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Endocrine Reviews Aug 2012Prolactin and the prolactin receptors are members of a family of hormone/receptor pairs which include GH, erythropoietin, and other ligand/receptor pairs. The mechanisms... (Review)
Review
Prolactin and the prolactin receptors are members of a family of hormone/receptor pairs which include GH, erythropoietin, and other ligand/receptor pairs. The mechanisms of these ligand/receptor pairs have broad similarities, including general structures, ligand/receptor stoichiometries, and activation of several common signaling pathways. But significant variations in the structural and mechanistic details are present among these hormones and their type 1 receptors. The prolactin receptor is particularly interesting because it can be activated by three sequence-diverse human hormones: prolactin, GH, and placental lactogen. This system offers a unique opportunity to compare the detailed molecular mechanisms of these related hormone/receptor pairs. This review critically evaluates selected literature that informs these mechanisms, compares the mechanisms of the three lactogenic hormones, compares the mechanism with those of other class 1 ligand/receptor pairs, and identifies information that will be required to resolve mechanistic ambiguities. The literature describes distinct mechanistic differences between the three lactogenic hormones and their interaction with the prolactin receptor and describes more significant differences between the mechanisms by which other related ligands interact with and activate their receptors.
Topics: Amino Acid Sequence; Animals; Erythropoietin; Growth Hormone; Humans; Molecular Structure; Prolactin; Protein Isoforms; Receptors, Prolactin; Thermodynamics
PubMed: 22577091
DOI: 10.1210/er.2011-1040 -
Channels (Austin, Tex.) 2014Prolactin (PRL) activates PRL receptor isoforms to exert regulation of specific neuronal circuitries, and to control numerous physiological and clinically-relevant... (Review)
Review
Prolactin (PRL) activates PRL receptor isoforms to exert regulation of specific neuronal circuitries, and to control numerous physiological and clinically-relevant functions including; maternal behavior, energy balance and food intake, stress and trauma responses, anxiety, neurogenesis, migraine and pain. PRL controls these critical functions by regulating receptor potential thresholds, neuronal excitability and/or neurotransmission efficiency. PRL also influences neuronal functions via activation of certain neurons, resulting in Ca(2+) influx and/or electrical firing with subsequent release of neurotransmitters. Although PRL was identified almost a century ago, very little specific information is known about how PRL regulates neuronal functions. Nevertheless, important initial steps have recently been made including the identification of PRL-induced transient signaling pathways in neurons and the modulation of neuronal transient receptor potential (TRP) and Ca(2+) -dependent K(+) channels by PRL. In this review, we summarize current knowledge and recent progress in understanding the regulation of neuronal excitability and channels by PRL.
Topics: Animals; Humans; Ion Channels; Neurons; Prolactin; Receptors, Prolactin; Signal Transduction
PubMed: 24758841
DOI: 10.4161/chan.28946 -
Folia Biologica 2014Prolactin (PRL), secreted from the anterior pituitary, plays extensive roles in osmoregulation, corpus luteum formation, mammogenesis, lactogenesis, lactopoiesis, and... (Review)
Review
Prolactin (PRL), secreted from the anterior pituitary, plays extensive roles in osmoregulation, corpus luteum formation, mammogenesis, lactogenesis, lactopoiesis, and production of crop milk. In birds, prolactin (PRL) is generally accepted as crucial to the onset and maintenance of broodiness. All the actions of prolactin (PRL) hormone are mediated by its receptor (PRLR), which plays an important role in the PRL signal transduction cascade. It has been well established that the PRL gene is closely associated to the onset and maintenance of broody behavior, and could be a genetic marker in breeding against broodiness in chickens. Meanwhile, the prolactin receptor (PRLR) gene is regarded as a candidate genetic marker for reproductive traits. PRLR is also an important regulator gene for cell growth and differentiation. The identified polymorphism of this gene is mainly viewed in terms of egg production traits. Due to different biological activities attributed to PRL and PRLR, they can be used as major candidate genes in molecular animal breeding programs. Characterization of PRL and PRLR genes helps to elucidate their roles in birds and provides insights into the regulatory mechanisms of PRL and PRLR expression conserved in birds and mammals.
Topics: Animals; Gene Expression Regulation; Poultry; Prolactin; Receptors, Prolactin
PubMed: 24745142
DOI: 10.3409/fb62_1.1 -
Reviews of Reproduction Jan 1997Prolactin mediates its effect on target cells through an interaction with membrane-anchored receptors. In the last decade, several subtypes of the receptor have been... (Review)
Review
Prolactin mediates its effect on target cells through an interaction with membrane-anchored receptors. In the last decade, several subtypes of the receptor have been isolated from different species. This has generated a great deal of interest in the roles of the receptor subtypes and the possible divergent signalling pathways in mediating the pleiotropic effects of prolactin on target tissues. Our current knowledge of the signalling pathway of prolactin is derived mainly from the interaction of the hormone with one of its receptor subtypes (the long form) isolated from rats. In vitro expression studies have led to the identification of the regions within the long form prolactin receptor that are essential for the association of the tyrosine kinase Jak-2, and the phosphorylation events leading to activation of the prolactin responsive beta-casein promoter. To date, a specific target gene that may be activated after interaction of prolactin with the short form of the receptor has not been identified. However, the different receptor subtypes are present in the same cell type in vivo and their expression is hormone regulated, possibly through multiple promoters that control transcription of the prolactin receptor gene. Comparative studies suggest that the signalling pathways and the relevance of different receptor subtypes on prolactin function may vary between species.
Topics: Animals; Carrier Proteins; DNA, Complementary; Female; Gene Expression Regulation; Humans; Male; Mice; Ovary; Pregnancy; Prolactin; Rabbits; Rats; Receptors, Prolactin; Signal Transduction; Species Specificity; Testis
PubMed: 9414461
DOI: 10.1530/ror.0.0020014 -
General and Comparative Endocrinology Jan 2022During breeding, multiple circulating hormones, including prolactin, facilitate reproductive transitions in species that exhibit parental care. Prolactin underlies...
During breeding, multiple circulating hormones, including prolactin, facilitate reproductive transitions in species that exhibit parental care. Prolactin underlies parental behaviors and related physiological changes across many vertebrates, including birds and mammals. While circulating prolactin levels often fluctuate across breeding, less is known about how relevant target tissues vary in their prolactin responsiveness via prolactin receptor (PRLR) expression. Recent studies have also investigated prolactin (PRL) gene expression outside of the pituitary (i.e., extra-pituitary PRL), but how PRL gene expression varies during parental care in non-pituitary tissue (e.g., hypothalamus, gonads) remains largely unknown. Further, it is unclear if and how tissue-specific PRL and PRLR vary between the sexes during biparental care. To address this, we measured PRL and PRLR gene expression in tissues relevant to parental care, the endocrine reproductive hypothalamic-pituitary- gonadal (HPG) axis and the crop (a tissue with a similar function as the mammalian mammary gland), across various reproductive stages in both sexes of a biparental bird, the rock dove (Columba livia). We also assessed how these genes responded to changes in offspring presence by adding chicks mid-incubation, simulating an early hatch when prolactin levels were still moderately low. We found that pituitary PRL expression showed similar increases as plasma prolactin levels, and detected extra-pituitary PRL in the hypothalamus, gonads and crop. Hypothalamic and gonadal PRLR expression also changed as birds began incubation. Crop PRLR expression correlated with plasma prolactin, peaking when chicks hatched. In response to replacing eggs with a novel chick mid-incubation, hypothalamic and gonadal PRL and PRLR gene expression differed significantly compared to mid-incubation controls, even when plasma prolactin levels did not differ. We also found sex differences in PRL and PRLR that suggest gene expression may allow males to compensate for lower levels in prolactin by upregulating PRLR in all tissues. Overall, this study advances our understanding of how tissue-specific changes in responsiveness to parental hormones may differ across key reproductive transitions, in response to offspring cues, and between the sexes.
Topics: Animals; Columbidae; Crop, Avian; Female; Gene Expression; Hypothalamo-Hypophyseal System; Male; Pituitary Gland; Pituitary-Adrenal System; Prolactin; Receptors, Prolactin
PubMed: 34756919
DOI: 10.1016/j.ygcen.2021.113940 -
Zygote (Cambridge, England) Feb 2022In this study, differential mRNA expression patterns of prolactin receptor (PRLR) in the hypothalamus and gonads, and the correlation with follicle stimulating hormone...
In this study, differential mRNA expression patterns of prolactin receptor (PRLR) in the hypothalamus and gonads, and the correlation with follicle stimulating hormone (FSH) and luteinizing hormone (LH) in striped hamster serum from spring, summer, autumn and winter were analyzed. Mature female and male striped hamsters in oestrus were used. Expression levels of PRLR in the hypothalamus, ovaries and testis from the summer and winter individuals were significantly higher compared with levels from the spring and autumn, whereas FSH and LH serum concentrations from summer and winter individuals were significantly lower compared with that from the spring and autumn. PRLR expression levels in hypothalamus, ovaries and testis were negatively correlated with FSH and LH serum concentrations, illustrating that PRLR might negatively regulate seasonal reproductive activity. PRLR expression levels in ovaries and testes were significantly higher compared with levels in the hypothalamus, suggesting that the regulative effects of PRLR in gonads might be significantly higher compared with that in the hypothalamus. Furthermore, PRLR expression levels from the spring, summer, autumn and winter seasons in the hypothalamus and gonads were significantly higher in females compared with levels in males, indicating that the regulative effect of PRLR might be sex dependent. Taken together, this study helps to understand in depth the seasonal regulative reproduction mechanism of striped hamsters to reasonably control population abundance.
Topics: Animals; Cricetinae; Female; Follicle Stimulating Hormone; Luteinizing Hormone; Male; Receptors, Prolactin; Reproduction; Seasons; Testis
PubMed: 34154698
DOI: 10.1017/S0967199421000095 -
Molecular and Cellular Endocrinology Jan 2014Prolactin (PRL) is a polypeptide hormone with a wide range of physiological functions, and is critical for female reproduction. PRL exerts its action by binding to... (Review)
Review
Prolactin (PRL) is a polypeptide hormone with a wide range of physiological functions, and is critical for female reproduction. PRL exerts its action by binding to membrane bound receptor isoforms broadly classified as the long form and the short form receptors. Both receptor isoforms are highly expressed in the ovary as well as in the uterus. Although signaling through the long form is believed to be more predominant, it remains unclear whether activation of this isoform alone is sufficient to support reproductive functions or whether both types of receptor are required. The generation of transgenic mice selectively expressing either the short or the long form of PRL receptor has provided insight into the differential signaling mechanisms and physiological functions of these receptors. This review describes the essential finding that both long and short receptor isoforms are crucial for ovarian functions and female fertility, and highlights novel mechanisms of action for these receptors.
Topics: Animals; Humans; Models, Biological; Prolactin; Protein Isoforms; Receptors, Prolactin; Reproduction; Signal Transduction
PubMed: 24060636
DOI: 10.1016/j.mce.2013.09.016 -
Expert Opinion on Therapeutic Targets 2015Prolactin (PRL) signaling has emerged as a relevant target in breast and prostate cancers. This has encouraged various laboratories to develop compounds targeting the... (Review)
Review
INTRODUCTION
Prolactin (PRL) signaling has emerged as a relevant target in breast and prostate cancers. This has encouraged various laboratories to develop compounds targeting the PRL receptor (PRLR). As the latter is widely distributed, it is timely to address whether other conditions could also benefit from such inhibitors.
AREAS COVERED
The authors briefly overview the two classes of PRLR blockers, which involve: i) PRL-core based analogs that have been validated as competitive antagonists in various preclinical models, and ii) anti-PRLR neutralizing antibodies that are currently in clinical Phase I for advanced breast and prostate cancers. The main purpose of this review is to discuss the multiple organs/diseases that may be considered as potential targets/indications for such inhibitors. This is done in light of reports suggesting that PRLR expression/signaling is increased in disease, and/or that systemic or locally elevated PRL levels correlate with (or promote) organ pathogenesis.
EXPERT OPINION
The two immediate challenges in the field are i) to provide the scientific community with potent anti-prolactin receptor antibodies to map prolactin receptor expression in target organs, and ii) to take advantage of the availability of functionally validated PRLR blockers to establish the relevance of these potential indications in humans.
Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Drug Design; Female; Humans; Male; Molecular Targeted Therapy; Prolactin; Prostatic Neoplasms; Receptors, Prolactin
PubMed: 26063597
DOI: 10.1517/14728222.2015.1053209 -
Current Opinion in Investigational... Apr 2005Efforts have been focused on the development of prolactin receptor (PRLR) antagonists, which, it is hoped, will be useful therapeutics for breast, prostate and possibly... (Review)
Review
Efforts have been focused on the development of prolactin receptor (PRLR) antagonists, which, it is hoped, will be useful therapeutics for breast, prostate and possibly other cancers. Several approaches have been undertaken, including the production of pure antagonists and the combination of a PRLR antagonist with other antitumor molecules to increase efficacy. An alternative approach has been the development of a mimic of the natural PRL growth antagonist. This molecule is a combined antagonist/agonist since it inhibits signaling leading to growth, but promotes signaling leading to cell-cycle control, differentiation and apoptosis.
Topics: Humans; Prolactin; Receptors, Prolactin
PubMed: 15898345
DOI: No ID Found -
Trends in Endocrinology and Metabolism:... Jun 2010Prolactin is a hormone involved in growth, development, reproduction, metabolism, water and electrolyte balance, brain and behavior, and immunoregulation. Its actions on... (Review)
Review
Prolactin is a hormone involved in growth, development, reproduction, metabolism, water and electrolyte balance, brain and behavior, and immunoregulation. Its actions on reproductive processes represent the largest group of functions identified for this hormone. Besides the classic long form of the prolactin receptor, many short form receptors have been identified in rodents and human tissues. Mouse mutagenesis studies have offered insight into the biology of the prolactin family, providing compelling evidence that different isoforms have independent biological activity. The possibility that short forms mediate cell proliferation is important for a variety of tissues including mammary glands and ovarian follicles. This review summarizes the current knowledge about prolactin signaling and its role in reproduction through either long or short isoform receptors.
Topics: Animals; Female; Gene Expression Regulation; Humans; Lactation; Mice; Prolactin; Protein Conformation; Protein Isoforms; Rats; Receptors, Prolactin; Reproduction; Second Messenger Systems; Signal Transduction
PubMed: 20149678
DOI: 10.1016/j.tem.2010.01.008