investigational
PubMed: 20846877
DOI: 10.1016/j.tem.2010.08.004 -
Journal of Neuroendocrinology Jul 2010The involvement of prolactin in human tumourogenesis has been long debated. The reason is that the evidence supporting the role of circulating prolactin in promoting... (Review)
Review
The involvement of prolactin in human tumourogenesis has been long debated. The reason is that the evidence supporting the role of circulating prolactin in promoting breast cancer was mainly obtained using rodent models, whereas most of the studies performed in human species in the 1980s have remained inconclusive. Things have now started to change because two alternative mechanisms of prolactin actions in tumour growth have emerged since the beginning of the 21st Century. The first involves locally-produced prolactin, which acts by an autocrine/paracrine mechanism. Genetically-modified mouse models have demonstrated the tumourigenic potential of local prolactin on the prostate and the mammary gland, and arguments are now emerging in humans also. The second mechanism involves genetic variants of the receptor. Although no genetic disorder has been reported for prolactin or its receptor, a variant of the prolactin receptor exhibiting constitutive activity has been recently identified in patients presenting with breast tumours, suggesting that sustained prolactin signalling may participate in breast tumourogenesis. Recent data regarding these two nonclassical mechanisms of prolactin action are discussed. Finally, we address the question of their inhibition in future cancer therapy, both in light of other findings that have revealed novel actions of prolactin in breast cancer cells, and with respect to the compounds currently available to target prolactin receptor signalling.
Topics: Animals; Autocrine Communication; Breast Neoplasms; Female; Genetic Variation; Humans; Prolactin; Receptors, Prolactin; Signal Transduction
PubMed: 20456598
DOI: 10.1111/j.1365-2826.2010.02011.x -
Acta Histochemica Jan 2021Prolactin receptor (PRLR), a type-1 cytokine receptor, is overexpressed in a number of cancer types. It has attracted much attention for putative pro-oncogenic roles,...
Prolactin receptor (PRLR), a type-1 cytokine receptor, is overexpressed in a number of cancer types. It has attracted much attention for putative pro-oncogenic roles, which however, remains controversial in some malignancies. In this study, we reported the localization of PRLR to the Hodgkin's and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL), a neoplasm of predominantly B cell origin. Immunohistochemistry performed on 5-μm thick FFPE sections revealed expression of PRLR in HRS cells. Cellular immunofluorescence experiments showed that the HL-derived cell lines, Hs445, KMH2 and L428 overexpressed PRLR. The PRLR immunofluorescent signal was depleted after treating the cell lines with 10 μM of siRNA for 48 h. We also tested whether PRLR is involved in the growth of HL, in vitro. One-way analysis of variance (ANOVA) on cell growth data obtain from WST-1 cell proliferation assay and trypan blue exclusion assay and hemocytometry showed that siRNA-depletion of PRLR expression resulted in decreased growth in all three cell lines. These results offered only a short insight into the involvement of PRLR in HL. As a result, further investigation is required to decipher the precise role(s) of PRLR in the pathogenesis of HL.
Topics: Cell Line, Tumor; Hodgkin Disease; Humans; Immunohistochemistry; Neoplasm Proteins; Receptors, Prolactin; Reed-Sternberg Cells
PubMed: 33259941
DOI: 10.1016/j.acthis.2020.151657 -
Frontiers in Neuroendocrinology Apr 2001The development of a mouse line deficient in the PRL receptor (PRLR) would be an ideal means to better understand the multiple functions of prolactin. We were worried... (Review)
Review
The development of a mouse line deficient in the PRL receptor (PRLR) would be an ideal means to better understand the multiple functions of prolactin. We were worried initially that removal of the PRLR from the mouse genome might be lethal and were surprised to find this not to be the case. We identified numerous deficiencies in PRLR knockout (KO) animals. Female homozygous mice are completely infertile and lack normal mammary development, while hemizygotes are unable to lactate following their first pregnancy. PRLR KO males and females have markedly elevated (30- to 100-fold) serum prolactin levels and in some instances pituitary hyperplasia is present. Maternal behavior is severely affected in both hemizygous and heterozygous animals. Bone formation is reduced in young animals and adults (males and females). Recently, we noticed that older KO animals show a slight reduction in body weight which appears to be due to reduced abdominal fat deposition.
Topics: Animals; Behavior, Animal; Blood Proteins; Bone Development; Female; Fertility; Immune System; Lactation; Mammary Glands, Animal; Maternal Behavior; Mice; Mice, Knockout; Phenotype; Receptors, Prolactin; Signal Transduction
PubMed: 11259135
DOI: 10.1006/frne.2001.0212 -
Sheng Li Ke Xue Jin Zhan [Progress in... Feb 2012Prolactin (PRL) is secreted by lactotrophs in the anterior pituitary and some extra-pituitary tissues such as breast, lacrimal gland, uterus, thymus and spleen, etc.... (Review)
Review
Prolactin (PRL) is secreted by lactotrophs in the anterior pituitary and some extra-pituitary tissues such as breast, lacrimal gland, uterus, thymus and spleen, etc. Since PRL is closely related to growth hormone (GH) and placental lactogens (PL), it has been broadly accepted that PRL, GH and PL are resulted from the duplication of an ancestral gene. PRL regulates hundreds of biological functions by endocrine, paracrine and autocrine manners. Prolactin initiates its effects by binding to its receptor (PRLR). PRLR belongs to the class I cytokine receptor superfamily. Up to now, three membrane--PRLRs have been clarified. They are long form (LF), intermediate form (IF) and short form (SF) including SFla and SFlb. All PRLRs are derived from a primary transcript of common gene through alternative splicing mechanism. Although the extracellular domain (ECD) and the transmembrane domain (TD) of LF, IF and SF are equal, different isoforms of PRLR exert different function through different intracellular domain. It has been well documented that abnormity of PRLR is closely related to the pathogenesis, progression and prognosis of cancers including breast cancer. Several PRLR antagonists have been well designed and evidenced to have the potential to be important therapeutics.
Topics: Animals; Breast Neoplasms; Humans; Receptors, Prolactin
PubMed: 22582593
DOI: No ID Found -
General and Comparative Endocrinology Feb 2019Chicken early (EF) and late feathering (LF) are sex-linked phenotypes conferred by wild-type k and dominant K alleles on chromosome Z, respectively. Besides prolactin...
Chicken early (EF) and late feathering (LF) are sex-linked phenotypes conferred by wild-type k and dominant K alleles on chromosome Z, respectively. Besides prolactin (PRL) receptor (PRLR) and sperm flagellar 2 (SPEF2) genes, the K allele contains a fusion gene in which partially duplicated PRLR (dPRLR) and SPEF2 (dSPEF2) genes are linked in a tail-to-tail manner. The causative dPRLR gene encodes a C-terminal truncated receptor. LF chickens have short or no primaries at hatching; however, their feather growth rate is higher than that of EF chickens. This study aimed to elucidate the molecular basis of the K allele's biphasic effect on feather development. By 3'RACE and RT-PCR analyses, we demonstrated that dSPEF2 gene transcription occurred beyond all coding exons of the dPRLR gene on the opposite strand and that dPRLR mRNA was less abundant than PRLR mRNA. In addition, a 5'UTR splice variant (SPV) of PRL receptor mRNAs was increased in LF chickens. In vitro expression analysis of 5'UTR linked to the luciferase reporter gene revealed higher translation efficiency of SPV. RT-qPCR showed that the dPRLR mRNA level was higher in embryos; conversely, SPV was higher in hatched chickens, as was dSPEF2 mRNA. These findings suggest that the K allele inhibits feather development at the fetal stage by expressing dPRLR to attenuate PRLR function and promotes feather growth after hatching by increasing PRLR through dSPEF2 mRNA expression. Increased SPV may cause greater feather growth than that in EF chickens by increasing the availability of PRLR homodimers and enhancing PRL signaling.
Topics: Animals; Chickens; Feathers; Female; Receptors, Prolactin
PubMed: 30594591
DOI: 10.1016/j.ygcen.2018.12.011