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Neuroendocrinology 2022Prolactin (PRL) is one of the most diverse pituitary hormones and is known to modulate normal neuronal function and neurodegenerative conditions. Many studies have... (Review)
Review
BACKGROUND
Prolactin (PRL) is one of the most diverse pituitary hormones and is known to modulate normal neuronal function and neurodegenerative conditions. Many studies have described the influence that PRL has on the central nervous system and addressed its contribution to neurodegeneration, but little is known about the mechanisms responsible for the effects of PRL on neurodegenerative disorders, especially on Alzheimer's disease (AD) and Parkinson's disease (PD).
SUMMARY
We review and summarize the existing literature and current understanding of the roles of PRL on various PRL aspects of AD and PD.
KEY MESSAGES
In general, PRL is viewed as a promising molecule for the treatment of AD and PD. Modulation of PRL functions and targeting of immune mechanisms are needed to devise preventive or therapeutic strategies.
Topics: Alzheimer Disease; Humans; Neurons; Parkinson Disease; Prolactin
PubMed: 34126620
DOI: 10.1159/000517798 -
The International Journal of... Nov 2023The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between...
BACKGROUND
The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics.
METHODS
We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features.
RESULTS
At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients.
CONCLUSION
This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind.
Topics: Humans; Male; Cognition; Follow-Up Studies; Oxytocin; Prolactin; Psychotic Disorders; Homocysteine
PubMed: 37603404
DOI: 10.1093/ijnp/pyad051 -
Breast Cancer Research : BCR Mar 2023Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the prolactin receptor (PRLR) can activate the transcription...
BACKGROUND
Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the prolactin receptor (PRLR) can activate the transcription factor STAT5, thus, we examined the association between plasma prolactin and breast cancer risk by tumor expression of PRLR, STAT5, and the upstream kinase JAK2.
METHODS
Using data from 745 cases and 2454 matched controls in the Nurses' Health Study, we conducted polytomous logistic regression to examine the association between prolactin (> 11 ng/mL vs. ≤ 11 ng/mL) measured within 10 years of diagnosis and breast cancer risk by PRLR (nuclear [N], cytoplasmic [C]), phosphorylated STAT5 (pSTAT5; N, C), and phosphorylated JAK2 (pJAK2; C) tumor expression. Analyses were conducted separately in premenopausal (n = 168 cases, 765 controls) and postmenopausal women (n = 577 cases, 1689 controls).
RESULTS
In premenopausal women, prolactin levels > 11 ng/mL were positively associated with risk of tumors positive for pSTAT5-N (OR 2.30, 95% CI 1.02-5.22) and pSTAT5-C (OR 1.64, 95% CI 1.01-2.65), but not tumors that were negative for these markers (OR 0.98, 95% CI 0.65-1.46 and OR 0.73, 95% CI 0.43-1.25; p-heterogeneity = 0.06 and 0.02, respectively). This was stronger when tumors were positive for both pSTAT5-N and pSTAT5-C (OR 2.88, 95% CI 1.14-7.25). No association was observed for PRLR or pJAK2 (positive or negative) and breast cancer risk among premenopausal women. Among postmenopausal women, plasma prolactin levels were positively associated with breast cancer risk irrespective of PRLR, pSTAT5, or pJAK2 expression (all p-heterogeneity ≥ 0.21).
CONCLUSION
We did not observe clear differences in the association between plasma prolactin and breast cancer risk by tumor expression of PRLR or pJAK2, although associations for premenopausal women were observed for pSTAT5 positive tumors only. While additional studies are needed, this suggests that prolactin may act on human breast tumor development through alternative pathways.
Topics: Female; Humans; Breast Neoplasms; Prolactin; STAT5 Transcription Factor
PubMed: 36882838
DOI: 10.1186/s13058-023-01618-3 -
Biological Research For Nursing Jan 2022Postpartum fatigue is a common disorder worldwide and affects both physical and mental functioning. In breastfeeding women, Prolactin (PRL) is not only involved in...
Postpartum fatigue is a common disorder worldwide and affects both physical and mental functioning. In breastfeeding women, Prolactin (PRL) is not only involved in immunoregulation, but also responsible for lactation. Prolactin levels in women with chronic fatigue are higher than normal, but a chronic fatigue state inhibits postpartum lactation in humans. This paper explored the inhibition mechanism of lactation by postpartum fatigue in rats. Postpartum fatigue models were built by forcing mother rats to stand in water and divided into 3-hour, 9-hour and 15-hour per day fatigue groups according to the underwater time. Mother rats and their offspring were reunited in a dry cage for 90 minutes every 3 hours for feeding. The expression of PRL, PRL receptor (PRLR), Janus Kinase 2 (JAK 2), and Signal transducers and activators of transcription 5 (STAT5) mRNA were analyzed and the microstructure of mammary gland were observed under light and electron microscopy. The expression of pituitary PRL mRNA and its downstream signaling pathway JAK2 and STAT5 mRNA were down-regulated in the severe postpartum fatigue rats. PRL mRNA responses were dose-related to duration of fatigue. The expression of PRLR mRNA increased. Postpartum fatigue led to functional degeneration of mammary gland. The breast lobules were shrunk and the number of alveoli were decreased. Few milk protein granules and fat droplets were observed in the cytoplasm under transmission electron microscope. Postpartum fatigue inhibits the lactation by down-regulating the expression of PRL and PRL-dependent signaling pathway in rats.
Topics: Animals; Breast Feeding; Fatigue; Female; Humans; Lactation; Mammary Glands, Animal; Postpartum Period; Prolactin; RNA, Messenger; Rats; STAT5 Transcription Factor
PubMed: 34719282
DOI: 10.1177/10998004211050047 -
Journal of Translational Medicine Jul 2023Despite advances in pharmacology, the treatment of schizophrenia (SZ) remains a challenge due to relapse after antipsychotic discontinuation and multiple adverse effects... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Despite advances in pharmacology, the treatment of schizophrenia (SZ) remains a challenge due to relapse after antipsychotic discontinuation and multiple adverse effects of antipsychotics. We hypothesized that a low dose of risperidone in combination with sertraline would reduce serious adverse effects without decreasing treatment response. This study aimed to examine the efficacy, safety, and tolerability of low-dose risperidone combined with sertraline to reduce risperidone dose and serious adverse effects in first-episode and medication-naive (FEMN) SZ patients.
METHODS
A total of 230 patients with FEMN SZ were randomly assigned to receive low-dose risperidone in combination with sertraline (RS group) or regular-dose risperidone (control group). The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD), and Personal and Social Performance Scale (PSP) were assessed at baseline and the end of the first, second, third, and sixth months. In addition, serum prolactin levels and extrapyramidal symptoms were measured at baseline and follow-up.
RESULTS
Repeated measures ANCOVA showed significant interaction effects of treatment by time on psychotic symptoms, as well as HAMD, PSP scores, prolactin levels, and extrapyramidal symptoms (all p < 0.05). Compared with the control group, the RS group had greater decreases in PANSS total score and its subscores and HAMD score (all p < 0.01) and a greater increase in PSP total score (p < 0.01). Notably, side effects were lower in the RS group relative to the control group. Improvements in HAMD and PANSS total scores, changes in prolactin levels and gender predicted improvements in PSP from baseline to month 6.
CONCLUSIONS
Our study suggests that low-dose risperidone in combination with sertraline was more effective for psychotic symptoms and psychosocial functioning, with significantly fewer adverse effects in patients with FEMN SZ.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov, NCT04076371.
Topics: Humans; Risperidone; Schizophrenia; Sertraline; Prolactin; Antipsychotic Agents; Drug-Related Side Effects and Adverse Reactions; Treatment Outcome
PubMed: 37403159
DOI: 10.1186/s12967-023-04272-7 -
International Journal of Molecular... Feb 2024Prolactin (PRL) is a pleiotropic hormone released from lactotrophic cells of the anterior pituitary gland that also originates from extrapituitary sources and plays an... (Review)
Review
Prolactin (PRL) is a pleiotropic hormone released from lactotrophic cells of the anterior pituitary gland that also originates from extrapituitary sources and plays an important role in regulating lactation in mammals, as well as other actions. Acting in an endocrine and paracrine/autocrine manner, PRL regulates the hypothalamic-pituitary-ovarian axis, thus influencing the maturation of ovarian follicles and ovulation. This review provides a detailed discussion of the current knowledge on the role of PRL in the context of ovulation and ovulatory disorders, particularly with regard to hyperprolactinemia, which is one of the most common causes of infertility in women. Much attention has been given to the PRL structure and the PRL receptor (PRLR), as well as the diverse functions of PRLR signaling under normal and pathological conditions. The hormonal regulation of the menstrual cycle in connection with folliculogenesis and ovulation, as well as the current classifications of ovulation disorders, are also described. Finally, the state of knowledge regarding the importance of TIDA (tuberoinfundibular dopamine), KNDγ (kisspeptin/neurokinin B/dynorphin), and GnRH (gonadotropin-releasing hormone) neurons in PRL- and kisspeptin (KP)-dependent regulation of the hypothalamic-pituitary-gonadal (HPG) axis in women is reviewed. Based on this review, a rationale for influencing PRL signaling pathways in therapeutic activities accompanying ovulation disorders is presented.
Topics: Animals; Female; Humans; Kisspeptins; Mammals; Ovulation; Pituitary Gland, Anterior; Prolactin; Receptors, Prolactin
PubMed: 38396659
DOI: 10.3390/ijms25041976 -
Cephalalgia : An International Journal... Feb 2023To systemically review clinical studies investigating the role of prolactin and its receptors in headache and migraine. (Review)
Review
OBJECTIVE
To systemically review clinical studies investigating the role of prolactin and its receptors in headache and migraine.
BACKGROUND
Migraine prevalence is more common in women compared to men. As prolactin is a crucial regulator of the hypothalamus-pituitary-gonadal axis, prolactin and its receptors might contribute to signaling mechanisms underlying migraine.
METHODS
In this systematic review, we searched PubMed and EMBASE with the terms: prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain and trigeminal pain pathway for clinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.
RESULTS
Nineteen clinical studies met the inclusion criteria and were included in the qualitative and quantitative analysis. The main findings were that serum prolactin levels were found to be higher in individuals with migraine compared to healthy controls, and prolactinomas (prolactin-secreting pituitary adenomas) were correlated with higher incidence of headache in otherwise healthy individuals and migraine attacks in individuals with migraine.
CONCLUSION
Considerable evidence suggests a key role of prolactin and its receptors in migraine pathophysiology. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify influences of prolactin in migraine attack initiation.
Topics: Male; Humans; Female; Prolactin; Headache; Prolactinoma; Migraine Disorders; Hyperprolactinemia; Pituitary Neoplasms
PubMed: 36718026
DOI: 10.1177/03331024221136286 -
Headache May 2023To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology. (Review)
Review
OBJECTIVE
To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology.
BACKGROUND
The features of migraine attacks, including characteristics, duration, frequency, and prevalence, are sex-dependent with variability across a lifetime, indicating the involvement of the hypothalamus-pituitary-gonadal axis. Prolactin is a key regulator of this axis, and a new line of evidence implicates prolactin signaling in sex-related differences in pain perception.
METHODS
In this systematic review, we searched PubMed and EMBASE for the terms prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain, and trigeminal pain pathway to find preclinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.
RESULTS
Of a total of 15 preclinical articles selected, 11 were both ex vivo and in vivo, 3 were ex vivo, and 1 was an in vivo study. The main findings were that prolactin receptors are distributed in the trigeminal pain pathway, and prolactin induced migraine-like behavior in rodents. Moreover, prolactin signaling has a crucial role in calcitonin gene-related peptide (CGRP) release, a key molecule in migraine pathogenesis, and prolactin gene deletion attenuated CGRP-induced migraine-like behavior.
CONCLUSION
Preclinical data indicate a key role of prolactin and its receptors in mechanisms causing migraine. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify the influences of prolactin in migraine-attack initiation.
Topics: Humans; Calcitonin Gene-Related Peptide; Headache; Migraine Disorders; Pain; Prolactin; Animals; Mice; Rats
PubMed: 36752584
DOI: 10.1111/head.14412 -
Frontiers in Immunology 2023The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment... (Review)
Review
The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.
Topics: Pregnancy; Female; Humans; Prolactin; Decidua; Placenta; Extraembryonic Membranes; Amniotic Fluid
PubMed: 37359537
DOI: 10.3389/fimmu.2023.1212736 -
Journal of Neuroendocrinology Nov 2020Prolactin is named after its vital role of promoting milk production during lactation, although it has been implicated in multiple functions within the body, including... (Review)
Review
Prolactin is named after its vital role of promoting milk production during lactation, although it has been implicated in multiple functions within the body, including metabolism and energy homeostasis. Prolactin has been hypothesised to play a key role in driving many of the adaptations of the maternal body to allow the mother to meet the physiological demands of both pregnancy and lactation, including the high energetic demands of the growing foetus followed by milk production to support the offspring after birth. Prolactin receptors are found in many tissues involved in metabolism and food intake, such as the pancreas, liver, hypothalamus, small intestine and adipose tissue. We review the literature examining the effects of prolactin in these various tissues and how they relate to changes in function in physiological states of high prolactin, such as pregnancy and lactation, and in pathological states of hyperprolactinaemia in the adult. In many cases, whether prolactin promotes healthy metabolism or leads to dysregulation of metabolic functions is highly dependent on the situation. Overall, although prolactin may not play a major role in regulating metabolism and body weight outside of pregnancy and lactation, it definitely has the ability to contribute to metabolic function.
Topics: Animals; Female; Humans; Lactation; Metabolism; Pregnancy; Prolactin; Receptors, Prolactin
PubMed: 33463813
DOI: 10.1111/jne.12888