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Archives of Endocrinology and Metabolism 2016Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect... (Review)
Review
Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin's functions through several signaling pathways, although the recruitment of the signal transducer and activator of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, we will summarize the current knowledge about prolactin's actions on reproduction. Among other aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat prolactin-induced infertility.
Topics: Female; Humans; Hyperprolactinemia; Hypothalamus; Infertility; Kisspeptins; Male; Prolactin; Receptors, Prolactin; Reproduction; Sex Factors; Signal Transduction
PubMed: 27901187
DOI: 10.1590/2359-3997000000230 -
Neuroendocrinology 2022Converging evidence indicates prolactin (PRL) and diabetes play an important role in the pathophysiology of cognitive impairment. However, little is known about the... (Review)
Review
BACKGROUND
Converging evidence indicates prolactin (PRL) and diabetes play an important role in the pathophysiology of cognitive impairment. However, little is known about the mechanisms responsible for the effects of PRL and diabetes on cognitive impairment.
SUMMARY
We summarize and review the available literature and current knowledge of the association between PRL and diabetes on aspects of cognitive impairment.
KEY MESSAGES
The phosphatidylinositol 3-kinase/protein kinase B pathway is central to the molecular mechanisms underlying how PRL and diabetes interact in cognitive impairment. Further work is needed to identify the interaction between PRL and diabetes, especially in the molecular aspects of cognitive impairment, which can suggest novel strategies for cognitive dysfunction treatment.
Topics: Cognitive Dysfunction; Diabetes Mellitus; Humans; Prolactin; Receptors, Prolactin
PubMed: 34963126
DOI: 10.1159/000521653 -
International Journal of Environmental... Feb 2023The most important and widely studied role of prolactin (PRL) is its modulation of stress responses during pregnancy and lactation. PRL acts as a neuropeptide to support... (Review)
Review
The most important and widely studied role of prolactin (PRL) is its modulation of stress responses during pregnancy and lactation. PRL acts as a neuropeptide to support physiological reproductive responses. The effects of PRL on the nervous system contribute to a wide range of changes in the female brain during pregnancy and the inhibition of the hypothalamic-pituitary axis. All these changes contribute to the behavioral and physiological adaptations of a young mother to enable reproductive success. PRL-driven brain adaptations are also crucial for regulating maternal emotionality and well-being. Hyperprolactinemia (elevated PRL levels) is a natural and beneficial phenomenon during pregnancy and lactation. However, in other situations, it is often associated with serious endocrine disorders, such as ovulation suppression, which results in a lack of offspring. This introductory example shows how complex this hormone is. In this review, we focus on the different roles of PRL in the body and emphasize the results obtained from animal models of neuropsychiatric disorders.
Topics: Pregnancy; Animals; Female; Prolactin; Hyperprolactinemia; Lactation
PubMed: 36833950
DOI: 10.3390/ijerph20043257 -
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 -
General and Comparative Endocrinology Jul 2014The peptide hormone prolactin is a functionally versatile hormone produced by the vertebrate pituitary. Comparative studies over the last six decades have revealed that... (Review)
Review
The peptide hormone prolactin is a functionally versatile hormone produced by the vertebrate pituitary. Comparative studies over the last six decades have revealed that a conserved function for prolactin across vertebrates is the regulation of ion and water transport in a variety of tissues including those responsible for whole-organism ion homeostasis. In teleost fishes, prolactin was identified as the "freshwater-adapting hormone", promoting ion-conserving and water-secreting processes by acting on the gill, kidney, gut and urinary bladder. In mammals, prolactin is known to regulate renal, intestinal, mammary and amniotic epithelia, with dysfunction linked to hypogonadism, infertility, and metabolic disorders. Until recently, our understanding of the cellular mechanisms of prolactin action in fishes has been hampered by a paucity of molecular tools to define and study ionocytes, specialized cells that control active ion transport across branchial and epidermal epithelia. Here we review work in teleost models indicating that prolactin regulates ion balance through action on ion transporters, tight-junction proteins, and water channels in ionocytes, and discuss recent advances in our understanding of ionocyte function in the genetically and embryonically accessible zebrafish (Danio rerio). Given the high degree of evolutionary conservation in endocrine and osmoregulatory systems, these studies in teleost models are contributing novel mechanistic insight into how prolactin participates in the development, function, and dysfunction of osmoregulatory systems across the vertebrate lineage.
Topics: Animals; Endocrine System; Epithelial Cells; Gills; Osmoregulation; Prolactin; Water-Electrolyte Balance; Zebrafish
PubMed: 24434597
DOI: 10.1016/j.ygcen.2013.12.014 -
American Journal of Physiology.... Nov 2015The hormonal family of vasoinhibins, which derive from the anterior pituitary hormone prolactin, are known for their inhibiting effects on blood vessel growth,... (Review)
Review
The hormonal family of vasoinhibins, which derive from the anterior pituitary hormone prolactin, are known for their inhibiting effects on blood vessel growth, vasopermeability, and vasodilation. As pleiotropic hormones, vasoinhibins act in multiple target organs and tissues. The generation, secretion, and regulation of vasoinhibins are embedded into the organizational principle of an axis, which integrates the hypothalamus, the pituitary, and the target tissue microenvironment. This axis is designated as the prolactin/vasoinhibin axis. Disturbances of the prolactin/vasoinhibin axis are associated with the pathogenesis of retinal and cardiac diseases and with diseases occurring during pregnancy. New phylogenetical, physiological, and clinical implications are discussed.
Topics: Animals; Cell Cycle Proteins; Gene Expression Regulation; Humans; Neovascularization, Physiologic; Prolactin
PubMed: 26310939
DOI: 10.1152/ajpregu.00256.2015 -
Frontiers in Endocrinology 2022The term inflammatory arthritis defines a family of diseases, including rheumatoid arthritis (RA), caused by an overactive immune system, and influenced by host aspects... (Review)
Review
The term inflammatory arthritis defines a family of diseases, including rheumatoid arthritis (RA), caused by an overactive immune system, and influenced by host aspects including sex, reproductive state, and stress. Prolactin (PRL) is a sexually dimorphic, reproductive, stress-related hormone long-linked to RA under the general assumption that it aggravates the disease. However, this conclusion remains controversial since PRL has both negative and positive outcomes in RA that may depend on the hormone circulating levels, synthesis by joint tissues, and complex interactions at the inflammatory milieu. The inflamed joint is rich in matrix metalloproteases that cleave PRL to vasoinhibin, a PRL fragment with proinflammatory effects and the ability to inhibit the hyperpermeability and growth of blood vessels. This review addresses this field with the idea that explanatory mechanisms lie within the PRL/vasoinhibin axis, an integrative framework influencing not only the levels of systemic and local PRL, but also the proteolytic conversion of PRL to vasoinhibin, as vasoinhibin itself has dual actions on joint inflammation. In this review, we discuss recent findings from mouse models suggesting the upregulation of endogenous vasoinhibin by the pro-inflammatory environment and showing dichotomous actions and signaling mechanisms of PRL and vasoinhibin on joint inflammation that are cell-specific and context-dependent. We hypothesize that these opposing actions work together to balance the inflammatory response and provide new insights for understanding the pathophysiology of RA and the development of new treatments.
Topics: Animals; Arthritis, Rheumatoid; Inflammation; Mice; Prolactin; Protein Binding
PubMed: 35721729
DOI: 10.3389/fendo.2022.905756 -
Fertility and Sterility Feb 1997To review the pathophysiology, clinical manifestations, current diagnostic procedures, and treatment options for disorders involving PRL production. Common clinical... (Review)
Review
OBJECTIVE
To review the pathophysiology, clinical manifestations, current diagnostic procedures, and treatment options for disorders involving PRL production. Common clinical dilemmas are discussed in a pragmatic fashion to guide the practitioner.
DESIGN
A world literature search of basic sciences and medical articles from the last three decades was performed using computerized MEDLINE. Recent endocrine and reproductive endocrine textbooks also were reviewed. Studies were selected for their degree of contribution to the basic sciences and clinical understanding of the disorder and for the quality of their study design and content. The information was summarized and grouped according to its relevance and application to specific sections of the manuscript. Studies were evaluated and critically used to support the views of the authors and to suggest specific clinical management strategies.
RESULT(S)
Disorders derived from abnormal PRL production are relatively common in clinical practice. Infertility, menstrual disorders, and galactorrhea are the most frequent manifestations encountered in women. Although frequently benign, the disorder occasionally may have severe consequences.
CONCLUSION(S)
An understanding of the underlying physiology and pathophysiology coupled with the awareness of the heterogeneous presentation of this disorder should help the clinician to approach it successfully.
Topics: Animals; Endocrine System Diseases; Female; Galactorrhea; Humans; Infertility, Female; Menstruation Disturbances; Prolactin
PubMed: 9022592
DOI: 10.1016/S0015-0282(97)81900-0 -
Revista Da Associacao Medica Brasileira... 2015The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also... (Review)
Review
The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.
Topics: Animals; Blastocyst; Cell Proliferation; Embryo Implantation; Female; Humans; Melatonin; Photoperiod; Pineal Gland; Pregnancy; Prolactin; Reproduction
PubMed: 26248251
DOI: 10.1590/1806-9282.61.03.269 -
Frontiers in Endocrinology 2022Breast cancer is a major disease affecting women worldwide. A woman has 1 in 8 lifetime risk of developing breast cancer, and morbidity and mortality due to this disease... (Review)
Review
Breast cancer is a major disease affecting women worldwide. A woman has 1 in 8 lifetime risk of developing breast cancer, and morbidity and mortality due to this disease are expected to continue to rise globally. Breast cancer remains a challenging disease due to its heterogeneity, propensity for recurrence and metastasis to distant vital organs including bones, lungs, liver and brain ultimately leading to patient death. Despite the development of various therapeutic strategies to treat breast cancer, still there are no effective treatments once metastasis has occurred. Loss of differentiation and increased cellular plasticity and stemness are being recognized molecularly and clinically as major derivers of heterogeneity, tumor evolution, relapse, metastasis, and therapeutic failure. In solid tumors, breast cancer is one of the leading cancer types in which tumor differentiation state has long been known to influence cancer behavior. Reprograming and/or restoring differentiation of cancer cells has been proposed to provide a viable approach to reverse the cancer through differentiation and terminal maturation. The hormone prolactin (PRL) is known to play a critical role in mammary gland lobuloalveolar development/remodeling and the terminal differentiation of the mammary epithelial cells promoting milk proteins gene expression and lactation. Here, we will highlight recent discoveries supporting an anti-tumorigenic role for PRL in breast cancer as a "pro/forward-differentiation" pathway restricting plasticity, stemness and tumorigenesis.
Topics: Breast Neoplasms; Carcinogenesis; Female; Humans; Milk Proteins; Neoplasm Recurrence, Local; Prolactin
PubMed: 36157462
DOI: 10.3389/fendo.2022.993570