Showing papers on "Prolactin published in 2017"
TL;DR: Correlational and experimental studies indicate that OT is associated with increased parent-child synchrony, sensitive parenting, and parental contact; interacts with other hormones, such as vasopressin, cortisol, or testosterone to create parent-specific effects; is associatedWith activation of key nodes in the parental brain, and is altered in conditions of high risk or parental psychopathology.
Abstract: In non-human mammals mothering is hormone-dependent, with crucial roles for oxytocin and prolactin. While human parenting is not hormone-dependent, hormonal changes in oxytocin, vasopressin, prolactin, testosterone, and cortisol prime and accompany the expression of parenting. In the following we focus on oxytocin (OT) as a key hormone in human parenting. OT is a nine-amino-acid neuropeptide hormone which evolved from the ancient vasotocin molecule approximately 650 MYO. OT is implicated in sociality across vertebrate evolution and substantial research has pinpointed its role in birth, lactation, and maternal care in mammals. Over the last decade, studies have begun to examine peripheral levels of OT – in plasma, saliva, urine, and to lesser extend CSF – in humans as well as OT administration to parents. Correlational and experimental studies indicate that OT is associated with increased parent-child synchrony, sensitive parenting, and parental contact; interacts with other hormones, such as vasopressin, cortisol, or testosterone to create parent-specific effects; is associated with activation of key nodes in the parental brain, and is altered in conditions of high risk or parental psychopathology. We conclude by discussing the potential role of OT in interventions for high-risk parenting.
104 citations
TL;DR: A critical role is established for prolactin-induced behavioral responses in the maternal brain, ensuring survival of mammalian offspring.
Abstract: Pregnancy hormones, such as prolactin, sensitize neural circuits controlling parental interactions to induce timely activation of maternal behaviors immediately after parturition. While the medial preoptic area (MPOA) is known to be critical for maternal behavior, the specific role of prolactin in this brain region has remained elusive. Here, we evaluated the role of prolactin action in the MPOA using complementary genetic strategies in mice. We characterized prolactin-responsive neurons within the MPOA at different hormonal stages and delineated their projections in the brain. We found that MPOA neurons expressing prolactin receptors (Prlr) form the nexus of a complex prolactin-responsive neural circuit, indicating that changing prolactin levels can act at multiple sites and thus, impinge on the overall activity of a distributed network of neurons. Conditional KO of Prlr from neuronal subpopulations expressing the neurotransmitters GABA or glutamate within this circuit markedly reduced the capacity for prolactin action both in the MPOA and throughout the network. Each of these manipulations, however, produced only subtle impacts on maternal care, suggesting that this distributed circuit is robust with respect to alterations in prolactin signaling. In contrast, acute deletion of Prlr in all MPOA neurons of adult female mice resulted in profound deficits in maternal care soon after birth. All mothers abandoned their pups, showing that prolactin action on MPOA neurons is necessary for the normal expression of postpartum maternal behavior in mice. Our data establish a critical role for prolactin-induced behavioral responses in the maternal brain, ensuring survival of mammalian offspring.
97 citations
TL;DR: The distribution and putative expression of prolactin and its receptors in several neuronal tissues suggests that this hormone has pleiotropic functions in the brain.
Abstract: Prolactin is a peptide hormone mainly synthetized and secreted by the anterior pituitary gland, but also by extrapituitary tissues, such as mammary gland, decidua, prostate, skin, and possibly the brain. Similarly, prolactin receptor is expressed in the pituitary gland, many peripheral tissues, and in contrast to prolactin, its receptor has been consistently detected in several brain regions, such as cerebral cortex, olfactory bulb, hypothalamus, hippocampus, amygdala, among others. Classically, prolactin function has been related to the stimulation of lactogenesis and galactopoiesis, however, it is well known that prolactin induces a wide range of functions in different brain areas. The aim of this review is to summarize recent reports on prolactin and prolactin receptor synthesis and localization, as well as recapitulate both the classic functions attributed to this hormone in the brain and the recently described functions such as neurogenesis, neurodevelopment, sleep, learning and memory, and neuroprotection. The distribution and putative expression of prolactin and its receptors in several neuronal tissues suggests that this hormone has pleiotropic functions in the brain.
76 citations
TL;DR: The distribution of GH-responsive cells was found primarily distributed in brain regions implicated in neurovegetative, emotional/motivational and cognitive functions and suggest that central GH signaling is likely more ample and complex than formerly recognized.
Abstract: Growth hormone (GH) exerts important biological effects primarily related to growth and metabolism. However, the role of GH signaling in the brain is still elusive. To better understand GH functions in the brain, we mapped the distribution of GH-responsive cells and identified the receptors involved in GH central effects. For this purpose, mice received an acute intraperitoneal challenge with specific ligands of the GH receptor (mouse GH), prolactin receptor (prolactin) or both receptors (human GH), and their brains were subsequently processed immunohistochemically to detect the phosphorylated form of STAT5 (pSTAT5). GH induced pSTAT5 immunoreactivity in neurons, but not in astroglial cells of numerous brain regions, including the cerebral cortex, nucleus accumbens, hippocampus, septum and amygdala. The most prominent populations of GH-responsive neurons were located in hypothalamic areas, including several preoptic divisions, and the supraoptic, paraventricular, suprachiasmatic, periventricular, arcuate, ventromedial, dorsomedial, tuberal, posterior and ventral premammillary nuclei. Interestingly, many brainstem structures also exhibited GH-responsive cells. Experiments combining immunohistochemistry for pSTAT5 and in situ hybridization for GH and prolactin receptors revealed that human GH induced pSTAT5 in most, but not all, brain regions through both prolactin and GH receptors. Additionally, males and females exhibited a similar number of GH-responsive cells in forebrain structures known to be sexually dimorphic. In summary, we found GH-responsive cells primarily distributed in brain regions implicated in neurovegetative, emotional/motivational and cognitive functions. Our findings deepen the understanding of GH signaling in the brain and suggest that central GH signaling is likely more ample and complex than formerly recognized.
66 citations
TL;DR: The hypothesis that pregnancy and lactation are sensitive to low‐dose xenoestrogen exposures is supported, as observations of nursing behavior collected during the lactational period revealed stage‐specific effects on both pup and maternal nursing behaviors.
Abstract: High doses of estrogenic pharmaceuticals were once prescribed to women to halt lactation. Yet, the effects of low-level xenoestrogens on lactation remain poorly studied. We investigated the effects of bisphenol S (BPS), an estrogen receptor (ER) agonist, on the lactating mammary gland; the arcuate nucleus, a region of the hypothalamus important for neuroendocrine control of lactational behaviors; and nursing behavior in CD-1 mice. Female mice were exposed to vehicle, 2 or 200 µg BPS/kg/d from pregnancy day 9 until lactational day (LD) 20, and tissues were collected on LD21. Tissues were also collected from a second group at LD2. BPS exposure significantly reduced the fraction of the mammary gland comprised of lobules, the milk-producing units, on LD21, but not LD2. BPS also altered expression of Esr1 and ERα in the mammary gland at LD21, consistent with early involution. In the arcuate nucleus, no changes were observed in expression of signal transducer and activator of transcription 5, a marker of prolactin signaling, or ERα, suggesting that BPS may act directly on the mammary gland. However, observations of nursing behavior collected during the lactational period revealed stage-specific effects on both pup and maternal nursing behaviors; BPS-treated dams spent significantly more time nursing later in the lactational period, and BPS-treated pups were less likely to initiate nursing. Pup growth and development were also stunted. These data indicate that low doses of BPS can alter lactational behaviors and the maternal mammary gland. Together, they support the hypothesis that pregnancy and lactation are sensitive to low-dose xenoestrogen exposures.
64 citations
TL;DR: Based on the available literature, it is clear that growth hormone plays a significant role in the development, progression, and metastasis of breast cancer by influencing tumor angiogenesis, stemness, and chemoresistance.
Abstract: Breast cancer is one of the most common cancers diagnosed in women. Approximately two-thirds of all breast cancers diagnosed are classified as hormone dependent, which indicates that hormones are the key factors that drive the growth of these breast cancers. Ovarian and pituitary hormones play a major role in the growth and development of normal mammary glands and breast cancer. In particular, the effect of the ovarian hormone estrogen has received much attention in regard to breast cancer. Pituitary hormones prolactin and growth hormone have also been associated with breast cancer. Although the role of these pituitary hormones in breast cancers has been studied, it has not been investigated extensively. In this review, we attempt to compile basic information from most of the currently available literature to understand and demonstrate the significance of growth hormone in breast cancer. Based on the available literature, it is clear that growth hormone plays a significant role in the development, progression, and metastasis of breast cancer by influencing tumor angiogenesis, stemness, and chemoresistance.
60 citations
TL;DR: Convergent findings suggest that morning cortisol is reduced in pregnant and postpartum women with MD, and definitive evidence for an association between specific hormonal fluctuations and mood disorders in the peripartum period remains elusive.
Abstract: Pregnancy and postpartum are periods of high susceptibility to major depression (MD) and other mood disorders. The peripartum period is also a time of considerable changes in the levels of hormones, including cortisol, thyroid-stimulating hormone (TSH), prolactin, gonadotropins, and gonadal steroids. To investigate the relationship between mood and hormonal changes during and after pregnancy, we reviewed published reports of hormonal measures during this time frame, searched via PubMed and Web of Science. Studies were included if women in the antepartum or postpartum periods were clinically diagnosed with MD, and if there were repeated measures of cortisol, TSH, or prolactin. For these three hormones, the numbers of human studies that met these criteria were 15, 7, and 3, respectively. Convergent findings suggest that morning cortisol is reduced in pregnant and postpartum women with MD. Evidence did not support changes in TSH as a marker of MD during the peripartum period, and evidence for changes in prolactin in peripartum MD was equivocal. Aside from reduced morning cortisol in peripartum women with MD, definitive evidence for an association between specific hormonal fluctuations and mood disorders in the peripartum period remains elusive.
56 citations
TL;DR: Clinical and experimental results leave little doubt that PRL contributes to the pathogenesis and clinical expression of SLE, and new evidence has confirmed a significant correlation between serum PRL levels and disease activity.
Abstract: Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.
50 citations
TL;DR: CPA is likely to cause a temporary increase in serum Prolactin, with prolactin levels returning to normal after orchiectomy and CPA discontinuation, according to a retrospective analysis of trans women receiving gender affirming hormones.
Abstract: Purpose: Hormone treatment in trans women in Europe usually consists of the administration of estrogens and antiandrogens, for example, cyproterone acetate (CPA). Mild serum prolactin elevations during follow-up are attributed to estrogen therapy. This analysis evaluates whether CPA contributes to the elevation of prolactin in trans women receiving gender affirming hormones. Methods: This study is part of the endocrine part of the European Network for the Investigation of Gender Incongruence (ENIGI). Belgian data were selected for this substudy. Trans women who initiated gender affirming hormone treatment and underwent orchiectomy were prospectively evaluated. Trans women were treated with oral CPA 50 mg in combination with estrogen substitution. Postsurgery, estrogen was reinitiated in an unchanged dose. Sex steroids, gonadotropins, and prolactin were compared at baseline, pre- and postsurgery in patients receiving orchiectomy, and at baseline, 12, and 18 months in patients who did not undergo o...
47 citations
TL;DR: Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones, and PACAP38 infusion elevated the plasma Levels of VIP, prolactin, S100B and TSH, but not CGRP and TNF α.
Abstract: Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65-70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 ( MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP ( p = 0.026), prolactin ( p = 0.011), S100B ( p 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant ( p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFα. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones.
47 citations
TL;DR: It seems possible that AQP1 present in Gc and Tc cells may be implicated not only in the regulation of water homeostasis required for follicle development but also in cell proliferation and migration.
Abstract: The present in vitro study analyzed whether the hormones that affect the ovarian follicular steroidogenesis process also participate in the regulation of AQP1 mRNA and protein expression. Granulosa (Gc) and theca cells (Tc) of medium and large porcine ovarian follicles were exposed to follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) for 24 h in separated cells and co-cultures of these cells. Real-time PCR, Western blotting, immunofluorescence and volumetric analysis were then performed. Gonadotropins, PRL and GH had a stimulatory impact on AQP1 mRNA and protein expression in Gc and Tc of medium and large ovarian cells. Moreover, swelling assays, in response to a hypotonic environment, demonstrated the functional presence of AQPs in porcine Gc and Tc. Immunofluorescence analysis showed that AQP1 protein was mainly localized in the perinuclear region of the cytoplasm, endosomes and cell membranes of Gc and Tc from medium and large follicles. It seems possible that AQP1 present in Gc and Tc cells may be implicated not only in the regulation of water homeostasis required for follicle development but also in cell proliferation and migration.
TL;DR: The aim is to provide a clinically useful overview on the pathophysiology and biological behaviour of this rare complication of pregnancy and to assess published research on this topic including diagnostic and therapeutic guidelines.
Abstract: Meningioma is among the most frequent brain tumours predominantly affecting elderly women. Epidemiological studies have shown that at the age of fertility the incidence is relatively low. The biological behaviour of meningioma in pregnancy is different from other meningiomas. The possible explanation is rooted in the complex physiological changes and hormonal differences during pregnancy. The increased meningioma growth observed in pregnancy is presumably the result of endocrine mechanisms. These include increase in progesterone, human placental lactogen (hPL) and prolactin (PRL) serum levels. In contrast, levels of pituitary hormones such as follicle stimulating hormone (FSH), luteinizing hormone (LH) and human chorionic gonadotropin (hCG) produced by the placenta are decreasing in the mother prior to childbirth. Besides, vascular factors also play a crucial role. Peritumoral brain edema (PTBE), with well-known causative association with vascular endothelial growth factor (VEGF), can often be seen both with imaging and in the surgical specimens. Our aim is to assess published research on this topic including diagnostic and therapeutic guidelines, and to provide a clinically useful overview on the pathophysiology and biological behaviour of this rare complication of pregnancy.
TL;DR: How the shaping of the maternal brain takes place prior to parturition is reflected and lactogenic agents are suggested to be important candidates in the development of maternal behaviours already during pregnancy.
Abstract: Prolactin is fundamental for the expression of maternal behaviour. In virgin female rats, prolactin administered upon steroid hormone priming accelerates the onset of maternal care. By contrast, the role of prolactin in mice maternal behaviour remains unclear. This study aims at characterizing central prolactin activity patterns in female mice and their variation through pregnancy and lactation. This was revealed by immunoreactivity of phosphorylated (active) signal transducer and activator of transcription 5 (pSTAT5-ir), a key molecule in the signalling cascade of prolactin receptors. We also evaluated non-hypophyseal lactogenic activity during pregnancy by administering bromocriptine, which suppresses hypophyseal prolactin release. Late-pregnant and lactating females showed significantly increased pSTAT5-ir resulting in a widespread pattern of immunostaining with minor variations between pregnant and lactating animals, which comprises nuclei of the sociosexual and maternal brain, including telencephalic (septum, nucleus of the stria terminalis, and amygdala), hypothalamic (preoptic, paraventricular, supraoptic, and ventromedial), and midbrain (periaqueductal grey) regions. During late pregnancy, this pattern was not affected by the administration of bromocriptine, suggesting it to be elicited mostly by non-hypophyseal lactogenic agents, likely placental lactogens. Virgin females displayed, instead, a variable pattern of pSTAT5-ir restricted to a subset of the brain nuclei labelled in pregnant and lactating mice. A hormonal substitution experiment confirmed that estradiol and progesterone contribute to the variability found in virgin females. Our results reflect how the shaping of the maternal brain takes place prior to parturition and suggest that lactogenic agents are important candidates in the development of maternal behaviours already during pregnancy.
TL;DR: The authors found that prolactin inhibition of oxytocin neurone activity is lost in lactation, and that some of the neurones were excited by it in lactating rats.
Abstract: Key points
During lactation, prolactin promotes milk synthesis and oxytocin stimulates milk ejection.
In virgin rats, prolactin inhibits the activity of oxytocin-secreting neurones.
We found that prolactin inhibition of oxytocin neurone activity is lost in lactation, and that some oxytocin neurones were excited by prolactin in lactating rats.
The change in prolactin regulation of oxytocin neurone activity was not associated with a change in activation of intracellular signalling pathways known to couple to prolactin receptors.
The change in prolactin regulation of oxytocin neurone activity in lactation might allow coordinated activation of both populations of neurones when required for successful lactation.
Abstract
Secretion of prolactin for milk synthesis and oxytocin for milk secretion is required for successful lactation. In virgin rats, prolactin inhibits oxytocin neurones but this effect would be counterproductive during lactation when secretion of both hormones is required for synthesis and delivery of milk to the newborn. Hence, we determined the effects of intracerebroventricular (i.c.v.) prolactin on oxytocin neurones in urethane-anaesthetised virgin, pregnant and lactating rats. Prolactin (2 μg) consistently inhibited oxytocin neurones in virgin and pregnant rats (by 1.9 ± 0.4 and 1.8 ± 0.5 spikes s−1, respectively), but not in lactating rats; indeed, prolactin excited six of 27 oxytocin neurones by >1 spike s−1 in lactating rats but excited none in virgin or pregnant rats (χ22 = 7.2, P = 0.03). Vasopressin neurones were unaffected by prolactin (2 μg) in virgin rats but were inhibited by 1.1 ± 0.2 spikes s−1 in lactating rats. Immunohistochemistry showed that i.c.v. prolactin increased oxytocin expression in virgin and lactating rats and increased signal transducer and activator of transcription 5 phosphorylation to a similar extent in oxytocin neurones of virgin and lactating rats. Western blotting showed that i.c.v. prolactin did not affect phosphorylation of extracellular regulated kinase 1 or 2, or of Akt in the supraoptic or paraventricular nuclei of virgin or lactating rats. Hence, prolactin inhibition of oxytocin neurones is lost in lactation, which might allow concurrent elevation of prolactin secretion from the pituitary gland and activation of oxytocin neurones for synthesis and delivery of milk to the newborn.
TL;DR: In FtMs, prolactin decreased consistently during CHT and in MtFs, prol actin increased during pre‐surgical CHT but normalised after gonadectomy, suggesting it is likely that CPA induces increasing Prolactin levels in FtMs and MtFs.
Abstract: Summary
The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: −33%, −12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (≥0.6 IU L−1). In the retrospective population, post-gonadectomy levels in FtMs were lower than baseline levels (−39%; 95CI: −51%, −20%) while in MtFs post-gonadectomy levels and baseline levels were comparable (−6%; 95CI: −24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs.
TL;DR: Kp-10 or its analogues could have therapeutic application as an alternative approach to restore ovarian function and fertility in women with hPRL-HA resistant to dopamine agonists and in whom pituitary surgery is not possible.
Abstract: Context Hyperprolactinemia-induced hypogonadotropic amenorrhea (hPRL-HA) is a major cause of hypothalamic gonadotrophin-releasing hormone (GnRH) deficiency in women. In hyperprolactinemic mice, we previously demonstrated that hypothalamic kisspeptin (Kp) expression was diminished and that Kp administration restored hypothalamic GnRH release, gonadotropin secretion, and ovarian cyclicity, suggesting that Kp neurons could also play a role in hPRL-HA. Objective To study the effect of Kp-10 on the gonadotropic-ovarian axis in women with hPRL-HA. Patients Two women (32 and 36 years old) with chronic hPRL-HA (prolactin: between 94 and 102 and 98 and 112 ng/mL, respectively) caused by cabergoline-resistant microprolactinomas. Interventions Cabergoline was discontinued 6 months before inclusion. Blood samples were taken every 10 minutes for 12 hours during 2 consecutive days to evaluate luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Serum estradiol (E2), testosterone (T), and inhibin B (IB) levels were also measured. Vehicle or Kp-10 (1.5 μg/kg/h) was infused intravenously for 12 hours. Results Kp-10 induced a significant increase in LH and FSH levels and increased LH pulses. E2, T, and IB serum levels were also significantly increased. Conclusions In this exploratory study, we demonstrated that administration of Kp-10 reactivated gonadotropin secretion in women with hPRL-HA and increased ovarian activity. Our data suggest that, as in rodents, GnRH deficiency in hPRL-HA is also mediated by an impairment of hypothalamic Kp secretion. Kp-10 or its analogues could have therapeutic application as an alternative approach to restore ovarian function and fertility in women with hPRL-HA resistant to dopamine agonists and in whom pituitary surgery is not possible.
TL;DR: Clinicians should be aware about the risk of hypophysitis during treatment with immune check-point inhibitors and the necessity of investigating pituitary function during therapy, as part of clinical trials or after its marketing.
Abstract: Ipilimumab is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4, that has been shown to significantly improve survival in patients with metastatic melanoma. Blocking cytotoxic T-lymphocyte antigen-4 elicits T cell activation, proliferation and anti-tumor response, but can also trigger immune-related adverse events. Among immune-related endocrinopathies, hypophysitis represents the most frequent, with an incidence up to 17% in patients treated with ipilimumab. We report nine cases of ipilimumab-induced hypophysitis in a cohort of 273 patients treated with ipilimumab between 2006 and 2015, as part of clinical trials or after its marketing. Thyroid function tests were scheduled at screening and during follow up (every 21 days) in all patients. Cortisol, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, and estradiol (for females) or testosterone (for males), prolactin, growth hormone, insulin-like growth factor 1 were measured only in case of clinical suspicion. The incidence of hypophysitis was 3.3%. The most frequent pituitary failure was adrenocorticotropic hormone and thyroid stimulating hormone secretion with a complete recovery of thyroid stimulating hormone, but not of adrenocorticotropic hormone during follow up. All patients had negative pituitary antibodies. The main symptoms at diagnosis were fatigue and headache. Clinicians should be aware about the risk of hypophysitis during treatment with immune check-point inhibitors and the necessity of investigating pituitary function during therapy. Pituitary magnetic resonance imaging does not seem pivotal for a definite diagnosis if not performed at the onset of disease.
TL;DR: End‐stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolACTin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum Prolactin have not been examined.
Abstract: Introduction End-stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined
Methods The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in-center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health-related quality of life, self-reported physical function, mental health and cognition Serum prolactin concentrations were measured at baseline and 12-month follow-up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin
Findings Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th–75th percentile 48–195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials
Discussion Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one-year period
TL;DR: Evidence is provided that prolactin secreted in response to acute stress is sufficient to activate Prolactin receptors in selected target tissues known to be involved in the physiological adaptation to stress.
Abstract: Prolactin is a pleiotropic peptide hormone produced by the lactotrophs in the anterior pituitary. Its rate of secretion is primarily regulated by a negative-feedback mechanism where prolactin stimulates the activity of the tuberoinfundibular dopaminergic (TIDA) neurones, increasing their release of dopamine, which accesses the pituitary via the median eminence to suppress further prolactin secretion. In addition to its well established role in lactation, circulating prolactin is secreted in response to stress, although the mechanism by which this is achieved or its cellular targets remains unknown. In the present study, we show that 15 minutes of restraint stress causes an approximately seven-fold increase in circulating prolactin concentration in male mice. Monitoring prolactin receptor activation, using immunohistochemistry to determine the level and distribution of tyrosine phosphorylated signal transducer and activator of transcription 5 (pSTAT5), we show that this stress-induced increase in prolactin interacts with both central and peripheral targets. Restraint stress for 15 minutes significantly increased pSTAT5 staining in the arcuate nucleus, median eminence and the zona fasciculata of the adrenal cortex. In each case, this response was prevented by pretreating the animals with bromocriptine to block prolactin secretion from the pituitary. Interestingly, in contrast to many cells in the arcuate nucleus, stress reduced pSTAT5 staining of the TIDA neurones (identified by dual-labelling for tyrosine hydroxylase). This suggests that there is reduced prolactin signalling in these cells and thus potentially a decline in their inhibitory influence on prolactin secretion. These results provide evidence that prolactin secreted in response to acute stress is sufficient to activate prolactin receptors in selected target tissues known to be involved in the physiological adaptation to stress.
TL;DR: The overall decrease in the PRL signaling pathway and consequently in target gene (lalba) mRNA transcription explain the profound negative impact of HypoT on mammary function through lactation.
TL;DR: An impaired crosstalk between the extracellular matrix and lactogenic hormone signaling pathways and epigenetic modifications of the β- Cas gene could be the molecular mechanisms by which BPA decreased β-Cas expression.
TL;DR: The findings support a possible role of prolactin in emerging psychosis and it could be speculated that stress, which can induce hyperprolactinemia, has a stronger effect on women than on men in Emerging psychosis.
TL;DR: It is concluded that prolactin is an important player in the recruitment of immune cells to the mammary gland both through its activities to increase epithelial cell number as well as production of chemo-attractants on a per cell basis.
Abstract: Immune cells in the mammary gland play a number of important roles, including protection against infection during lactation and, after passing into milk, modulation of offspring immunity. However, little is known about the mechanism of recruitment of immune cells to the lactating gland in the absence of infection. Given the importance of prolactin to other aspects of lactation, we hypothesized it would also play a role in immune cell recruitment. Prolactin treatment of adult female mice for a period equivalent to pregnancy and the first week of lactation increased immune cell flux through the mammary gland, as reflected in the number of immune cells in mammary gland-draining, but not other lymph nodes. Conditioned medium from luminal mammary epithelial HC11 cell cultures was chemo-attractive to CD4+ and CD8+ T cells, CD4+ and CD8+ memory T cells, B cells, macrophages, monocytes, eosinophils, and neutrophils. Prolactin did not act as a direct chemo-attractant, but through effects on luminal mammary epithelial cells, increased the chemo-attractant properties of conditioned medium. Macrophages and neutrophils constitute the largest proportion of cells in milk from healthy glands. Depletion of CCL2 and CXCL1 from conditioned medium reduced chemo-attraction of monocytes and neutrophils, and prolactin increased expression of these two chemokines in mammary epithelial cells. We conclude that prolactin is an important player in the recruitment of immune cells to the mammary gland both through its activities to increase epithelial cell number as well as production of chemo-attractants on a per cell basis.
TL;DR: PRL, EGF and glucocorticoids have distinct roles in the establishment of β-casein secretion pathway, which is focused on prolactin, epidermal growth factor and EGF, which increase in blood plasma and milk around parturition.
TL;DR: A significant association was established between various HTR2C polymorphisms and HPRL in a population of 446 Caucasians with a clinical diagnosis of schizophrenia who were treated with classical and/or atypical antipsychotic drugs.
Abstract: Objectives: Hyperprolactinaemia (HPRL) is a classical side effect of antipsychotic drugs primarily attributed to blockade of dopamine D2 subtype receptors in the pituitary gland. Although dopamine is considered the primary factor inhibiting prolactin release, the activity of prolactin-producing lactotrophs is also regulated by the secretagogues thyrotrophin releasing hormone, vasoactive intestinal polypeptide and serotonin (5-hydroxytryptamine; 5-HT).Methods: We describe the association between HPRL and a set of 29 SNPs from 5-HT receptor genes HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6 in a population of 446 Caucasians (221 males/225 females) with a clinical diagnosis of schizophrenia (according to ICD-10: F20) who were treated with classical and/or atypical antipsychotic drugs.Results: None of the studied autosomal markers were found to be associated with HPRL. However, a significant association was established between various HTR2C polymorphisms and HPRL.Conclusions: This study revealed ...
TL;DR: Evidence is provided that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation, and Kp seems to play a role in the peak phase of the estradiol-induced PRL surge.
Abstract: Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge.
TL;DR: Intensive training of military cadets resulted in changes of menstruation and related biomarkers, and cortisol, prolactin, and TSH level increased but levels of CRH, endorphin-&bgr;, NPY, orexin-A, ghrelin, E2 and T4 decreased throughout the training.
TL;DR: It is demonstrated that circulating prolactin levels are higher in patients with SLE, and that a significantly positive correlation exists between prolactIn levels and SLE activity.
Abstract: ObjectiveThis study aimed to evaluate the relationship between circulating prolactin level and systemic lupus erythematosus (SLE), and to establish a correlation between plasma/serum prolactin leve...
TL;DR: No significant increase of tumor size was observed in patients with controlled prolactin levels on DA, and MRI follow-up appears unnecessary in Patients with biologically controlled macroprolactinomas.
Abstract: Objective Both antitumor and antisecretory efficacies of dopamine agonists (DA) make them the first-line treatment of macroprolactinomas. However, there is no guideline for MRI follow-up once prolactin is controlled. The aim of our study was to determine whether a regular MRI follow-up was necessary in patients with long-term normal prolactin levels under DA. Patients and methods We conducted a retrospective multicenter study (Marseille, Paris La Pitie Salpetriere and Nancy, France; Liege, Belgium) including patients with macroprolactinomas (largest diameter: >10 mm and baseline prolactin level: >100 ng/mL) treated by dopamine agonists, and regularly followed (pituitary MRI and prolactin levels) during at least 48 months once normal prolactin level was obtained. Results In total, 115 patients were included (63 men and 52 women; mean age at diagnosis: 36.3 years). Mean baseline prolactin level was 2224 ± 6839 ng/mL. No significant increase of tumor volume was observed during the follow-up. Of the 21 patients (18%) who presented asymptomatic hemorrhagic changes of the macroprolactinoma on MRI, 2 had a tumor increase (2 and 7 mm in the largest size). Both were treated by cabergoline (1 mg/week) with normal prolactin levels obtained for 6 and 24 months. For both patients, no further growth was observed on MRI during follow-up at the same dose of cabergoline. Conclusion No significant increase of tumor size was observed in our patients with controlled prolactin levels on DA. MRI follow-up thus appears unnecessary in patients with biologically controlled macroprolactinomas.
TL;DR: Very recently, dopamine agonists have been demonstrated to be efficacious in the treatment of some autoimmune disorders, placing PRL-mediated interactions as potential therapeutic targets for treating autoimmunity.
Abstract: Various lines of evidence show that prolactin (PRL) is an immunomodulator in health and disease. Cells of the immune system express PRL receptors and respond to the cognate ligand. Also, PRL itself is produced by several immune cells, indicating that in addition to its classic endocrine effects, it may also act via paracrine/autocrine pathways. PRL stimulates B and T lymphocyte proliferation, and its excess is associated with the appearance or recrudescence of various systemic and organ-specific autoimmune diseases, as demonstrated by experimental studies performed in mice, and by human case reports and case control studies. Very recently, dopamine agonists have been demonstrated to be efficacious in the treatment of some autoimmune disorders, placing PRL-mediated interactions as potential therapeutic targets for treating autoimmunity.