Variant Prolactin Receptor in Agalactia and Hyperprolactinemia

Kobayashi, Tatsuya; Usui, Hirokazu; Tanaka, Hirokazu; Shozu, Makio

doi:10.1056/nejmoa1805171

Cited by 27 publications

(13 citation statements)

References 17 publications

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“…While loss of the Prlr leads to large pituitary tumors in mice, homozygous loss-of-function PRLR mutation in a human patient with hyperprolactinemia and agalactia had no pituitary tumor ( 100 ). On the contrary, a gain-of-function variant was identified in 9 out of 46 patients with PRL-PTs, representing a possible novel mechanism for prolactinoma tumorigenesis.…”

Section: Genetic Mechanisms Of Tumorigenesismentioning

confidence: 99%

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

Nadhamuni

Korbonits

2020

Endocrine Reviews

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Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or non-syndromic conditions with pituitary tumor predisposition. These include the identification of novel germline variants in patients with familial or simplex pituitary tumors and establishment of novel somatic variants identified through next generation sequencing. Advanced techniques have allowed the exploration of epigenetic mechanisms mediated through DNA methylation, histone modifications and non-coding RNAs, such as microRNA, long noncoding RNAs and circular RNAs. These mechanisms can influence tumor formation, growth and invasion. While genetic and epigenetic mechanisms often disrupt similar pathways, such as cell cycle regulation, in pituitary tumors there is little overlap between genes altered by germline, somatic and epigenetic mechanisms. The interplay between these complex mechanisms driving tumorigenesis are best studied in the emerging multi-omics studies. Here, we summarize insights from the recent developments in the regulation of pituitary tumorigenesis.

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Section: Genetic Mechanisms Of Tumorigenesismentioning

confidence: 99%

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

Nadhamuni

Korbonits

2020

Endocrine Reviews

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“…Another case of compound LoF mutations (nonsense R171Ter) and missense (P269L) mutations in the human RPLR was recently reported [138]. In this case, the proband's mother and father were heterozygous for the R171Ter and P269L mutations.…”

Section: Prolactin Receptor (Prlr)mentioning

confidence: 83%

“…In this case, the proband's mother and father were heterozygous for the R171Ter and P269L mutations. The proband suffered from hyperprolactinemia associated with postpartum agalactia, and the mother who carried the heterozygous R171Ter mutation reported insufficient human milk production after her pregnancies, but was successful in breastfeeding when combined with the addition of baby formula until three months post-partum [138]. These findings strongly suggest that homozygous LoF mutations or heterozygous mutations in RPLR may have a prominent influence on lactation outcomes and that the prevalence of such mutations in the population should be examined for early diagnosis and support of women that carry these mutations during breastfeeding.…”

Section: Prolactin Receptor (Prlr)mentioning

confidence: 99%

Genetic and Physiological Factors Affecting Human Milk Production and Composition

Golan

Assaraf

2020

Nutrients

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Human milk is considered the optimal nutrition for infants as it provides additional attributes other than nutritional support for the infant and contributes to the mother’s health as well. Although breastfeeding is the most natural modality to feed infants, nowadays, many mothers complain about breastfeeding difficulties. In addition to environmental factors that may influence lactation outcomes including maternal nutrition status, partner’s support, stress, and latching ability of the infant, intrinsic factors such as maternal genetics may also affect the quantitative production and qualitative content of human milk. These genetic factors, which may largely affect the infant’s growth and development, as well as the mother’s breastfeeding experience, are the subject of the present review. We specifically describe genetic variations that were shown to affect quantitative human milk supply and/or its qualitative content. We further discuss possible implications and methods for diagnosis as well as treatment modalities. Although cases of nutrient-deficient human milk are considered rare, in some ethnic groups, genetic variations that affect human milk content are more abundant, and they should receive greater attention for diagnosis and treatment when necessary. From a future perspective, early genetic diagnosis should be directed to target and treat breastfeeding difficulties in real time.

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“…Prolactin (PRL) is a multifunctional hormone which is synthesized and secreted by pituitary [1]. Human PRL gene is located on chromosome 6 [2].…”

Section: Introductionmentioning

confidence: 99%

“…The concentration of PRL in human serum has a certain reference range, and when its concentration is too high or too low, it will have a certain impact on the body. Dopamine can inhibit the secretion of PRL, and there are cases where dopamine is used to treat hyperprolactinemia [1]. PRL's biological functions include production, growth, development, immunoregulation, and metabolism [5,6].…”

Section: Introductionmentioning

confidence: 99%

Prolactin Proteoform Pattern Changed in Human Pituitary Adenoma Relative to Control Pituitary Tissues

Zhan¹,

Qian²

2020

Proteoforms - Concept and Applications in Medical Sciences

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PRL gene-encoded prolactin is synthesized in the ribosome in the pituitary and then secretes into blood circulation to reach its target organ and exerts its biological roles, for example, involving in production, growth, development, immunoregulation, and metabolism. Multiple post-translational modifications and other unknown factors might be involved in this process to cause different prolactin proteoforms with differential isoelectric point (pI) and relative mass (M r). Pituitary adenomas are the common disease occurring in pituitary organ to affect the endocrine system. Two-dimensional gel electrophoresis (2DGE) was used to separate prolactin proteoforms according to their pI and M r , followed by identification with Western blot and mass spectrometry (MS) analyses. Six prolactin proteoforms were identified in control pituitary tissues, and this prolactin proteoform pattern was significantly changed in different hormone subtypes of nonfunctional pituitary adenomas (NF − , LH + , FSH + , and LH + / FSH +) and prolactinomas (PRL +). Further, bioinformatics analysis revealed that different prolactin proteoforms might bind to different short-or long-PRL receptor-mediated signaling pathways. These findings clearly demonstrated that prolactin proteoform pattern existed in human pituitary and changed in different subtypes of pituitary adenomas. It is the scientific data to in-depth study prolactin functions, and to discover the prolactin proteoform biomarkers for PRL-related adenomas.

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Variant Prolactin Receptor in Agalactia and Hyperprolactinemia

Cited by 27 publications

References 17 publications

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

Novel Insights into Pituitary Tumorigenesis: Genetic and Epigenetic Mechanisms

Genetic and Physiological Factors Affecting Human Milk Production and Composition

Prolactin Proteoform Pattern Changed in Human Pituitary Adenoma Relative to Control Pituitary Tissues

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