Prolactin In Humans Research Articles

Comparative Study of Lactogenic Effect and Milk Mutritional Density of Oral Galactagogues in Female Rabbit.

Hypogalactia and agalactia in lactating mothers are the major causes of child malnutrition, mortality, morbidity, and overall ill health. The development of such treatments requires a well-designed preclinical study with suitable laboratory animals, which needs to be improved. Thus, a suitably designed study with a laboratory animal to analyse galactagogue activity, along with an assessment of the quality and quantity of milk, is required. This study aimed to evaluate the potential of rabbits as an animal model for studying lactogenic activity. The structural homology of prolactin, prolactin, and prolactin in humans, rabbits, and rats was studied using BLAST and PyMol to assess similarity in the lactogenic system. Daily and cumulative milk production and pre-treatment (control) and post-treatment (three drugs) in rabbits were recorded and evaluated by analysing protein, fat, lactose, solid non-fat, and ash values. All parameters were recorded on the 0th day and at the end of weeks 1, 2, and 3. Mammary gland histopathology was performed to evaluate the effects on mammary glands. Homology studies revealed that the sequences of the human and rabbit prolactin genes, receptors, and hormones had a high similarity index. Treatment with Domperidone, Metoclopramide, and Shatavari significantly enhanced milk production by enhancing prolactin secretion; only Shatavari increased milk nutrition. Enlargement of the tubuloalveolar ducts of the mammary glands was observed. Our findings suggest that rabbits are robust, reproducible, ethically superior, and preclinically relevant animals for assessing lactogenic activity.

New insights of prolactin in humans: the role of nurses

Prolactin is synthesize by the anterior pituitary gland, by extrapituitary tissues, such as the mammary gland, prostate, skin and brain. It has been relateding to lactogenesis, however, it is known to induce a wide range of functions in different tissues, modulating neurogenesis, neurodevelopment, sleep, learning, memory and homeostasis of the immune system, and may be linked to different types of cancers. The objective was to identify the new insights of the prolactinemia as a biomarker or inducer of pathological processes. During lactation, prolactin promotes milk synthesis and oxytocin stimulates ejection, its increase may come from mechanisms such as nipple sucking stimulus, stress, sexual activity, protein intake, unregulated menstrual cycle and pregnancy, pharmacological or pathological origins. Prostate and breast cancers can be treated using methods to antagonize the PRL receptor and its signaling pathways, which include small molecule-based antagonists of proteins. Drugs to lower the plasma concentration of prolactin are strong candidates to be test in reuse clinical trials to improve the cognitive skills of patients with mood disorder and schizophrenia. Keeping up to date on research, in addition to seeking to evaluate all the variables and biomarkers available for the case, can increase the chance of making an early diagnosis.

Ingestion of caffeine links dopamine and 5-hydroxytryptamine release during half immersion in 42°C hot water in a humans.

The aim of this study was to investigate the serum serotonin, prolactin, and plasma dopamine levels in humans with and without caffeine ingestion during and after passive heat loading (half immersion in 42°C hot water). Thirty male volunteers participated in the randomized experiment (control group, n=15 vs. caffeine ingestion group, n=15, 3 mg/kg). After 60 min, passive heat loading was conducted for 30 min. Blood samples were collected and assessed for serum serotonin, dopamine and prolactin with and without caffeine during and after passive heat loading. Serum serotonin was significantly lower in the caffeine ingestion group compared to the control group after passive heat loading for 30 min (Post) (P<0.05) and also after 60 min of resting (P<0.01). Dopamine and prolactin were significantly higher in the caffeine ingestion group than in the control group at the Post time point (P<0.001). In conclusion, 3-mg/kg caffeine ingestion prior to passive heat loading can alter central serotonergic and dopaminergic activity, which may contribute to reduced central fatigue and subsequently, to reduced general fatigue. Prolactin responses during passive heat loading were also significantly related to caffeine ingestion in this study. However, the inhibitory effects of dopamine on prolactin by caffeine remain to be elucidated.

Prolactin Promotes Adipose Tissue Fitness and Insulin Sensitivity in Obese Males.

Excessive accumulation of body fat triggers insulin resistance and features of the metabolic syndrome. Recently, evidence has accumulated that obesity, type 2 diabetes, and metabolic syndrome are associated with reduced levels of serum prolactin (PRL) in humans and rodents, raising the question of whether low PRL levels contribute to metabolic dysfunction. Here, we have addressed this question by investigating the role of PRL in insulin sensitivity and adipose tissue fitness in obese rodents and humans. In diet-induced obese rats, treatment with PRL delivered via osmotic mini-pumps, improved insulin sensitivity, prevented adipocyte hypertrophy, and reduced inflammatory cytokine expression in visceral fat. PRL also induced increased expression of Pparg and Xbp1s in visceral adipose tissue and elevated circulating adiponectin levels. Conversely, PRL receptor null mice challenged with a high-fat diet developed greater insulin resistance, glucose intolerance, and increased adipocyte hypertrophy compared with wild-type mice. In humans, serum PRL values correlated positively with systemic adiponectin levels and were reduced in insulin-resistant patients. Furthermore, PRL circulating levels and PRL produced by adipose tissue correlated directly with the expression of PPARG, ADIPOQ, and GLUT4 in human visceral and sc adipose tissue. Thus, PRL, acting through its cognate receptors, promotes healthy adipose tissue function and systemic insulin sensitivity. Increasing the levels of PRL in the circulation may have therapeutic potential against obesity-induced metabolic diseases.

The influence of chronic and subacute exposure to lead on the levels of prolactin, leptin, osteopontin, and follistatin in humans.

This study was designed to determine the levels of prolactin, leptin, osteopontin, and follistatin in workers chronically and subacutely exposed to lead compounds. The examined population consisted of three groups. The first group was composed of 56 male workers who were chronically exposed to lead for 13.38 ± 10.38 years. The second group served as a control group and consisted of 24 male administrative workers, while the third group included 32 male workers exposed to lead for 40 ± 3 days. The levels of leptin, osteopontin, and prolactin were significantly lower in the group of workers chronically exposed to lead than in the control group by 42%, 26%, and 41%, respectively. The levels of follistatin did not differ between those groups. The levels of all measured hormones did not change after a short-term exposure to lead compared to baseline. Chronic lead exposure is associated with significantly decreased level of prolactin, leptin, and osteopontin. Lead-induced changes in the levels of these hormones may disturb many functions of the human body, including the immune response, metabolism, reproduction, and bone turnover.

Prolactin and pregnancy in mice and humans

Prolactin and pregnancy in mice and humans

Caffeine links dopamine and serotonin release during passive heat loading

Caffeine links dopamine and serotonin release during passive heat loading

A positive feedback loop between prolactin and STAT5 promotes angiogenesis.

The signal transduction events that orchestrate cellular activities required for angiogenesis remain incompletely understood. We and others recently described that proangiogenic mediators such as fibroblast growth factors can activate members of the signal transducers and activators of transcription (STAT) family. STAT5 activation is necessary and sufficient to induce migration, invasion and tube formation of endothelial cells. STAT5 effects on endothelial cells require the secretion of the prolactin (PRL) family member proliferin-1 (PLF1) in mice and PRL in humans. In human endothelial cells, PRL activates the PRL receptor (PRLR) resulting in MAPK and STAT5 activation, thus closing a positive feedback loop. In vivo, endothelial cell-derived PRL is expected to combine with PRL of tumor cell and pituitary origin to raise the concentration of this polypeptide hormone in the tumor microenvironment. Thus, PRL may stimulate tumor angiogenesis via autocrine, paracrine, and endocrine pathways. The disruption of tumor angiogenesis by interfering with PRL signaling may offer an attractive target for therapeutic intervention.

Utilizing the hair follicle to dissect the regulation and autocrine/paracrine activities of prolactin in humans

to the editor: Ferraris et al. ([4][1]) have recently reported an increase in anterior pituitary cell proliferation in Δ1-9-G129R-hPRL (competitive prolactin receptor antagonist) -expressing transgenic mice compared to wild-type controls. In addition, they reported increased proliferation/decreased

Influences of Exercise and Training on the Circulating Concentration of Prolactin in Humans

Physical activity has an impact on several endocrine functions. During exercise, certain endocrine adjustments are required to maintain the homeostasis. It is well known that, depending on the intensity and duration, exercise stimulates the release of the hormone prolactin (PRL). After the cessation of acute exercise, this effect persist and continues during the recovery period. Chronic exercise can affect the PRL basal concentration and/or the PRL response to acute exercise. The main functions of PRL are associated with the maintenance of homeostasis and processes of reproduction. A role for PRL also has been recognised as an important regulator of cellular proliferation. The present review examines the exercise-induced acute or adaptive responses of PRL secretion. It is also hypothesised that increased concentrations of PRL during exercise could play an important role for neuroplasticity as a result of involvement of the hormone in the neurogenesis in subventricular zone of the adult brain.

CATALYTIC RECEPTORS

CATALYTIC RECEPTORS

A possible relationship between prolactin and spermatogenesis in humans.

In order to investigate the effect of prolactin on spermatogenesis, we studied 205 consecutive male patients in whom 121 were normozoospermic (counts greater than 20 x 10(6)/ml), 62 were oligozoospermic (counts less than 20 x 10(6)/ml), and 22 were azoospermic. We compared prolactin with semen analysis. There was an increased incidence of high prolactin levels in the oligozoospermic and azoospermic group of patients. We noted an increase in the number of morphologically normal spermatozoa within the hyperprolactinaemic groups of patients. This may suggest that prolactin plays a regulatory role in spermatogenesis.

The effects of cannabinoids on serum cortisol and prolactin in humans

Cannabis is one of the most widely used illicit substances, and there is growing interest in the therapeutic applications of cannabinoids. While known to modulate neuroendocrine function, the precise acute and chronic dose-related effects of cannabinoids in humans are not well-known. Furthermore, the existing literature on the neuroendocrine effects of cannabinoids is limited by small sample sizes (n = 6-22), heterogeneous samples with regard to cannabis exposure (lumping users and nonusers), lack of controlling for chronic cannabis exposure, differing methodologies, and limited dose-response data. Delta-9-tetrahydrocannabinol (Delta-9-THC) was hypothesized to produce dose-related increases in plasma cortisol levels and decreases in plasma prolactin levels. Furthermore, relative to controls, frequent users of cannabis were hypothesized to show altered baseline levels of these hormones and blunted Delta-9-THC-induced changes of these hormones. Pooled data from a series of laboratory studies with multiple doses of intravenous Delta-9-THC in healthy control subjects (n = 36) and frequent users of cannabis (n = 40) was examined to characterize the acute, chronic, and acute on chronic effects of cannabinoids on plasma cortisol and prolactin levels. Hormone levels were measured before (baseline) and 70 min after administration of each dose of Delta-9-THC. Data were analyzed using linear mixed models with +70 min hormonal levels as the dependant variable and baseline hormonal level as the covariate. At socially relevant doses, Delta-9-THC raised plasma cortisol levels in a dose-dependent manner but frequent users showed blunted increases relative to healthy controls. Frequent users also had lower baseline plasma prolactin levels relative to healthy controls. These group differences may be related to the development of tolerance to the neuroendocrine effects of cannabinoids. Alternatively, these results may reflect inherent differences in neuroendocrine function in frequent users of cannabis and not a consequence of cannabis use.

Adverse effects of prolactin in rodents and humans: breast and prostate cancer

Drugs and chemicals shown to induce mammary carcinogenesis in the rat/rodent via prolactin excess have traditionally been argued to pose little or no risk to humans in a regulatory toxicology context. The basis for this assumption is reviewed and placed into context with new evidence in humans that prolactin may be a tumour promoter in the breast and prostate. This evidence includes epidemiology, patient studies involving endocrine evaluation and molecular biology in human cells. It is concluded that hyperprolactinaemia is associated with an increase in breast cancer risk in both post and premenopausal women, that rat carcinogenicity studies are predictive of the human response, and that in a regulatory toxicology context prolactin-induced mammary tumours from nongenotoxic drugs and chemicals are an adverse effect that should not be ignored. More evidence is required concerning prostate cancer risk but molecular biology indicates that prolactin also induces prostate cell proliferation and inhibits apoptosis, which are similar to the responses observed in breast cancer cells.

What Can We Learn from Rodents about Prolactin in Humans?

Prolactin (PRL) is a 23-kDa protein hormone that binds to a single-span membrane receptor, a member of the cytokine receptor superfamily, and exerts its action via several interacting signaling pathways. PRL is a multifunctional hormone that affects multiple reproductive and metabolic functions and is also involved in tumorigenicity. In addition to being a classical pituitary hormone, PRL in humans is produced by many tissues throughout the body where it acts as a cytokine. The objective of this review is to compare and contrast multiple aspects of PRL, from structure to regulation, and from physiology to pathology in rats, mice, and humans. At each juncture, questions are raised whether, or to what extent, data from rodents are relevant to PRL homeostasis in humans. Most current knowledge on PRL has been obtained from studies with rats and, more recently, from the use of transgenic mice. Although this information is indispensable for understanding PRL in human health and disease, there is sufficient disparity in the control of the production, distribution, and physiological functions of PRL among these species to warrant careful and judicial extrapolation to humans.

Prolactin expression is induced in Jurkat T-cells by β-catenin LEF-1, AP-1 and cAMP

Prolactin (PRL) in humans is produced in the pituitary as well as in extra-pituitary sites. A proximal promoter that requires the Pit-1 transcription factor controls pituitary PRL expression, whereas a distal (upstream) promoter located at 5.8kb upstream of the pituitary start site regulates extra-pituitary PRL synthesis. We have previously reported that cAMP regulates PRL transcription in Jurkat lymphocytes in part through a cAMP responsive element. Here we demonstrate that additional PRL regulatory elements corresponding to LEF-l and AP-1 transcription factor binding sites appear important for PRL expression, since factor binding by EMSA and reporter gene expression are reduced when these sites are deleted or mutated. Interestingly, over-expression of a constitutively active form of β-catenin increases PRL expression of Jurkat cells. This effect occurs through both LEF-dependent and -independent pathways. Our studies identify the distal PRL promoter as a target for β-catenin, and reveal novel pathways regulating extra-pituitary PRL expression.

Nocturnal ghrelin, ACTH, GH and cortisol secretion after sleep deprivation in humans

Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor. It is hypothesised to play a key role in energy balance stimulating food intake and body weight. Besides GH-releasing hormone (GHRH) and somatostatin, it is thought to be a regulating factor of GH release. Ghrelin also appears to be involved in sleep regulation. We showed recently that ghrelin promotes slow-wave sleep and the nocturnal release of GH, cortisol and prolactin in humans. Similarly, promotion of non-rapid-eye-movement (NREM) sleep was reported in mice after systemic ghrelin. If ghrelin is a factor that induces and/or maintains sleep, it should be enhanced after a period of sleep deprivation (SD). To clarify this issue, nocturnal ghrelin, GH, ACTH and cortisol plasma concentrations were determined and simultaneously sleep electroencephalogram (EEG) was recorded (2300-0700 h) during sleep before and after 1 night of total SD in 8 healthy subjects. Compared to baseline, ghrelin levels increased earlier by a non-significant trend, already before the beginning of recovery sleep. Further a non-significant trend occurred, suggesting higher ghrelin secretion in the first half of the night. The ghrelin maximum was found significantly earlier after SD than at baseline. GH secretion during the first half of the night and total night after SD were elevated. ACTH and cortisol were also elevated, which was most pronounced during the second half of the night. No effects of SD on the time of the maximum were found for GH, ACTH and cortisol. The increase in ACTH after SD is a novel finding. Whereas the effects of SD on ghrelin levels were relatively weak, our findings are in line with the hypothesis that ghrelin is a sleep-promoting factor in humans. Ghrelin may be involved in sleep promotion after SD.

Induction of prolactin expression and release in human preadipocytes by cAMP activating ligands

In addition to the pituitary, prolactin (PRL) in humans is produced at non-pituitary sites where it acts as a cytokine. We previously reported that PRL is expressed and released from breast adipose explants, raising the question as to the dynamics of its production and its regulation. Preadipocytes were isolated from breast adipose tissue obtained during breast reduction. PRL expression was transiently increased during early preadipocyte differentiation. Both isoproterenol, a β-adrenergic receptor agonist, and PACAP, pituitary adenylate cyclase activating peptide, increased PRL expression, and release from preadipocytes. This stimulation was suppressed by several protein kinase inhibitors, suggesting involvement of multiple signaling pathways. Transfection of preadipocytes with a superdistal PRL promoter/luciferase reporter revealed two stimulatory domains and an inhibitory domain. These data establish the transcriptional regulation of adipocyte PRL by the superdistal PRL promoter, its transient expression during adipogenesis, and the stimulatory effect of catecholamines and PACAP.

Ghrelin Has Partial or No Effect on Appetite, Growth Hormone, Prolactin, and Cortisol Release in Patients with Anorexia Nervosa

Anorexia nervosa (AN) is an eating disorder characterized by self-induced starvation. Gastric hormone ghrelin, potent orexigen, and natural GH secretagogue are increased in AN. Although exogenous ghrelin stimulates appetite, GH, prolactin, and cortisol release in humans, its effects have not been studied, during infusions, in AN patients. The objective of the study was to determine the effects of ghrelin on appetite, sleepiness, and neuroendocrine responses in AN patients. This was an acute interventional study. The study was based at a hospital. Investigated Twenty-five young women, including nine patients diagnosed with AN with very low body weight, six AN patients who partially recovered their body weight but were still amenorrheic, and 10 constitutionally thin female subjects, without history of eating disorder, weight loss, with regular menstrual cycles, were included in the study. Each patient received 300-min iv infusion of ghrelin 5 pmol/kg.min and was asked to complete Visual Analog Scale questionnaires hourly. Visual Analog Scale scores for appetite and sleepiness, GH, prolactin, and cortisol responses were measured. At baseline, AN patients had significantly higher ghrelin, GH, and cortisol levels and significantly lower leptin than constitutionally thin subjects. GH responses to ghrelin infusion were blunted in patients with AN. Ghrelin administration did not significantly affect appetite but tended to increase sleepiness in AN patients. Ghrelin is unlikely to be effective as a single appetite stimulatory treatment for patients with AN. Our results suggest that AN patients are less sensitive to ghrelin in terms of GH response and appetite than healthy controls. Ghrelin effects on sleep need further studies.

Effects of sleep deprivation on ghrelin, ACTH, GH and cortisol secretion in normal controls

Ghrelin is an endogenous ligand of the growth hormone (GH) secretagogue (GHS) receptor. Besides GH-releasing hormone (GHRH) and somatostatin it is thought to be a regulating factor of GH release. Ghrelin appears to be involved in sleep regulation. We showed recently that ghrelin promotes slow wave sleep and the nocturnal release of GH, cortisol and prolactin in humans. Similarly promotion of non-REM-sleep was reported in mice after systemic ghrelin. There are no data available about the pattern of ghrelin secretion during the recovery night after total sleep deprivation (TSD). Nocturnal ghrelin, GH, ACTH and cortisol plasma concentrations were determined by radioimmunoassay and simultaneously sleep EEG was recorded (23:00–07:00) during sleep before and after one night of TSD in 8 healthy subjects (3 females and 5 males, mean age 26.3yrs, SD 4.4). We observed a trend suggesting higher ghrelin secretion during the first half of the night after TSD (before TSD mean 466ng/ml, SD 113ng/ml, after TSD mean 545ng/ml, SD 176, p=0.093). In the night before TSD the maximum time of ghrelin secretion occured at 03:40 (SD 117min.) and after TSD this time point was 00:42 (SD 76min.), indicating an earlier ghrelin secretion after TSD (p<0.05). GH secretion during the first half of the night and total night after TSD were elevated. ACTH and cortisol were also elevated, which was most pronounced during the second half of the night (ACTH: AUC before TSD, mean 5278, SD 1814, after TSD mean 10817, SD 3314, p<0.05).