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I found this article in another forum..everyday we hear about new cause of baldness and this reason is new at least for me...
Prolactin is Fing us all over*
Prolactin wants you dead.*
Prolactin rises when you masturbate.*
Prolactin kills your hair.*
Prolactin increases your hairs sensitivity to DHT.*
A neutralizing prolactin receptor antibody whose in vivo application mimics the phenotype of female prolactin receptor-deficient mice*
Adult stem/progenitor cells are found in many tissues, where their primary role is to maintain homeostasis. Recent studies have evaluated the regulation of adult stem/progenitor cells by prolactin in various target tissues or cell types, including the mammary gland, the prostate, the brain, the bone marrow, the hair follicle, and colon cancer cells. Depending on the tissue, prolactin can either maintain stem cell quiescence or, in contrast, promote stem/progenitor cell expansion and push their progeny towards differentiation. In many instances, whether these effects are direct or involve paracrine regulators remains debated. This minireview aims to overview the current knowledge in the field.*
Transgenic Mice Overexpressing the Prolactin Gene Develop Dramatic Enlargement of the Prostate Gland*
Abstract*
An altered endocrine status of elderly men has been hypothesized to be important for development of prostate hyperplasia. The present study addresses the question whether increased PRL expression is of importance for development of prostate hyperplasia in mice. Three lines of PRL transgenic mice were generated having serum levels of PRL of approximately 15 ng/ml, 100 ng/ml, and 250 ng/ml, respectively. These mice developed dramatic enlargement of the prostate gland, approximately 20 times the normal prostate weight and they had a 4- to 5-fold increased DNA content. Histologically, the prostate glands in the transgenic mice were distended from secretion, and the amount of interstitial tissue was increased. The levels of testosterone and IGF-I were increased in the PRL transgenic animals. In mice overexpressing the bovine GH gene, displaying elevated IGF-1 levels, the prostate gland was slightly larger compared with normal mice, indicating that the effect of PRL was not primarily mediated through elevated plasma IGF-I levels. The present study suggests that PRL is an important factor in the development of prostate hyperplasia acting directly on the prostate gland or via increased plasma levels of testosterone.*
Affiliations*
Department of Physiology, Research Centre for Endocrinology and Metabolism, Göteborg University, Medicinaregatan 1F, S-413 90 Göteborg, Sweden (H.W., J.K., J.T.) and Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Sahlgrenska Hospital, S-413 45 Göteborg, Sweden (O.G.P.I.)*
Male pattern baldness in relation to prostate cancer-specific mortality: A prospective analysis in the NHANES I Epidemiologic Followup Study (NHEFS)*
Cindy Ke Zhou1, Paul H. Levine2, Sean D. Cleary2, Heather J. Hoffman2, Barry I. Graubard1, and Michael B. Cook1*
+ Author Affiliations*
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD;*
2Department of Epidemiology and Biostatistics, George Washington University, Washington, DC.*
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA*
Abstract*
Background: Androgenic action underlies prostate gland development and prostate cancer progression. However, the role of such in prostate carcinogenesis remains unclear. Results from studies that have quantitated pre-diagnostic, circulating androgens at a single time-point in relation to prostate cancer are inconsistent, possibly due to the failure to capture cumulative or relevant age-specific hormone exposure. Therefore, we used male pattern baldness as a proxy of long-term androgen exposure, and investigated the association between dermatologist-assessed male pattern baldness and prostate cancer-specific mortality in the NHANES-I Epidemiologic Followup Study (NHEFS).*
Methods: We included 4,316 men from NHEFS, who were 25-74 years, received dermatologic exams, and had no prior cancer diagnosis at baseline. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazards regression with age as the time-metric and baseline hazard stratified by age at baseline. A hybrid model was used to account for stratification and clustering of the survey design, while adjusting for variables used to calculate sample weights.*
Results: During follow-up (median = 21 years), 3,284 deaths occurred, 107 of which had the underlying cause of prostate cancer. Any degree of baldness was associated with a 56% increased risk of prostate cancer-specific mortality (HR = 1.56; 95%CI = 1.02, 2.37) and, specifically, moderate balding was associated with an 83% increased risk of the outcome (HR = 1.83; 95%CI = 1.15, 2.92), each compared with no balding. Conversely, male pattern baldness was not statistically significantly associated with all-cause mortality.*
Conclusion: Our analysis suggests that male pattern baldness is associated with an increased risk of fatal prostate cancer, and supports the hypothesis of overlapping pathophysiological mechanisms.*
Impact: If the association between male pattern baldness and fatal prostate cancer is substantiated in future studies, male pattern baldness may contribute to predictive algorithms of prostate cancer risk, helping guide individuals as to whether they should opt to undergo cancer screening.*
Biochimie. 2014 Feb;97:16-21. doi: 10.1016/j.biochi.2013.09.023. Epub 2013 Oct 8.*
Prolactin and adipose tissue.*
Carré N1, Binart N2.*
Author information*
Abstract*
The pituitary lactogenic hormone prolactin (PRL) exerts various physiological actions in humans and rodents via its binding to a membrane receptor. Beside its role in lactation and reproduction, accumulating evidence suggests that PRL has a crucial impact on energy balance by acting on two key players, the pancreas and the adipose tissue. Adipose tissue is now recognized as an endocrine organ and its metabolic activity appears to play an important role in pathophysiology such as obesity and diabetes. White adipocytes store excess of energy in the form of triglycerides for future need while brown adipocytes metabolize lipids and glucose to produce heat, highlighting their different metabolic functionality. The plasticity of white adipose tissue, by the emergence of beige adipocytes, appears to be essential in energy homeostasis. PRL receptor deficient mice provided direct evidence that PRL signaling is involved in the regulation of adipogenesis affecting energy balance and metabolic adaptation most notably during development. Moreover, it was demonstrated that PRL signaling participates to brown adipose tissue differentiation and function, opening novel understanding of hormonal regulation of energy balance. This review summarizes our current knowledge about PRL signaling and its role on adipose tissue.*
Copyright © 2013 Elsevier Masson SAS. All rights reserved.*
KEYWORDS:*
Adipocyte; Metabolism; Prolactin*
Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression.*
quotes:*
"HFs and the sebaceous glands express functional receptors for stress-related hormones, which are able to modulate androgen metabolism in the sebaceous gland"*
"PRL has also been implicated in the pathogenesis of androgenetic alopecia25 by modulation of androgens, and hyperprolactemia is associated with an androgenetic alopecia-type hair loss pattern, along with hirsutism (in females)"*
"*
Although it remains to be clarified how PRL exerts its activities on human HFs, we show that PRL is a potent catagen-promoter of human HFs in vitro, with efficacy comparable to that of TGF-2,62 yet is lower than that of interferon-. 63 We also show that the catagen-promoting activity of PRL is independent of the hypothalamus-pituitary-adrenal axis and systemic hormone levels."*
"solation and Culture of Human Hair Follicles Excess anagen HFs from occipital human scalp skin, obtained with informed consent during routine hair transplant or face-lift surgery, were isolated and cultured within 24 hours after surgery as previously described by Philpott and colleagues.41 The total number of organcultured HFs in anagen VI stage was 180, derived from 12 different individuals 25 to 55 years of age. After separation of epidermis and dermis from subcutaneous fat under a binocular dissecting microscope, anagen HFs were isolated from the subcutis by using watchmaker's forceps. HFs were then cultured under serum-free conditions in a 24-well plate containing 500 l of Williams E medium supplemented with insulin, L-glutamine, hydrocortisone, streptomycin, and penicillin. Three follicles per well were incubated for 8 days at 5% CO2 with addition of 400 ng/ml of human recombinant PRL (R&D Systems). Medium was changed every second day. Cultured HFs without PRL served as vehicle controls. After 4 days in culture, human HFs were washed in phosphate-buffered saline and embedded in OCT for cryosectioning. Normal PRL levels in humans vary between nonpregnant females (30 to 80 ng/ml), pregnant females (150 to 600 ng/ml), and males (5 to 20 ng/ml).5,8,42"*
"Regarding perspectives, a studies have focused on various innovative pharmacologic targets, but also on some well known molecules. The role of prolactin receptor antagonists, as well as the regulators of thyroid hormones, deserves to be the subject of further research ."*
"However, in men presenting premature balding before the age of 30, a recent study has reported subnormal PRL serum levels.28 In women, hair loss (telogen effluvium) may also be seen as a side-effect of treatment with bromocriptine, a dopaminergic inhibitor of pituitary PRL secretion."*
"The role of PRL in human hair growth control is still unclear. Hyperprolactinemia is accompanied by an androgenetic alopecia-like hair loss pattern, amenorrhea, infertility, acne vulgaris, and hirsutism."*
"This may be related to the fact that PRL can increase adrenal androgen production, although it can attenuate 5--reductase activity both in vivo and in vitro."*
Beyond lactation and reproduction, PRL is now recognized to modulate immune responses, osmoregulation, angiogenesis via induction of vascular endothelial growth factor, development, and hair growth.2 - 10*
Mind the (Gender) Gap: Does Prolactin Exert Gender and/or Site-Specific Effects on the Human Hair Follicle?*
http://www.nature.co...id2009340a.html*
Tumour Necrosis Factor Alpha, Interferon Gamma and Substance P Are Novel Modulators of Extrapituitary Prolactin Expression in Human Skin Abstract*
Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p?=?0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p?=?0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) ? increased PRL IR in the epithelium of human HFs (p?=?0.044) while tumour necrosis factor (TNF) ? decreased both PRL and PRLR IR. This study identifies substance P, TNF? and IFN? as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses.*
Functional consequences of prolactin signalling in endothelial cells: a potential link with angiogenesis in pathophysiology?*
Abstract*
Prolactin is best known as the polypeptide anterior pituitary hormone, which regulates the development of the mammary gland. However, it became clear over the last decade that prolactin contributes to a broad range of pathologies, including breast cancer. Prolactin is also involved in angiogenesis via the release of pro-angiogenic factors by leukocytes and epithelial cells. However, whether prolactin also influences endothelial cells, and whether there are functional consequences of prolactin-induced signalling in the perspective of angiogenesis, remains so far elusive. In the present study, we show that prolactin induces phosphorylation of ERK1/2 and STAT5 and induces tube formation of endothelial cells on Matrigel. These effects are blocked by a specific prolactin receptor antagonist, del1-9-G129R-hPRL. Moreover, in an in vivo model of the chorioallantoic membrane of the chicken embryo, prolactin enhances vessel density and the tortuosity of the vasculature and pillar formation, which are hallmarks of intussusceptive angiogenesis. Interestingly, while prolactin has only little effect on endothelial cell proliferation, it markedly stimulates endothelial cell migration. Again, migration was reverted by del1-9-G129R-hPRL, indicating a direct effect of prolactin on its receptor. Immunohistochemistry and spectral imaging revealed that the prolactin receptor is present in the microvasculature of human breast carcinoma tissue. Altogether, these results suggest that prolactin may directly stimulate angiogenesis, which could be one of the mechanisms by which prolactin contributes to breast cancer progression, thereby providing a potential tool for intervention.*
Keywords: prolactin, prolactin receptor, endothelial cells, angiogenesis, pathophysiology*
Eur Cytokine Netw. 2004 Apr-Jun;15(2):99-104.*
Prolactin triggers pro-inflammatory immune responses in peripheral immune cells.*
Brand JM1, Frohn C, Cziupka K, Brockmann C, Kirchner H, Luhm J.*
Author information*
Abstract*
The peptide hormone prolactin (PRL) is produced by specialized cells in the anterior pituitary gland and in a number of sites outside the pituitary. Its biological actions consist of various roles in reproduction, lactation, and of a number of homeostatic biological activities that also include immune functions. Elevated serum PRL concentrations often correlate with abnormalities in immune responses. To determine the influence of PRL on human immune cells, human whole blood cultures were stimulated with lipopolysaccharide (LPS), supplemented with various concentrations of human recombinant PRL. We found that PRL, at concentrations achievable during pregnancy, anesthesia and medication, significantly amplified interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-alpha) synthesis in LPS-stimulated cultures, in a dose-dependent manner. Conversely, synthesis of the anti-inflammatory cytokine IL-10 only increased significantly at very high concentrations of supplemented PRL. PRL alone was not able to induce any measurable secretion of TNF-alpha, IL-10, or IL-12 in non-stimulated, whole blood cultures. However, we demonstrated that PRL, by itself or in combination with LPS, causes an increase in the binding activity of the transcription factors nuclear factor-kappaB (NFkappaB) and interferon regulatory factor-1 (IRF-1), which are known to promote TNF-alpha and IL-12 secretion. These data suggest that PRL promotes pro-inflammatory immune responses via NFkappaB and IRF-1, which may affect pathophysiological processes in physiological hyperprolactinemic states.*
PMID: 15319167 [PubMed - indexed for MEDLINE]*
Recent Prog Horm Res. 2002;57:435-55.*
Prolactin modulation of immune and inflammatory responses.*
Yu-Lee LY1.*
Author information*
Abstract*
Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse physiological functions via its effects on cellular processes such as proliferation, differentiation, and cell survival. All these activities are mediated by the PRL receptor (PRL-R), a member of the hematopoietin cytokine receptor superfamily. To understand PRL-dependent mitogenic signaling in T cells, we cloned PRL. PRL-R, one mediator of PRL signaling, signal transducer and activator of transcription (Stat) 5b, and a panel of PRL-inducible immediate early-response genes from T cells. We are employing one of these PRL-inducible genes, the transcription factor interferon regulatory factor-1 (IRF-1), a multifunctional immune regulator gene, as a tool to understand how PRL modulates T-cell proliferative responses. In investigating regulatory events along the PRL-R/Janus activating kinase (JAK)/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross talk between Stat and nuclear factor (NF)kappaB signaling pathways also regulates IRF-1 expression. In understanding how signaling pathways cross talk at the IRF-1 promoter, we obtained insights into how PRL can modulate immune and inflammatory responses. These findings have much broader implications, not only for cells in the immune system but also for other PRL-responsive cells and tissues.*
Full article:*http://www.endocrine..._modulation.pdf*
Prolactin: A versatile regulator of inflammation and autoimmune pathology*
Abstract*
Prolactin (PRL) has long been proposed as an immune-stimulating and detrimental factor in autoimmune disorders. However, recent findings have challenged this common view, showing that PRL does not play a crucial role in the development of experimental autoimmune encephalomyelitis, animal model for multiple sclerosis (MS), and even protects against adjuvant-induced model of rheumatoid arthritis (RA). In this review we provide a critical overview of data supporting a role for PRL in the regulation of immune responses. In addition, we focus on studies exploring the involvement of PRL in autoimmune diseases, such as systemic lupus erythematosus, MS and RA, in light of the recently-outlined regenerative properties of this hormone.*
The results suggest that plasma prolactin may be involved in the regulation of androgen receptor content in the benign prostate."*
From:*http://content.karge....asp?Doi=30314*
"Prolactin levels were found to be significantly higher in BPH patients."*
Prolactin is Fing us all over*
Prolactin wants you dead.*
Prolactin rises when you masturbate.*
Prolactin kills your hair.*
Prolactin increases your hairs sensitivity to DHT.*
A neutralizing prolactin receptor antibody whose in vivo application mimics the phenotype of female prolactin receptor-deficient mice*
Adult stem/progenitor cells are found in many tissues, where their primary role is to maintain homeostasis. Recent studies have evaluated the regulation of adult stem/progenitor cells by prolactin in various target tissues or cell types, including the mammary gland, the prostate, the brain, the bone marrow, the hair follicle, and colon cancer cells. Depending on the tissue, prolactin can either maintain stem cell quiescence or, in contrast, promote stem/progenitor cell expansion and push their progeny towards differentiation. In many instances, whether these effects are direct or involve paracrine regulators remains debated. This minireview aims to overview the current knowledge in the field.*
Transgenic Mice Overexpressing the Prolactin Gene Develop Dramatic Enlargement of the Prostate Gland*
Abstract*
An altered endocrine status of elderly men has been hypothesized to be important for development of prostate hyperplasia. The present study addresses the question whether increased PRL expression is of importance for development of prostate hyperplasia in mice. Three lines of PRL transgenic mice were generated having serum levels of PRL of approximately 15 ng/ml, 100 ng/ml, and 250 ng/ml, respectively. These mice developed dramatic enlargement of the prostate gland, approximately 20 times the normal prostate weight and they had a 4- to 5-fold increased DNA content. Histologically, the prostate glands in the transgenic mice were distended from secretion, and the amount of interstitial tissue was increased. The levels of testosterone and IGF-I were increased in the PRL transgenic animals. In mice overexpressing the bovine GH gene, displaying elevated IGF-1 levels, the prostate gland was slightly larger compared with normal mice, indicating that the effect of PRL was not primarily mediated through elevated plasma IGF-I levels. The present study suggests that PRL is an important factor in the development of prostate hyperplasia acting directly on the prostate gland or via increased plasma levels of testosterone.*
Affiliations*
Department of Physiology, Research Centre for Endocrinology and Metabolism, Göteborg University, Medicinaregatan 1F, S-413 90 Göteborg, Sweden (H.W., J.K., J.T.) and Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Sahlgrenska Hospital, S-413 45 Göteborg, Sweden (O.G.P.I.)*
Male pattern baldness in relation to prostate cancer-specific mortality: A prospective analysis in the NHANES I Epidemiologic Followup Study (NHEFS)*
Cindy Ke Zhou1, Paul H. Levine2, Sean D. Cleary2, Heather J. Hoffman2, Barry I. Graubard1, and Michael B. Cook1*
+ Author Affiliations*
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD;*
2Department of Epidemiology and Biostatistics, George Washington University, Washington, DC.*
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA*
Abstract*
Background: Androgenic action underlies prostate gland development and prostate cancer progression. However, the role of such in prostate carcinogenesis remains unclear. Results from studies that have quantitated pre-diagnostic, circulating androgens at a single time-point in relation to prostate cancer are inconsistent, possibly due to the failure to capture cumulative or relevant age-specific hormone exposure. Therefore, we used male pattern baldness as a proxy of long-term androgen exposure, and investigated the association between dermatologist-assessed male pattern baldness and prostate cancer-specific mortality in the NHANES-I Epidemiologic Followup Study (NHEFS).*
Methods: We included 4,316 men from NHEFS, who were 25-74 years, received dermatologic exams, and had no prior cancer diagnosis at baseline. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazards regression with age as the time-metric and baseline hazard stratified by age at baseline. A hybrid model was used to account for stratification and clustering of the survey design, while adjusting for variables used to calculate sample weights.*
Results: During follow-up (median = 21 years), 3,284 deaths occurred, 107 of which had the underlying cause of prostate cancer. Any degree of baldness was associated with a 56% increased risk of prostate cancer-specific mortality (HR = 1.56; 95%CI = 1.02, 2.37) and, specifically, moderate balding was associated with an 83% increased risk of the outcome (HR = 1.83; 95%CI = 1.15, 2.92), each compared with no balding. Conversely, male pattern baldness was not statistically significantly associated with all-cause mortality.*
Conclusion: Our analysis suggests that male pattern baldness is associated with an increased risk of fatal prostate cancer, and supports the hypothesis of overlapping pathophysiological mechanisms.*
Impact: If the association between male pattern baldness and fatal prostate cancer is substantiated in future studies, male pattern baldness may contribute to predictive algorithms of prostate cancer risk, helping guide individuals as to whether they should opt to undergo cancer screening.*
Biochimie. 2014 Feb;97:16-21. doi: 10.1016/j.biochi.2013.09.023. Epub 2013 Oct 8.*
Prolactin and adipose tissue.*
Carré N1, Binart N2.*
Author information*
Abstract*
The pituitary lactogenic hormone prolactin (PRL) exerts various physiological actions in humans and rodents via its binding to a membrane receptor. Beside its role in lactation and reproduction, accumulating evidence suggests that PRL has a crucial impact on energy balance by acting on two key players, the pancreas and the adipose tissue. Adipose tissue is now recognized as an endocrine organ and its metabolic activity appears to play an important role in pathophysiology such as obesity and diabetes. White adipocytes store excess of energy in the form of triglycerides for future need while brown adipocytes metabolize lipids and glucose to produce heat, highlighting their different metabolic functionality. The plasticity of white adipose tissue, by the emergence of beige adipocytes, appears to be essential in energy homeostasis. PRL receptor deficient mice provided direct evidence that PRL signaling is involved in the regulation of adipogenesis affecting energy balance and metabolic adaptation most notably during development. Moreover, it was demonstrated that PRL signaling participates to brown adipose tissue differentiation and function, opening novel understanding of hormonal regulation of energy balance. This review summarizes our current knowledge about PRL signaling and its role on adipose tissue.*
Copyright © 2013 Elsevier Masson SAS. All rights reserved.*
KEYWORDS:*
Adipocyte; Metabolism; Prolactin*
Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression.*
quotes:*
"HFs and the sebaceous glands express functional receptors for stress-related hormones, which are able to modulate androgen metabolism in the sebaceous gland"*
"PRL has also been implicated in the pathogenesis of androgenetic alopecia25 by modulation of androgens, and hyperprolactemia is associated with an androgenetic alopecia-type hair loss pattern, along with hirsutism (in females)"*
"*
Although it remains to be clarified how PRL exerts its activities on human HFs, we show that PRL is a potent catagen-promoter of human HFs in vitro, with efficacy comparable to that of TGF-2,62 yet is lower than that of interferon-. 63 We also show that the catagen-promoting activity of PRL is independent of the hypothalamus-pituitary-adrenal axis and systemic hormone levels."*
"solation and Culture of Human Hair Follicles Excess anagen HFs from occipital human scalp skin, obtained with informed consent during routine hair transplant or face-lift surgery, were isolated and cultured within 24 hours after surgery as previously described by Philpott and colleagues.41 The total number of organcultured HFs in anagen VI stage was 180, derived from 12 different individuals 25 to 55 years of age. After separation of epidermis and dermis from subcutaneous fat under a binocular dissecting microscope, anagen HFs were isolated from the subcutis by using watchmaker's forceps. HFs were then cultured under serum-free conditions in a 24-well plate containing 500 l of Williams E medium supplemented with insulin, L-glutamine, hydrocortisone, streptomycin, and penicillin. Three follicles per well were incubated for 8 days at 5% CO2 with addition of 400 ng/ml of human recombinant PRL (R&D Systems). Medium was changed every second day. Cultured HFs without PRL served as vehicle controls. After 4 days in culture, human HFs were washed in phosphate-buffered saline and embedded in OCT for cryosectioning. Normal PRL levels in humans vary between nonpregnant females (30 to 80 ng/ml), pregnant females (150 to 600 ng/ml), and males (5 to 20 ng/ml).5,8,42"*
"Regarding perspectives, a studies have focused on various innovative pharmacologic targets, but also on some well known molecules. The role of prolactin receptor antagonists, as well as the regulators of thyroid hormones, deserves to be the subject of further research ."*
"However, in men presenting premature balding before the age of 30, a recent study has reported subnormal PRL serum levels.28 In women, hair loss (telogen effluvium) may also be seen as a side-effect of treatment with bromocriptine, a dopaminergic inhibitor of pituitary PRL secretion."*
"The role of PRL in human hair growth control is still unclear. Hyperprolactinemia is accompanied by an androgenetic alopecia-like hair loss pattern, amenorrhea, infertility, acne vulgaris, and hirsutism."*
"This may be related to the fact that PRL can increase adrenal androgen production, although it can attenuate 5--reductase activity both in vivo and in vitro."*
Beyond lactation and reproduction, PRL is now recognized to modulate immune responses, osmoregulation, angiogenesis via induction of vascular endothelial growth factor, development, and hair growth.2 - 10*
Mind the (Gender) Gap: Does Prolactin Exert Gender and/or Site-Specific Effects on the Human Hair Follicle?*
http://www.nature.co...id2009340a.html*
Tumour Necrosis Factor Alpha, Interferon Gamma and Substance P Are Novel Modulators of Extrapituitary Prolactin Expression in Human Skin Abstract*
Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p?=?0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p?=?0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) ? increased PRL IR in the epithelium of human HFs (p?=?0.044) while tumour necrosis factor (TNF) ? decreased both PRL and PRLR IR. This study identifies substance P, TNF? and IFN? as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses.*
Functional consequences of prolactin signalling in endothelial cells: a potential link with angiogenesis in pathophysiology?*
Abstract*
Prolactin is best known as the polypeptide anterior pituitary hormone, which regulates the development of the mammary gland. However, it became clear over the last decade that prolactin contributes to a broad range of pathologies, including breast cancer. Prolactin is also involved in angiogenesis via the release of pro-angiogenic factors by leukocytes and epithelial cells. However, whether prolactin also influences endothelial cells, and whether there are functional consequences of prolactin-induced signalling in the perspective of angiogenesis, remains so far elusive. In the present study, we show that prolactin induces phosphorylation of ERK1/2 and STAT5 and induces tube formation of endothelial cells on Matrigel. These effects are blocked by a specific prolactin receptor antagonist, del1-9-G129R-hPRL. Moreover, in an in vivo model of the chorioallantoic membrane of the chicken embryo, prolactin enhances vessel density and the tortuosity of the vasculature and pillar formation, which are hallmarks of intussusceptive angiogenesis. Interestingly, while prolactin has only little effect on endothelial cell proliferation, it markedly stimulates endothelial cell migration. Again, migration was reverted by del1-9-G129R-hPRL, indicating a direct effect of prolactin on its receptor. Immunohistochemistry and spectral imaging revealed that the prolactin receptor is present in the microvasculature of human breast carcinoma tissue. Altogether, these results suggest that prolactin may directly stimulate angiogenesis, which could be one of the mechanisms by which prolactin contributes to breast cancer progression, thereby providing a potential tool for intervention.*
Keywords: prolactin, prolactin receptor, endothelial cells, angiogenesis, pathophysiology*
Eur Cytokine Netw. 2004 Apr-Jun;15(2):99-104.*
Prolactin triggers pro-inflammatory immune responses in peripheral immune cells.*
Brand JM1, Frohn C, Cziupka K, Brockmann C, Kirchner H, Luhm J.*
Author information*
Abstract*
The peptide hormone prolactin (PRL) is produced by specialized cells in the anterior pituitary gland and in a number of sites outside the pituitary. Its biological actions consist of various roles in reproduction, lactation, and of a number of homeostatic biological activities that also include immune functions. Elevated serum PRL concentrations often correlate with abnormalities in immune responses. To determine the influence of PRL on human immune cells, human whole blood cultures were stimulated with lipopolysaccharide (LPS), supplemented with various concentrations of human recombinant PRL. We found that PRL, at concentrations achievable during pregnancy, anesthesia and medication, significantly amplified interleukin (IL)-12 and tumor necrosis factor-alpha (TNF-alpha) synthesis in LPS-stimulated cultures, in a dose-dependent manner. Conversely, synthesis of the anti-inflammatory cytokine IL-10 only increased significantly at very high concentrations of supplemented PRL. PRL alone was not able to induce any measurable secretion of TNF-alpha, IL-10, or IL-12 in non-stimulated, whole blood cultures. However, we demonstrated that PRL, by itself or in combination with LPS, causes an increase in the binding activity of the transcription factors nuclear factor-kappaB (NFkappaB) and interferon regulatory factor-1 (IRF-1), which are known to promote TNF-alpha and IL-12 secretion. These data suggest that PRL promotes pro-inflammatory immune responses via NFkappaB and IRF-1, which may affect pathophysiological processes in physiological hyperprolactinemic states.*
PMID: 15319167 [PubMed - indexed for MEDLINE]*
Recent Prog Horm Res. 2002;57:435-55.*
Prolactin modulation of immune and inflammatory responses.*
Yu-Lee LY1.*
Author information*
Abstract*
Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse physiological functions via its effects on cellular processes such as proliferation, differentiation, and cell survival. All these activities are mediated by the PRL receptor (PRL-R), a member of the hematopoietin cytokine receptor superfamily. To understand PRL-dependent mitogenic signaling in T cells, we cloned PRL. PRL-R, one mediator of PRL signaling, signal transducer and activator of transcription (Stat) 5b, and a panel of PRL-inducible immediate early-response genes from T cells. We are employing one of these PRL-inducible genes, the transcription factor interferon regulatory factor-1 (IRF-1), a multifunctional immune regulator gene, as a tool to understand how PRL modulates T-cell proliferative responses. In investigating regulatory events along the PRL-R/Janus activating kinase (JAK)/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross talk between Stat and nuclear factor (NF)kappaB signaling pathways also regulates IRF-1 expression. In understanding how signaling pathways cross talk at the IRF-1 promoter, we obtained insights into how PRL can modulate immune and inflammatory responses. These findings have much broader implications, not only for cells in the immune system but also for other PRL-responsive cells and tissues.*
Full article:*http://www.endocrine..._modulation.pdf*
Prolactin: A versatile regulator of inflammation and autoimmune pathology*
Abstract*
Prolactin (PRL) has long been proposed as an immune-stimulating and detrimental factor in autoimmune disorders. However, recent findings have challenged this common view, showing that PRL does not play a crucial role in the development of experimental autoimmune encephalomyelitis, animal model for multiple sclerosis (MS), and even protects against adjuvant-induced model of rheumatoid arthritis (RA). In this review we provide a critical overview of data supporting a role for PRL in the regulation of immune responses. In addition, we focus on studies exploring the involvement of PRL in autoimmune diseases, such as systemic lupus erythematosus, MS and RA, in light of the recently-outlined regenerative properties of this hormone.*
The results suggest that plasma prolactin may be involved in the regulation of androgen receptor content in the benign prostate."*
From:*http://content.karge....asp?Doi=30314*
"Prolactin levels were found to be significantly higher in BPH patients."*
