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Frontiers in Global Women's Health 2021Transition into motherhood involves profound physiological and behavioral adaptations that ensure the healthy development of offspring while maintaining maternal health.... (Review)
Review
Transition into motherhood involves profound physiological and behavioral adaptations that ensure the healthy development of offspring while maintaining maternal health. Dynamic fluctuations in key hormones during pregnancy and lactation induce these maternal adaptations by acting on neural circuits in the brain. Amongst these hormonal changes, lactogenic hormones (e.g., prolactin and its pregnancy-specific homolog, placental lactogen) are important regulators of these processes, and their receptors are located in key brain regions controlling emotional behaviors and maternal responses. With pregnancy and lactation also being associated with a marked elevation in the risk of developing mood disorders, it is important to understand how hormones are normally regulating mood and behavior during this time. It seems likely that pathological changes in mood could result from aberrant expression of these hormone-induced behavioral responses. Maternal mental health problems during pregnancy and the postpartum period represent a major barrier in developing healthy mother-infant interactions which are crucial for the child's development. In this review, we will examine the role lactogenic hormones play in driving a range of specific maternal behaviors, including motivation, protectiveness, and mother-pup interactions. Understanding how these hormones collectively act in a mother's brain to promote nurturing behaviors toward offspring will ultimately assist in treatment development and contribute to safeguarding a successful pregnancy.
PubMed: 34927138
DOI: 10.3389/fgwh.2021.767467 -
Proceedings of the National Academy of... Feb 2022Aggressive behavior is rarely observed in virgin female mice but is specifically triggered in lactation where it facilitates protection of offspring. Recent studies...
Aggressive behavior is rarely observed in virgin female mice but is specifically triggered in lactation where it facilitates protection of offspring. Recent studies demonstrated that the hypothalamic ventromedial nucleus (VMN) plays an important role in facilitating aggressive behavior in both sexes. Here, we demonstrate a role for the pituitary hormone, prolactin, acting through the prolactin receptor in the VMN to control the intensity of aggressive behavior exclusively during lactation. Prolactin receptor deletion from glutamatergic neurons or specifically from the VMN resulted in hyperaggressive lactating females, with a marked shift from intruder-directed investigative behavior to very high levels of aggressive behavior. Prolactin-sensitive neurons in the VMN project to a wide range of other hypothalamic and extrahypothalamic regions, including the medial preoptic area, paraventricular nucleus, and bed nucleus of the stria terminalis, all regions known to be part of a complex neuronal network controlling maternal behavior. Within this network, prolactin acts in the VMN to specifically restrain male-directed aggressive behavior in lactating females. This action in the VMN may complement the role of prolactin in other brain regions, by shifting the balance of maternal behaviors from defense-related activities to more pup-directed behaviors necessary for nurturing offspring.
Topics: Aggression; Animals; Female; Hypothalamus; Lactation; Male; Maternal Behavior; Mice; Mice, Inbred C57BL; Neurons; Paraventricular Hypothalamic Nucleus; Preoptic Area; Prolactin; Receptors, Prolactin; Thalamus; Ventromedial Hypothalamic Nucleus
PubMed: 35131854
DOI: 10.1073/pnas.2116972119 -
Indian Journal of Dermatology 2018Studying the link between prolactin and autoimmunity has gained much ground over the past years. Its role played in alopecia areata (AA) is not clear yet, as previous...
CONTEXT
Studying the link between prolactin and autoimmunity has gained much ground over the past years. Its role played in alopecia areata (AA) is not clear yet, as previous reports yielded controversial results.
AIMS
This study aimed to measure the serum level of prolactin and to detect the expression of its receptor in AA, in an attempt to highlight its possible role in the pathogenesis of this disease.
SUBJECTS AND METHODS
A case-control study of 30 AA patients and 20 controls from outpatient clinic were undertaken. Every patient was subjected to history taking and clinical examination to determine the severity of alopecia tool (SALT) score. Blood samples were taken from patients and controls to determine the serum prolactin level. Scalp biopsies were obtained from the lesional skin of patients and normal skin of controls for assessment of the prolactin receptor.
STATISTICAL ANALYSIS
Depending upon the type of data, -test, analysis of variance test, Chi-square, receiver operator characteristic curve were undertaken.
RESULTS
On comparing the serum prolactin level between patients and controls, no significant difference was found, while the mean tissue level of prolactin receptor was significantly higher in patients than in controls. In patients, a significant positive correlation was found between the prolactin receptor and the SALT score.
CONCLUSIONS
Prolactin plays a role in AA, and this role is probably through the prolactin receptors rather than the serum prolactin level.
PubMed: 29937561
DOI: 10.4103/ijd.IJD_590_17 -
Current Opinion in Obstetrics &... Aug 2019To briefly summarize what is known regarding hyperprolactinemia and prolactin-secreting tumors, and review recent findings. (Review)
Review
PURPOSE OF REVIEW
To briefly summarize what is known regarding hyperprolactinemia and prolactin-secreting tumors, and review recent findings.
RECENT FINDINGS
Prolactin was previously thought to inhibit secretion of gonadotropin-releasing hormone (GnRH) by directly inhibiting the firing of GnRH neurons, resulting in hypogonadotropic hypogonadism and infertility. However, kisspeptin has recently been implicated as the mediator of hyperprolactinemia-induced infertility, by acting upstream of the GnRH neurons as an integrator of endocrine signals.Macroprolactin is generally considered to be inactive and clinically insignificant, but new studies have suggested that patients with macroprolactinemia may have reproductive manifestations as well as sexual dysfunction.Several mutations and polymorphisms in the prolactin receptor have been described, which could describe a genetic cause for prolactinomas and characterize cases of isolated familial hyperprolactinemia.Kisspeptin and tyrosine kinase inhibitors have emerged as potential new therapeutic targets for the treatment of hyperprolactinemia and dopamine-resistant prolactinomas.
SUMMARY
Molecular studies are shedding light on the pathophysiology of hyperprolactinemia and the effects of excess prolactin production on the reproductive system. Similarly, genetic studies have begun to reveal how differences in prolactin receptor function may account for some of the previously 'idiopathic' cases of hyperprolactinemia and bring to light new causes of prolactinomas. Further elucidation of the transcriptional pathways affected by these genetic changes may help to create new therapeutic targets.
Topics: Animals; Female; Genetic Variation; Genomics; Gonadotropin-Releasing Hormone; Humans; Hyperprolactinemia; Infertility; Kisspeptins; Male; Mice; Mice, Transgenic; Neurons; Prolactin; Protein-Tyrosine Kinases; Receptors, Prolactin; Reproduction
PubMed: 31045655
DOI: 10.1097/GCO.0000000000000545 -
Trends in Neurosciences Aug 2020Women experience many pain conditions more frequently when compared with men, but the biological mechanisms underlying sex differences in pain remain poorly understood.... (Review)
Review
Women experience many pain conditions more frequently when compared with men, but the biological mechanisms underlying sex differences in pain remain poorly understood. In particular, little is known about possible sex differences in peripheral nociceptors, the fundamental building blocks of pain transmission. Emerging evidence reveals that prolactin (PRL) signaling at its cognate prolactin receptor (PRLR) in primary afferents promotes nociceptor sensitization and pain in a female-selective fashion. In this review, we summarize recent progress in understanding the female-selective role of PRL/PRLR in nociceptor sensitization and in pathological pain conditions, including postoperative, inflammatory, neuropathic, and migraine pain, as well as opioid-induced hyperalgesia. The clinical implications of the peripheral PRL/PRLR system for the discovery of new therapies for pain control in women are also discussed.
Topics: Female; Humans; Hyperalgesia; Male; Nociceptors; Pain; Prolactin; Receptors, Prolactin
PubMed: 32620290
DOI: 10.1016/j.tins.2020.06.003 -
Frontiers in Endocrinology 2022The hypothalamic neuroendocrine catecholamine dopamine regulates the lactotroph function, including prolactin (PRL) secretion, proliferation, and apoptosis. The... (Review)
Review
The hypothalamic neuroendocrine catecholamine dopamine regulates the lactotroph function, including prolactin (PRL) secretion, proliferation, and apoptosis. The treatment of PRL-secreting tumors, formerly known as prolactinomas, has relied mainly on this physiological characteristic, making dopamine agonists the first therapeutic alternative. Nevertheless, the group of patients that do not respond to this treatment has few therapeutical options. Prolactin is another physiological regulator of lactotroph function, acting as an autocrine/paracrine factor that controls PRL secretion and cellular turnover, inducing apoptosis and decreasing proliferation. Furthermore, the signaling pathways related to these effects, mainly JAK/STAT and PI3K/Akt, and MAPK, have been extensively studied in prolactinomas and other tumors as therapeutic targets. In the present work, the relationship between PRL pathophysiology and prolactinoma development is explored, aiming to comprehend the value of PRL and PRLR-associated pathways as exploratory fields alternative to dopamine-related approaches, which are worth physiological characteristics that might be impaired and can be potentially restored or upregulated to provide more options to the patients.
Topics: Humans; Prolactinoma; Receptors, Prolactin; Dopamine; Prolactin; Pituitary Neoplasms; Phosphatidylinositol 3-Kinases
PubMed: 36714572
DOI: 10.3389/fendo.2022.1057749 -
Reproductive Sciences (Thousand Oaks,... Sep 2022Uterine leiomyomas are benign, estrogen-sensitive, fibrotic smooth muscle cell tumors occurring in the uterine myometrium. Leiomyomas are a considerable health burden,...
Uterine leiomyomas are benign, estrogen-sensitive, fibrotic smooth muscle cell tumors occurring in the uterine myometrium. Leiomyomas are a considerable health burden, with a lifetime prevalence of 80% and limited treatment options. Estrogen and progesterone have positive effects on leiomyoma growth, but little is known about the roles of other hormones. One hormone of interest is prolactin, as it has been described to be present and functional in leiomyomas. The current study investigates prolactin production within leiomyomas and its effects on myometrial cells. RNA isolation and quantitative-PCR of human leiomyoma samples relative to matched adjacent myometrium confirms significant expression of prolactin and dopamine receptor D2, a known regulator of prolactin production and release in the pituitary, with no difference in prolactin receptor expression. Immunohistochemistry confirms increased prolactin in leiomyomas compared to adjacent myometrium and uteri from women without leiomyomas. These results suggest that leiomyomas contain cells that produce prolactin, which may then promote signaling in leiomyoma cells to regulate leiomyoma development/growth. Accordingly, we find that prolactin robustly activates STAT5 and MAPK signaling in rat and human myometrial cell lines. Furthermore, prolactin stimulates expression of myofibroblast markers in rat myometrial cells. Our findings suggest that local prolactin production in leiomyomas may stimulate trans-differentiation of myometrial cells to myofibroblasts, which in turn contributes to the fibrotic nature of leiomyomas.
Topics: Animals; Estrogens; Female; Fibrosis; Humans; Leiomyoma; Myometrium; Prolactin; Rats; Uterine Neoplasms
PubMed: 34724171
DOI: 10.1007/s43032-021-00741-w -
General and Comparative Endocrinology Jan 2021The hormone prolactin has many diverse functions across taxa such as osmoregulation, metabolism, and reproductive behavior. In ring doves, central prolactin action is...
The hormone prolactin has many diverse functions across taxa such as osmoregulation, metabolism, and reproductive behavior. In ring doves, central prolactin action is important for parental care and feeding behavior. However, there is a considerable lack of information on the distribution of the prolactin receptor (PRLR) in the avian CNS to test the hypothesis that prolactin mediates these and other functions in other birds. In order to advance this research, we collected brains from breeding and non-breeding zebra finches to map the PRLR distribution using immunohistochemistry. We found PRLRs are distributed widely across the brain, both in hypothalamic sites known to regulate parental care and feeding, but also in many non-hypothalamic sites, including the tectofugal visual pathway, song system regions, reward associated areas, and pallium. This raises the possibility that prolactin has other functions throughout the brain that are not necessarily related to feeding or parental care. In addition, we also stained brains for pSTAT5, a transcription factor which is expressed when the PRLR is activated and is used as a marker for PRLR activity. We found several notable differences in pSTAT5 activity due to the breeding state of the animal, in both directions, further supporting the hypothesis that prolactin has many diverse functions in the brain both within and outside times of breeding. Together, this study represents the first essential step to inform the design of causative studies which manipulate PRLR-expressing cells to test their role in a wide variety of behaviors and other physiological functions.
Topics: Animals; Breeding; Finches; Gene Expression Regulation; Prolactin; Receptors, Prolactin; Reproduction
PubMed: 33159912
DOI: 10.1016/j.ygcen.2020.113657 -
Seminars in Cell & Developmental Biology Jun 2021Prolactin has a rich mechanistic set of actions and signaling in order to elicit developmental effects in mammals. Historically, prolactin has been appreciated as an... (Review)
Review
Prolactin has a rich mechanistic set of actions and signaling in order to elicit developmental effects in mammals. Historically, prolactin has been appreciated as an endocrine peptide hormone that is responsible for final, functional mammary gland development and lactation. Multiple signaling pathways impacted upon by the microenvironment contribute to cell function and differentiation. Endocrine, autocrine and paracrine signaling are now apparent in not only mammary development, but also in cancer, and involve multiple cell types including those of the immune system. Multiple ligands agonists are capable of binding to the prolactin receptor, potentially expanding receptor function. Prolactin has an important role not only in tumorigenesis of the breast, but also in a number of hormonally responsive cancers such as prostate, ovarian and endometrial cancer, as well as pancreatic and lung cancer. Although pituitary and extra-pituitary sources of prolactin such as the epithelium are important, stromal sourced prolactin is now also being recognized as an important factor in tumor progression, all of which potentially signal to multiple cell types in the tumor microenvironment. While prolactin has important roles in milk production including calcium and bone homeostasis, in the disease state it can also affect bone homeostasis. Prolactin also impacts metastatic cancer of the breast to modulate the bone microenvironment and promote bone damage. Prolactin has a fascinating contribution in both physiologic and pathologic settings of mammals.
Topics: Animals; Disease Models, Animal; Female; Humans; Mammary Glands, Animal; Mammary Glands, Human; Mice; Neoplasm Metastasis; Neoplasms; Prolactin
PubMed: 33109441
DOI: 10.1016/j.semcdb.2020.10.005 -
Frontiers in Endocrinology 2021Prolactin (PRL) is a hormone produced by the pituitary gland and multiple non-pituitary sites, vital in several physiological processes such as lactation, pregnancy,... (Review)
Review
Prolactin (PRL) is a hormone produced by the pituitary gland and multiple non-pituitary sites, vital in several physiological processes such as lactation, pregnancy, cell growth, and differentiation. However, PRL is nowadays known to have a strong implication in oncogenic processes, making it essential to delve into the mechanisms governing these actions. PRL and its receptor (PRLR) activate a series of effects such as survival, cellular proliferation, migration, invasion, metastasis, and resistance to treatment, being highly relevant in developing certain types of cancer. Because women produce high levels of PRL, its influence in gynecological cancers is herein reviewed. It is interesting that, other than the 23 kDa PRL, whose mechanism of action is endocrine, other variants of PRL have been observed to be produced by tumoral tissue, acting in a paracrine/autocrine manner. Because many components, including PRL, surround the microenvironment, it is interesting to understand the hormone's modulation in cancer cells. This work aims to review the most important findings regarding the PRL/PRLR axis in cervical, ovarian, and endometrial cancers and its molecular mechanisms to support carcinogenesis.
Topics: Cell Transformation, Neoplastic; Female; Genital Neoplasms, Female; Humans; Prolactin; Receptors, Prolactin; Signal Transduction; Tumor Microenvironment
PubMed: 34745013
DOI: 10.3389/fendo.2021.747810