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Details for receptor: PRLR

EndoNet ID: ENR00263

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Synonyms

  • PRLR
  • prolactin receptor

General information

  • Expression of PRL-R was identified in human testis and vas deferens by RT–PCR, and further localized by immunohistochemistry to the Leydig cells and differentiating germ cells of the testis. [1]
  • Positive staining for PRL-R was also clearly evident in the epithelium of vas deferens, epididymis, prostate and seminal vesicles. [1]
  • [2]
  • Prolactin receptor gene expression and immunolocalization of the prolactin receptor in human luteinized granulosa cells. [3]

Links to other resources

UniProt P16471
Ensembl ENST00000397391

Subunit information

Sequence
QLPPGKPEI FKCRSPNKE TFTCWWRPG 
TDGGLPTNY SLTYHREGE TLMHECPDY 
ITGGPNSCH FGKQYTSMW RTYIMMVNA 
TNQMGSSFS DELYVDVTY IVQPDPPLE 
LAVEVKQPE DRKPYLWIK WSPPTLIDL 
KTGWFTLLY EIRLKPEKA AEWEIHFAG 
QQTEFKILS LHPGQKYLV QVRCKPDHG 
YWSAWSPAT FIQIPSDFT MNDTTVWIS 
VAVLSAVIC LIIVWAVAL KGYSMVTCI 
FPPVPGPKI KGFDAHLLE KGKSEELLS 
ALGCQDFPP TSDYEDLLV EYLEVDDSE 
DQHLMSVHS KEHPSQGMK PTYLDPDTD 
SGRGSCDSP SLLSEKCEE PQANPSTFY 
DPEVIEKPE NPETTHTWD PQCISMEGK 
IPYFHAGGS KCSTWPLPQ PSQHNPRSS 
YHNITDVCE LAVGPAGAP ATLLNEAGK 
DALKSSQTI KSREEGKAT QQREVESFH 
SETDQDTPW LLPQEKTPF GSAKPLDYV 
EIHKVNKDG ALSLLPKQR ENSGKPKKP 
GTPENNKEY AKVSGVMDN NILVLVPDP 
HAKNVACFE ESAKEAPPS LEQNQAEKA 
LANFTATSS KCRLQLGGL DYLDPACFT 
HSFH
UniProt P16471-1

Binding hormones

  • GH
    (trough: blood
    )
  • PRL
  • CSH1

Anatomical structures with this receptor

  • adrenal_cortex

    Induced phenotypes

    • positive regulation of steroid biosynthetic process
      • A direct action of PRL on adrenal steroidogenesis has been reported. Specifically, PRL is able to increase adrenal androgens, dihydroepiandrosterone and dihydroepianstrosterone sulfate as well as cortisol and aldosterone. [4]
  • pancreatic_islets

    Induced phenotypes

    • regulation of glucose metabolic process
      • n adult rat islets, rPRL was also more effective than rGH in increasing insulin secretion [5]
  • corpus_luteum

  • mammary_gland

    Induced phenotypes

    • synthesis of milk proteins
      • Prolactin is the hormone primarily responsible for the synthesis of milk proteins. [6]
    • synthesis of lipids
      • Prolactin is the hormone primarily responsible for the synthesis of lipids. [7]
    • synthesis of lactose
      • Prolactin is the hormone primarily responsible for the synthesis of lactose. [8]
    • mammary gland development
      • The terminal stage of mammary gland development, lobuloalveolar growth, is directly regulated by prolactin. [4]
  • testis

    Induced phenotypes

    • maturation of germ cells
      • Prolactin induces maturation of germ cells. Prolonged suppression of prolactin (PRL) in immature male rats inhibits the spermatocyte-spermatid conversion process, alters leydig cell morphology, decreases accessory sex organ weight and increases serum LH levels without a significant alteration in serum FSH concentration. Amelioration of these effects by exogenous PRL strongly indicates that in the absence of PRL excess titers of endogenous LH fail to exert an influence on the spermatogenic activity of maturing testes. [9]
    • impotence
      • In humans, hyperprolactinemia has been shown to be associated with impotence. [10]
  • prostate

    Induced phenotypes

    • proliferation of epithelial cells
      • Prolactin induces the proliferation of human benign prostate hypertrophy epithelial cells. [11]
    • prostate gland growth
      • Prolactin has effects on accessory sex organs, it increases the weight of the prostate and seminal vesicle, in conjunction with androgens. [12]
    • regulation of androgen receptor signaling pathway
      • The effects of PRL on prostate include increased levels of androgen receptor. [13]
      • PRL and GH are involved in regulating AR synthesis, at least partially by direct action on the organ. [13]
    • positive regulation of secretion
      • The effects of PRL on prostate include increased epithelial secretory function. [14]
    • energy reserve metabolic process
      • The effects of Prolactin on prostate include augmented energy metabolism and an enhancement of citric acid production. [15]
    • positive regulation of insulin-like growth factor receptor signaling pathway
      • Prolactin has been reported to stimulate the level of IGF-I and IGF-I receptor in the prostate. [13]
      • PRL and GH are involved in regulating AR synthesis, at least partially by direct action on the organ. In this context IGF-I appears as a paracrine factor playing a role in epithelium/stroma interactions during prostatic development. [13]
    • positive regulation of lipid metabolic process
      • In the seminal vesicle, PRL increases lipid concentrations in the fluid, lipogenesis, and phosphomonoesterase and acid phosphatase activities. [4]
    • regulation of inflammatory response
      • The effects of PRL on prostate include involvement in estrogen-induced inflammation. [16]
      • Estradiol-induced inflammation in the rat lateral prostate is mediated at least in part by the release of PRL from the pituitary. [16]
  • granulosa_cell

    Influences

    • negative estrogen
      • In granulose cells. prolactin inhibits estrogen synthesis. [17]
  • arcuate_nucleus_of_hypothalamus

    Influences

    • positive GHRH
    • positive dopamine
  • fat_cell_of_brown_fat

    Influences

    • positive leptin
      • Prolactin combined with insulin significantly increases leptin expression and release from differentiated brown adipocytes, indicating that prolactin potentiates the stimulatory effect of insulin as revealed by the recruitment of insulin receptor substrates and the activation of phosphatidylinositol 3-kinase. [18]
      • Prolactin is not directly involved in transcription rate, but more likely in the secretion or release process of leptin in vivo. [18]
  • central_nerve_system_element

    Induced phenotypes

    • experimental allergic encephalomyelitis
      • Prolactin has been shown to be increases and to effect a number of autoimmune states, such as acute experimental allergic encephalomyelitis. [19]
      • Prolactin levels are elevated after immunization and before the onset of experimental allergic encephalomyelitis, bromocriptine inhibits both prolactin secretion and the severity of acute experimental allergic encephalomyelitis, and inhibition is also present when treatment is begun after sensitization, suggesting an effect of prolactin on the effector limb of the immune response during experimental allergic encephalomyelitis. [19]
    • Systemic lupus erythematosus
      • Prolactin has been shown to be increases and to effect a number of autoimmune states, such as systemic lupus erythematosus. [20]
  • brain

    Induced phenotypes

    • hyperphagia
      • Increased Food intake (hyperphagia) can be observed in mammals in response to prolactin. Elevated prolactin levels stimulate food intake in a dose-dependent manner. [21]
    • decrease in libido
      • Elevated circulating prolactin is also thought to be responsible libido. [22]
    • modulation of ATPase activity
      • Prolactin has specific effect on different ATPases, in different regions of the brain. PRL has been shown to effect energy metabolism by modulating ATPase activity in monkey brain: Na+-K+-dependent ATPase was stimulated while Mg2+ and Ca2+-dependent ATPases were reduced in neural as well as glial cells. [23]
    • regulation of sensory perception of pain
      • Prolactin has been shown to have analgesic effects that can be mimicked by a number of central nervous system neurotransmitters. [24]
    • alteration of sleep-wake-cycle
      • Elevated circulating prolactin is thought to be responsible for and alteration of the sleep-wake-cycle. [25]
    • increase in REM sleep
      • Elevated circulating prolactin is thought to be responsible for increased rapid eye movement sleep. [26]
    • adaptive stress response
      • One set of behavioral responses that are induced by prolactin are adaptive stress responses. PRL plays a protective role against stress-induced biological modifications in animals. [27]
    • modulation of carbohydrate metabolism
      • PRL affects carbohydrate metabolism in several vertebrate classes, including hyperglycemic/diabetogenic actions. PRL has a differential effect on the activities of enzymes involved in the Embden-Meyerhoff pathway and the hexose monophosphate shunt in neural and glial cells of male monkeys. [28]
    • induction of excessive grooming
      • PRL is considered to be responsible for inducing excessive grooming in rats. [29]
    • pseudopregnancy
      • In women, elevated levels of prolactin are associated with some phsychosomatic reactions, including a form of pseudopregnancy. [30]
  • hippocampus

  • renal_cortex

  • corpus_striatum

  • cochlea

  • corpus_callosum

  • hypothalamus

    Induced phenotypes

    • tuberoinfundibular hypothalamic development
      • Prolactin induces tuberoinfundibular hypothalamic dopamine development. [31]
    • organ maturation
      • In the hypothalamus, prolactin has been suggested to be important for maturation of the neonatal neuroendocrine system. [32]
  • astrocyte

    Induced phenotypes

    • regulation of cell proliferation
      • Prolactin induces the proliferation of astrocytes. [33]
  • glial_cell_of_central_nervous_system

  • retina

  • olfactory_bulb

  • cell_of_intermediate_pituitary

  • skin

    Induced phenotypes

    • stimulation of keratinocyte growth
      • PRL stimulates keratinocyte growth in mammals. [34]
    • positive regulation of steroid biosynthetic process
      • In the skin, Prolactin increases the expression of type IV 3beta-hydroxysteroid dehydrogenase. [35]
    • cystic fibrosis
      • Prolactin has been suggested to be involved in the etiology of cystic fibrosis. [36]
      • Cystic fibrosis may involve defective prolactin production leading to failure of regulation of Cl channels in affected epithelia. [36]
    • positive regulation of cell proliferation
      • Prolactin stimulates skin melanocyte growth in mammals. [37]
  • epidermis

  • hair_follicle

    Induced phenotypes

    • hair growth
  • sweat_glands

    Induced phenotypes

    • reduction of electrolyte excretion
      • Reduced Na+ and Cl- in sweat [38]
    • cystic fibrosis
      • Cystic fibrosis may involve defective PRL production leading to failure of regulation of Cl channels in affected epithelia. [36]
  • bone

  • chondrocyte

  • cartilage

  • osteoblast

  • lung

    Induced phenotypes

    • organ maturation
      • PRL induces maturation of the lung. [39]
    • surfactant production
      • Prolactin induces surfactant production. [40]
    • stimulation of phospholipid synthesis
      • PRL has marked effects on lipid metabolism. In mammals, PRL stimulates phospholipid synthesis in the fetal lung. [39]
  • heart

  • cardiac_muscle

  • skeleton_muscle

  • hepatocyte

    Induced phenotypes

    • increase in glycogen phosphorylase-a activation
      • PRL at physiological concentrations produced a 4-fold increase in glycogen phosphorylase-a activation in isolated hepatocytes. [41]
    • positive regulation of cell proliferation
      • PRL plays an important role in the turnover of hepatocytes. There was a striking increase in the number of mitotic figures in livers of transgenic mice expressing hGH, which binds equally well to PRL and GH receptors. [42]
  • liver

    Induced phenotypes

    • increase in bile secretion
      • Prolactin has been shown to increase bile secretion. [43]
    • stimulation of lipoprotein lipase activity
      • Prolactin has marked effects on lipid metabolism. PRL stimulates lipoprotein lipase activity in the liver. [44]
    • Factor XII activation
      • In terms of more specific protective effects, PRL induces the production of coagulation factor XII by the liver. [45]
  • Kupffer_cell_stellate_cell_of_liver

    Induced phenotypes

    • reduction of cytokine gene expression
      • Haemorrhage markedly increases the level of mRNA for IL-1 beta, IL-6, TGF-beta and TNF-beta in Kupffer cells. In vivo PRL treatment significantly decreases the cytokine gene expression in Kupffer cells following haemorrhage. Thus, PRL may be useful in blunting the systemic inflammatory response associated with cell and organ depression following shock. [46]
    • positive regulation of cytokine biosynthetic process
      • In synergy with IFN-gamma, PRL decreases monoblastic growth and increases cytokine gene expression in Kupffer cells after hemorrhage. [46]
  • submandibular_gland

  • pancreas

    Influences

    • positive insulin
      • PRL is known to have direct effects on pancreatic function, increasing insulin secretion and decreasing glucose threshold for insulin secretion. [47]

    Induced phenotypes

    • regulation of glucose metabolic process
      • PRL is known to have direct effects on pancreatic function, increasing insulin secretion, decreasing glucose threshold for insulin secretion, and increasing glucokinase and glucose transporter 2 . [48]
    • positive regulation of cell proliferation
      • PRL induces proliferation of beta-cells of the pancreas. [49]
  • digestive_system

    Induced phenotypes

    • increase in size of intestinal mucosa
      • PRL induces an increase in the size of the intestinal mucosa. [50]
    • multicellular organismal water homeostasis
      • increased water and salt absorption in intestine [51]
      • Duodenum: Na+ and Ca2+ [52]
      • Jejunum: Na+, K+, Ca2+ [53]
      • Ileum: Na+, Cl-, K+, Ca2+ [54]
      • Colon: Na+ and Cl- [55]
  • oesophagus

  • stomach

  • duodenum

  • jejunum

  • ileum

  • colon

    Induced phenotypes

    • colorectal cancer
      • Prolactin is thought to increase colorectal tumor agressivity. [56]
  • kidney

    Induced phenotypes

    • multicellular organismal water homeostasis
      • PRL is clearly involved in water and electrolyte balance in almost all classes of vertebrates, PRLRs are present in kidney, as well as other tissues involved in salt balance. [4]
    • reduction of electrolyte excretion
      • PRL plays a major role in regulating water and electrolyte balance through the kidney by stimulation of Na+-K+-ATPase and reduction of Na+ and K+ excretion. [57]
  • lymphoid_tissue

  • spleen

  • thymus

  • thymic_epithelial_cell

    Influences

    • positive Thymulin
      • Prolactin augments the production of a thymic hormone, thymulin. [58]
      • PRL can stimulate thymulin synthesis and secretion both in vitro and in vivo. [58]
    • TEC possess PRL receptors. [59]
  • B-lymphocyte

  • lymphocyte

    Induced phenotypes

    • positive regulation of immunoglobulin production
      • In lymphocytes, PRL is known to increase antibody formation, including IgG and IgM antibodies. [60]
    • positive regulation of lymphocyte proliferation
      • In lymphocytes, PRL is known to induce cellular proliferation. [61]
    • interleukin-2 receptor complex
      • Prolactin has to been reported to increase receptor levels for interleukin-2. [62]
    • erythropoietin receptor activity
      • Prolactin has been reported to increase receptor levels for erythropoietin. [63]
    • prolactin receptor activity
      • Prolactin has been reported to increase receptor levels for prolactin. [64]
    • negative regulation of lymphocyte apoptosis
      • In addition to stimulating proliferation, PRL has been shown to inhibit apoptosis of lymphocytes. [65]
    • activation of malignant B cells
      • Prolactin is thought to activate malignant B lymphocytes. [66]
      • Prolactin has a role in the growth of some cancers of lymphoid origin in rats. [67]
    • regulation of immune system process
      • Administration of PRL is associated with increased graft rejection. [68]
  • T-lymphocyte

    Induced phenotypes

    • regulation of immune system process
      • Administration of PRL is also associated with an increase in T cell engraftment. [69]
  • macrophage

    Induced phenotypes

    • macrophage activation during immune response
      • It has been shown that macrophage activation and superoxide anion production responsible for killing pathogenic organisms are effects mediated by the PRLR. [70]
      • Activation of macrophages was originally thought to be an action of GH. However, it has been shown that macrophage activation is an effect mediated by the prolactin receptor. [71]
  • ovary

    Influences

    • positive progesterone
      • The luteotropic action of prolactin involves stimulation of progesterone production by luteal cells. [72]

    Induced phenotypes

    • maturation of germ cells
      • Prolcatin induces maturation of germ cells. Prolactin appears to be an important constituent in the process of oocyte maturation, promoting preimplantation embryonic development. [73]
    • amenorrhea
      • In humans, hyperporlactinemia has been shown to be associated with amenorrhea. [10]
  • theca_cell

  • corpus_luteum

  • uterus

    Induced phenotypes

    • increase in progesterone receptor level
      • In the uterus, prolactin is able to increase the level of progesterone receptors, and thus all actions associated with this steroid hormone are enhanced. [74]
    • increase in estrogen receptor level
      • In the uterus, prolactin has a stimulatory effect on estrogen receptor levels. [75]
    • embryo implantation
      • Prolactin promotes blastocyst implantation. [76]
    • uterine leiomyomas
      • Benign fibromuscular myometrial tumors (leiomyomas) have been shown to produce more PRL than control myometrium; thus, locally produced PRL may exert a mitogenic action on the growth of these tumors. [77]
  • placenta

    Induced phenotypes

    • multicellular organismal water homeostasis
      • PRL induces a redution in fluid volume in the amnion. [78]
  • Leydig_cell_of_testis

    Induced phenotypes

    • stimulation of testicular function
      • Prolactin increases the LH receptor number in Leydig cells. [79]
      • In general, prolactin stimulates testicular functions in most mammals. In Leydig cells, prolactin is involved in the maintenance of cellular morphology. [80]
  • Sertoli_cell

    Induced phenotypes

    • increase in FSH receptor number
      • In Sertoli cells, prolactin has been shown to increase FSH receptor numbers. [81]
  • epididymis

    Induced phenotypes

    • positive regulation of lipid metabolic process
      • Prolactin has metabolic effects on sex accessory organs, in the epididymis, lipid levels are augmented.
    • energy reserve metabolic process
      • Prolactin has metabolic effects on sex accessory organs, in the epididymis, sialic acid levels are augmented. [82]
      • Prolactin has metabolic effects on sex accessory organs, in the epididymis, energy metabolism is increased. [83]
  • smooth_muscle_cell

    Induced phenotypes

    • positive regulation of smooth muscle proliferation
      • Prolactin induces proliferation of vascular smooth muscle cells through a protein kinase C-dependent mechanism. [84]
  • preadipocyte

    Induced phenotypes

    • differentiation of preadipocytes
      • Prolactin induces differentiation of preadipocytes. Prolactin and its receptor play a role in differentiation and/or metabolism of pre-adipocytes and adipocytes. [85]
  • breast

    Induced phenotypes

    • galactorrhea
      • In humans, hyperprolactinemia has been shown to be associated with galactorrhea. [10]
    • breast cancer
      • Prolactin is thought to induce the proliferation of several lines of human breast cancer. [4]
      • Not only 17 beta-estradiol but also prolactin is of major importance leading to enhanced proliferation of MXT mammary neoplastic cells. [86]
      • The human breast cancer cell line MCF-7 is highly responsive to growth stimulation by homologous lactogenic hormones. This then affords a possible role of prolactin in growth and maintenance of human breast cancer. [87]
      • The peptide hormone prolactin regulates proliferation of normal and malignant mammary cells. [88]
  • chorion

    Induced phenotypes

    • polyhydramnios
      • An excessive volume of amniotic fluid, known as polyhydramnios, is associated with decreased levels of amniotic fluid PRL or PRLR levels in the chorion laeve. [89]
      • This effect may be related to the osmoregulatory role of PRL during fetal life and to the inhibitory effect on amniotic fluid volume observed in monkeys. [78]
  • immune_system

    Induced phenotypes

    • rheumatoid arthritis
      • Prolactin has been shown to be increases and to effect a number of autoimmune states, such as rheumatoid arthritis. [90]
      • Children with antinuclear antibodies seropositive juvenile rheumatoid arthritis have elevated serum levels of the immunostimulatory hormone prolactin. [90]
    • graft-versus-host disease
      • Prolactin is released by mononuclear leucocytes and is involved in lymphocyte activation. It plays a hitherto unrecognized role in the pathogenesis of GVHD in humans. [91]
      • Prolactin has been shown to be increased in and to effect a number of autoimmune states, such as graft-versus-host disease. [91]
    • adjuvant arthritis
      • Prolactin has been shown to be increases and to effect a number of autoimmune states, such as adjuvant arthritis. [92]
Reference