-
General and Comparative Endocrinology Apr 2023Prolactin (PRL) is a multifunctional hormone of broad physiological importance, and is involved in many aspects of fish reproduction, including the regulation of live...
Prolactin (PRL) is a multifunctional hormone of broad physiological importance, and is involved in many aspects of fish reproduction, including the regulation of live birth (viviparity) and both male and female parental care. Previous research suggests that PRL also plays an important reproductive role in syngnathid fishes (seahorses, pipefish and seadragons), a group with a highly derived reproductive strategy, male pregnancy - how the PRL axis has come to be co-opted for male pregnancy remains unclear. We investigated the molecular evolution and expression of the genes for prolactin and its receptor (PRLR) in an evolutionarily diverse sampling of syngnathid fishes to explore how the co-option of PRL for male pregnancy has impacted its evolution, and to clarify whether the PRL axis is also involved in regulating reproductive function in species with more rudimentary forms of male pregnancy. In contrast to the majority of teleost fishes, all syngnathid fishes tested carry single copies of PRL and PRLR that cluster genetically within the PRL1 and PRLRa lineages of teleosts, respectively. PRL1 gene expression in seahorses and pipefish is restricted to the pituitary, while PRLRa is expressed in all tissues, including the brood pouch of species with both rudimentary and complex brooding structures. Pituitary PRL1 expression remains stable throughout pregnancy, but PRLRa expression is specifically upregulated in the male brood pouch during pregnancy, consistent with the higher affinity of pouch tissues for PRL hormone during embryonic incubation. Finally, immunohistochemistry of brood pouch tissues reveals that both PRL1 protein and PRLRa and Na/K ATPase-positive cells line the inner pouch epithelium, suggesting that pituitary-derived PRL1 may be involved in brood pouch osmoregulation during pregnancy. Our data provide a unique molecular perspective on the evolution and expression of prolactin and its receptor during male pregnancy, and provide the foundation for further manipulative experiments exploring the role of PRL in this unique form of reproduction.
Topics: Animals; Male; Female; Prolactin; Reproduction; Fishes; Smegmamorpha; Receptors, Prolactin
PubMed: 36646326
DOI: 10.1016/j.ygcen.2023.114210 -
Frontiers in Endocrinology 2023
Topics: Prolactin; Insulin; Blood Glucose
PubMed: 37260442
DOI: 10.3389/fendo.2023.1166172 -
Animal Models and Experimental Medicine Apr 2023Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary. There are two main isoforms of PRL: 23-kDa PRL... (Review)
Review
Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary. There are two main isoforms of PRL: 23-kDa PRL (named full-length PRL) and vasoinhibins (including 5.6-18 kDa fragments). Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization, including endothelial cell proliferation and migration, protease production, and apoptosis. However, their effects on vascular function and cardiovascular diseases are different or even contrary. In addition to the structure, secretion regulation, and signal transduction of PRL/vasoinhibins, this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.
Topics: Humans; Cardiovascular Diseases; Lactotrophs; Pituitary Gland; Prolactin; Protein Isoforms
PubMed: 35923071
DOI: 10.1002/ame2.12264 -
Expert Review of Endocrinology &... Nov 2022Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been poorly investigated.
AREAS COVERED
To systematically review and analyze data from clinical studies focusing on the metabolic consequences of abnormally high prolactin levels (HPRL) and low prolactin levels (LPRL). In addition, data from preclinical studies about underlying pathophysiological mechanisms were summarized and discussed.
EXPERT OPINION
PRL contributes to providing the correct amount of energy to support the mother and the fetus/offspring during pregnancy and lactation, but it also has a homeostatic role. Pathological PRL elevation beyond these physiological conditions, but also its reduction, impairs metabolism and body composition in both genders, increasing the risk of diabetes and cardiovascular events. Hence, hypoprolactinemia should be avoided as much as possible during treatment with dopamine agonists for prolactinomas. Patients with hypoprolactinemia, because of endogenous or iatrogenic conditions, deserve, as those with hyperprolactinemia, careful metabolic assessment.
Topics: Male; Pregnancy; Humans; Female; Prolactin; Hyperprolactinemia; Prolactinoma; Pituitary Neoplasms
PubMed: 36447418
DOI: 10.1080/17446651.2022.2144829 -
Domestic Animal Endocrinology Jan 2022Prolactin is a hormone that is most important for mammary development in swine. It is also essential for both the onset and the maintenance of lactation. In early...
Prolactin is a hormone that is most important for mammary development in swine. It is also essential for both the onset and the maintenance of lactation. In early studies, exogenous recombinant porcine prolactin was used to detect its biological effects on mammary tissue. In these studies, a stimulatory role of prolactin for mammary development of prepubertal gilts was demonstrated. However, when injected throughout lactation, prolactin did not increase sow milk yield likely because mammary receptors were saturated. The secretion of prolactin is largely under negative regulation via dopamine. Inhibition studies using the dopamine agonist bromocriptine showed that prolactin is required in the last third of gestation to sustain mammary development in gilts. When creating a hyperprolactinemic state during that same period, with the dopamine antagonist domperidone, differentiation of mammary epithelial cells was stimulated and milk yield in the subsequent lactation was increased. Domperidone given throughout lactation also led to greater milk yield. A study using domperidone in prepubertal gilts, however, did not reproduce the stimulatory effect of exogenous prolactin on mammary development and demonstrated that timing of the prolactin increase in relation to age of the animals is most important to elicit a response on mammary tissue. Attempts were made to use feed ingredients such as the plant extract from milk thistle, sylimarin, to stimulate prolactin secretion in sows. However, even though prolactin concentrations were increased, this augmentation was not important enough to have an impact on mammary development in late gestation or to increase milk yield. The current knowledge that hyperprolactinemia has beneficial effects for mammary development at various physiological stages and can enhance milk yield in swine leads to new avenues in elaborating strategies that could be used at the farm level to improve sow lactation performance.
Topics: Animals; Female; Hyperprolactinemia; Lactation; Mammary Glands, Animal; Milk; Pregnancy; Prolactin; Sus scrofa; Swine; Swine Diseases
PubMed: 34530351
DOI: 10.1016/j.domaniend.2021.106672 -
Hormone Molecular Biology and Clinical... Mar 2023Patients with type 1 diabetes mellitus have been reported to have elevated prolactin levels and a possible relationship between prolactin levels and the development of... (Review)
Review
OBJECTIVES
Patients with type 1 diabetes mellitus have been reported to have elevated prolactin levels and a possible relationship between prolactin levels and the development of the disease has been proposed. However, some studies show that prolactin mediates beneficial functions in beta cells. Therefore, we review information on the roles of prolactin in type 1 diabetes mellitus.
CONTENT
Here we summarize the functions of prolactin in the immune system and in pancreatic beta cells, in addition, we describe studies related to PRL levels, its regulation and alterations of secretion in patients with type 1 diabetes mellitus.
SUMMARY
Studies in murine models have shown that prolactin protects beta cells from apoptosis, stimulates their proliferation and promotes pancreatic islet revascularization. In addition, some studies in patients with type 1 diabetes mellitus have shown that elevated prolactin levels correlate with better disease control.
OUTLOOK
Prolactin treatment appears to be a promising strategy to improve beta-cell vascularization and proliferation in transplantation and immunotherapies.
Topics: Mice; Humans; Animals; Diabetes Mellitus, Type 1; Prolactin; Insulin-Secreting Cells; Immune System
PubMed: 35852366
DOI: 10.1515/hmbci-2022-0008 -
Orphanet Journal of Rare Diseases Nov 2023Tetrahydrobiopterin (BH) deficiency caused by 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is a rare disorder that is one of the major causes of... (Review)
Review
BACKGROUND
Tetrahydrobiopterin (BH) deficiency caused by 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is a rare disorder that is one of the major causes of hyperphenylalaninemia in Taiwan.
METHODS
In this study, we reviewed the clinical courses of 12 adolescent and adult patients (7 females and 5 males) with PTPS deficiency.
RESULTS
The patients were treated shortly after diagnosis through newborn screening with a combination of BH, levodopa/carbidopa, and 5-OH-tryptophan. Their plasma phenylalanine and tyrosine levels were well controlled, and their prolactin levels were also decreased after treatment. However, their prolactin levels gradually rose as they grew into puberty, and at a current age of 27.5 [interquartile range (IQR 7.9)] years, five of the 12 patients had either highly elevated prolactin levels (> 100 ng/mL in one male patient, normal reference values, male < 11 ng/mL, female < 17 ng/mL) or symptoms, including irregular menstruation, amenorrhea, and breast swelling (in four female patients). The dosage of levodopa in these five patients (14.3 (IQR 3.0) mg/kg/day) was slightly higher than that in the other patients (p = 0.05). Magnetic resonance imaging studies did not reveal an increase in the size of the anterior pituitary gland, although a Rathke cleft cyst was found in one patient. Two patients received cabergoline treatment, which promptly lowered prolactin levels and relieved symptoms.
CONCLUSIONS
Hyperprolactinemia is common in female patients with PTPS deficiency, especially after puberty. A long-acting dopamine agonist, such as cabergoline, may be a necessary adjunctive treatment for most patients with BH deficiency.
Topics: Adolescent; Adult; Female; Humans; Infant, Newborn; Male; Cabergoline; Hyperprolactinemia; Levodopa; Phenylketonurias; Prolactin
PubMed: 37950276
DOI: 10.1186/s13023-023-02963-4 -
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 -
Best Practice & Research. Clinical... Dec 2019Nowadays, more than 80 autoimmune disorders are recognized, in which an aberrant immune response against different organs and tissues plays a crucial role. Hormonal... (Review)
Review
Nowadays, more than 80 autoimmune disorders are recognized, in which an aberrant immune response against different organs and tissues plays a crucial role. Hormonal homeostasis has great influence in achieving competent and healthy immune system function. Prolactin has a bioactive function acting as a hormone and a cytokine. It influences the immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Hyperprolactinemia has been detected in many patients with different autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, multiple sclerosis, autoimmune thyroid disease, systemic sclerosis, among others, and its believed to play a crucial role in disease pathogenesis. A direct correlation between prolactin levels and disease activity was not clear. Genetic factors may have a role in humans as in animal models. Dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, the authors attempt to provide a critical overview on the role of prolactin in the immune system, exploring its contribution to the development of autoimmune diseases.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Cytokines; Humans; Hyperprolactinemia; Immune System; Inflammation Mediators; Lupus Erythematosus, Systemic; Prolactin
PubMed: 31564625
DOI: 10.1016/j.beem.2019.101324 -
Endocrinology Oct 2022The pathogenesis of breast cancer is driven by multiple hormones and growth factors. One of these, prolactin (PRL), contributes to both mammary differentiation and... (Review)
Review
The pathogenesis of breast cancer is driven by multiple hormones and growth factors. One of these, prolactin (PRL), contributes to both mammary differentiation and oncogenesis, and yet the basis for these disparate effects has remained unclear. The focus of this review is to examine and place into context 2 recent studies that have provided insight into the roles of PRL receptors and PRL in tumorigenesis and tumor progression. One study provides novel evidence for opposing actions of PRL in the breast being mediated in part by differential PRL receptor (PRLr) isoform utilization. Briefly, homomeric complexes of the long isoform of the PRLr (PRLrL-PRLrL) promotes mammary differentiation, while heteromeric complexes of the intermediate and long PRLr (PRLrI-PRLrL) isoforms trigger mammary oncogenesis. Another study describes an immunodeficient, prolactin-humanized mouse model, NSG-Pro, that facilitates growth of PRL receptor-expressing patient-derived breast cancer xenografts. Evidence obtained with this model supports the interactions of physiological levels of PRL with estrogen and ERBB2 gene networks, the modulatory effects of PRL on drug responsiveness, and the pro-metastatic effects of PRL on breast cancer. This recent progress provides novel concepts, mechanisms and experimental models expected to renew interest in harnessing/exploiting PRLr signaling for therapeutic effects in breast cancer.
Topics: Animals; Breast Neoplasms; Cell Transformation, Neoplastic; Female; Humans; Mice; Prolactin; Protein Isoforms; Receptors, Prolactin
PubMed: 35922139
DOI: 10.1210/endocr/bqac122