Role Of Hormones Research Articles

1431 SERUM β-HCG PREDICTS RECURRENCE POST RADICAL CYSTECTOMY

You have accessJournal of UrologyBladder Cancer: Invasive (I)1 Apr 20131431 SERUM β-HCG PREDICTS RECURRENCE POST RADICAL CYSTECTOMY James Douglas, Tamsin Drake, Matthew Sommerlad, and Simon Crabb James DouglasJames Douglas Southampton, United Kingdom More articles by this author , Tamsin DrakeTamsin Drake Southampton, United Kingdom More articles by this author , Matthew SommerladMatthew Sommerlad Southampton, United Kingdom More articles by this author , and Simon CrabbSimon Crabb Southampton, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2785AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer has been associated with ectopic production of the free beta subunit of the hormone, human chorionic gonadotrophin (β-HCG). In pregnancy β-HCG has angiogenic, endocrine and immunosuppressive roles. The objective was to investigate serum and tumor levels of β-HCG in predicting post-cystectomy outcomes in muscle invasive bladder cancer. METHODS Over 200 patients who had bladder cancer treated by cystectomy at a tertiary referral centre, over a 10-year period, had their archived tissue transformed into a tissue micro-array. An associated database was created including blood results for a postoperative β-HCG if performed. Immunohistochemistry was performed for β-HCG. Slides were scored, blinded to clinical details, using a validated scoring system by a pathologist and the lead researcher and discrepancies agreed. In the post-operative period where serum β-HCG was measured, a serum level above 2 IU/L was considered positive. Survival differences were determined by Kaplan-Meier analyses and the log rank test using SPSS software. RESULTS There were representative cores for 180 patients. 8.3% of patients overexpressed beta-HCG. Expression patterns did not predict survival and were not related to serum levels in the patients who subsequently underwent β-HCG serum measurement. 96 patients had post-operative serum β-HCG measurements. 49 patients had a positive blood test and of these 84% had tumour recurrence. Of the 47 patients who had a negative blood test only 23% had a recurrence. Patients who had a positive β-HCG (>2IU/L) had only a 25% 5-year overall survival compared with 68% in the negative group (P=<0.001). Similarly the recurrence free survival was significantly worse in patients who had a positive serum β-HCG with a 5 year RFS of only 26% compared to 75% in the serum negative group (P<0.000). After Cox regression analysis a raised serum β-HCG gave a hazard ratio of 2.99 (P=0.001). CONCLUSIONS Serum β-HCG may be of value as a predictor of recurrence post radical cystectomy and could be used as an adjunct to the surveillance systems currently in use. The lack of a relationship between postoperative serum β-HCG and tumoral β-HCG expression may imply separate processes at the point of tumor metastasis. Prospective studies to assess the role of β-HCG in bladder cancer are warranted. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e586 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Douglas Southampton, United Kingdom More articles by this author Tamsin Drake Southampton, United Kingdom More articles by this author Matthew Sommerlad Southampton, United Kingdom More articles by this author Simon Crabb Southampton, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

POLYMORPHISMS IN THE 5´ FLANKING REGION AND FIRST EXON OF INSULIN-LIKE GROWTH FACTOR 1 GENE IN SOUTHERN POPULATIONS OF BUFFALO

The Insulin-like Growth Factor 1 (IGF-1) system plays a critical endocrine role controlling nutrient metabolism in animals and it is a group of structurally-related polypeptides that regulate the growth of many types of mammalian cells. In liver, IGF-1 is dynamically regulated by lactation and energy balance. Less is known about the regulation of IGF-1 and IGF-binding protein mRNA in reproductive tissues and plays an important role in bovine follicular growth, acquisition of oocyte competence and embryo viability. The present study describes Polymorphisms in the IGF-1 Gene of Buffalo population in south of Iran. In order to characterization polymorphism, blood sample were collected from 95 buffalos from Ahvaz, Dezful, Shushtar, Shadegan and Susangerd cities. DNA extraction was based on Boom method and exon 1 of the IGF-1 gene was amplified to produce a 250 bp fragment. The amplified fragment were digested with Eco105I (SnaBI) restriction endonuclease. Also, the 265 bp of IGF-1 promoter in the 5’ Flanking Region was amplified and subsequently subjected to Single Strand Conformation Polymorphism (SSCP). The results were revealed one pattern (B) in digestion and all the five populations were monomorph. But, the populations exhibited three different SSCP patterns. It is possible that this gene has not exposed to selection and inbreeding is estimated high.

POLYMORPHISM OF INSULIN-LIKE GROWTH FACTOR 1 GENE IN NAJDI CATTLE POPULATIONS

The Insulin-like Growth Factor 1 (IGF-1) system plays a critical endocrine role controlling nutrient metabolism in dairy cattle and it is a group of structurally-related polypeptides that regulate the growth of many types of mammalian cells. In liver, IGF-1 is dynamically regulated by lactation and energy balance. Less is known about the regulation of IGF-1 and IGF-binding protein mRNA in reproductive tissues and plays an important role in bovine follicular growth, acquisition of oocyte competence and embryo viability. The present study describes polymorphism of IGF-1 gene in Najdi cattle populations. In order to characterization polymorphism, blood sample were collected from 84 Najdi cattles from Shadegan, Mahshar cities and Shushtar station. DNA extraction was based on Boom method and exons 1 of the IGF-1 gene were amplified to produce a 249 bp fragment. The amplified fragment were digested with Eco105I (SnaBI) restriction endonuclease and then subjected to electrophoretic separation in ethidium bromide-stained 2% agarose gel. The results were revealed two alleles, A and B. Three genotypes were observed, Frequencies were 2.38, 14.28 and 83.33% for AA, AB and BB, respectively. This gives frequencies of 0/0952 and 0/9048 for A and B alleles. The populations were in hardy-weinberg equilibrium. It is possible that this gene has not exposed to selection. The heterozygosity is low and inbreeding is estimated high.

Effect of Ghrelin on Hepatic IGF-Binding Protein-1 Production

Ghrelin plays key roles in energy homeostasis by central and peripheral actions that include effects on insulin signalling pathways in liver. Insulin is an important inhibitor of production by hepatocytes of insulin-like growth factor-binding protein-1 (IGFBP-1) which has an endocrine role to inhibit IGF availability. The effects of ghrelin, insulin, an AMPK activator, and an AMPK inhibitor on IGFBP-1 secretion were studied in H4-II-E rat liver cells. Ghrelin (100 nM) blocked the inhibitory effect of a maximally effective concentration of insulin (10 ng/mL) on IGFBP-1 secretion during a 5 h incubation period (P < 0.001) in the absence and presence of an AMPK inhibitor. Ghrelin, alone, had no effect on IGFBP-1 production, but enhanced secretion independently of insulin under conditions of AMPK activation (P < 0.001). In conclusion, IGFBP-1 is identified as a novel target of ghrelin action in liver that may contribute to its metabolic effects in obesity.

Endocrine Actions of Osteocalcin

Osteocalcin is the most abundant noncollagenous protein of bone matrix. Once transcribed, this protein undergoes posttranslational modifications within osteoblastic cells before its secretion, including the carboxylation of three glutamic residues in glutamic acid, which is essential for hydroxyapatite binding and deposition in the extracellular matrix of bone. Recent provocative data from experimental observations in mice showed that the circulating undercarboxylated fraction of osteocalcin increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral fat in both genders, while it enhances testosterone production by the testes in males. Moreover, both total and undercarboxylated osteocalcins increase following physical activity with potential positive effects on glucose tolerance. Despite that these evidences have been only in part confirmed in humans, further prospective investigations are needed to definitively establish the endocrine role of osteocalcin both in the general population and cohorts of patients with diabetes or other metabolic disorders.

Towards an integrative approach to understanding the role of chemerin in human health and disease

Chemerin is an adipocyte-secreted protein with autocrine/paracrine roles on adipose development and function as well as endocrine roles in metabolism and immunity. Following prochemerin secretion, protease-mediated generation of chemerin isoforms with a range of biological activities is a key regulatory mechanism controlling local, context-specific chemerin bioactivity. Together, experimental and clinical data indicate that localized and/or circulating chemerin expression and activation are elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. These elevations are positively correlated with deleterious changes in glucose, lipid, and cytokine homeostasis, and may serve as a link between obesity, inflammation and other metabolic disorders. This review highlights the current state of knowledge regarding chemerin expression, processing, biological function and relevance to human disease, particularly with respect to adipose tissue development, inflammation, glucose homeostasis and cardiovascular disease. Furthermore, it discusses study variability, deficiencies in current measurement, and questions concerning chemerin function in disease, with a special emphasis on techniques and tools used to properly assess chemerin biology. An integration of basic and clinical research is key to understanding how chemerin influences disease pathobiology, and whether modulation of chemerin levels and/or activity may serve as a potential method to prevent and treat metabolic diseases.

Food Intake and Nutrition During Pregnancy, Lactation and Weaning in the Dam and Offspring

ContentsIn mammalian species, the connection between reproduction and nutrition is undeniable and illustrated by numerous publications: its role concerning regulation of hormonal secretions, fertility, pregnancy outcome, lactation and neonatal development indeed retains the attention of the scientific community. The interest on the influence of nutrition in dog and cat reproductive physiology is growing. Awareness on the key aspects of feeding during critical periods like pregnancy, lactation and weaning is essential to optimize the reproductive performances in these species.

Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function

Renal injury induced by brain death is characterized by ischemia and inflammation and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 hours of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 hours of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain dead rats showed significant improvement in function over the first 2 to 4 days post transplantation compared to untreated brain dead animals. Gene microarray analysis after 2 hours of brain death without or with nitrite therapy showed the latter significantly altered the expression of about 400 genes. Ingenuity Pathway analysis indicated multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription and genes related to humoral immune responses. Thus, nitrite-therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

Histochemical Analyses of Anti‐Microbial Substances in Canine Perianal Skin with Special Reference to Glandular Structures

Circumanal glands are prominent features of the canine perianal skin, which are often located near to the sebaceous glands and apocrine glands. As the functional relevance of circumanal glands is yet unknown, we studied the localisation of sialic acids and anti-microbial substances (lysozyme, immunoglobulin A, lactoferrin, β-defensin) in these glandular structures by lectin histochemistry and immunohistochemistry. The glands exhibited a number of sialic acids that were linked to α2-6Gal/GalNAc and α2-3Galβ1-4GlcNAc. Additionally, lysozyme, lactoferrin and β-defensin could be demonstrated in the three types of skin glands, whereas IgA was only detectable in the apocrine glands. The results of the study suggest the specific significance of the circumanal glands. Independent of a certain endocrine role, their products may mainly function as protective agents to preserve the integrity of the anal region, considering that sialic acids and anti-microbial substances are important in defence mechanisms.

Emerging Roles of Angiopoietin-like 4 in Human Cancer

Angiopoietin-like 4 (ANGPTL4) is best known for its role as an adipokine involved in the regulation of lipid and glucose metabolism. The characterization of ANGPTL4 as an adipokine is largely due to our limited understanding of the interaction partners of ANGPTL4 and how ANGPTL4 initiates intracellular signaling. Recent findings have revealed a critical role for ANGPTL4 in cancer growth and progression, anoikis resistance, altered redox regulation, angiogenesis, and metastasis. Emerging evidence suggests that ANGPTL4 function may be drastically altered depending on the proteolytic processing and posttranslational modifications of ANGPTL4, which may clarify several conflicting roles of ANGPTL4 in different cancers. Although the N-terminal coiled-coil region of ANGPTL4 has been largely responsible for the endocrine regulatory role in lipid metabolism, insulin sensitivity, and glucose homeostasis, it has now emerged that the COOH-terminal fibrinogen-like domain of ANGPTL4 may be a key regulator in the multifaceted signaling during cancer development. New insights into the mechanistic action of this functional domain have opened a new chapter into the possible clinical application of ANGPTL4 as a promising candidate for clinical intervention in the fight against cancer. This review summarizes our current understanding of ANGPTL4 in cancer and highlights areas that warrant further investigation. A better understanding of the underlying cellular and molecular mechanisms of ANGPTL4 will reveal novel insights into other aspects of tumorigenesis and the potential therapeutic value of ANGPTL4.

Role of Insulin-like Growth Factor-1 in the Regulation of Skeletal Growth

The importance of the insulin-like growth factor (IGF)-I axis in the regulation of bone size and bone mineral density, two important determinants of bone strength, has been well established from clinical studies involving patients with growth hormone deficiency and IGF-I gene disruption. Data from transgenic animal studies involving disruption and overexpression of components of the IGF-I axis also provide support for a key role for IGF-I in bone metabolism. IGF-I actions in bone are subject to regulation by systemic hormones, local growth factors, as well as mechanical stress. In this review we describe findings from various genetic mouse models that pertain to the role of endocrine and local sources of IGF-I in the regulation of skeletal growth.

MECHANISMS IN ENDOCRINOLOGY: The endocrine role of the skeleton: background and clinical evidence

Based on the observation that diabetes, obesity, and hypogonadism influence bone metabolism, the existence of a feedback loop and a common regulation was postulated and an endocrine role ascribed to the skeleton. In the first part of this review, two pathways are described whereby adipose tissue acts on bone mass. In the first, leptin activates the sympathetic nervous system via serotonin and diminishes bone mass accrual. The second pathway functions via the activation of CART (CARTPT) and inhibits bone resorption. The first pathway leads to a decrease in bioactivity of the osteoblast-produced hormone osteocalcin (OC) (part 2). In its undercarboxylated form, OC acts on the three targets pancreas, adipose tissue, and gonads (part 3) and thereby causes an increase in insulin secretion and sensitivity, β-cell proliferation, and male fertility. Insulin (part 4) is part of a recently discovered regulatory feedback loop between pancreas and osteoblasts. It is a strong counterplayer of leptin as it causes a decrease in OPG expression and enhances bone resorption and OC decarboxylation. Numerous clinical studies (part 5) have shown associations of total and undercarboxylated OC and markers of energy metabolism. Interventional studies, to date only performed in murine models, have shown positive effects of OC administration on energy metabolism. Whether bone tissue has an even further-reaching endocrine role remains to be elucidated.

The Action of D-Dopachrome Tautomerase as an Adipokine in Adipocyte Lipid Metabolism

Adipose tissue is a critical exchange center for complex energy transactions involving triacylglycerol storage and release. It also has an active endocrine role, releasing various adipose-derived cytokines (adipokines) that participate in complex pathways to maintain metabolic and vascular health. Here, we found D-dopachrome tautomerase (DDT) as an adipokine secreted from human adipocytes by a proteomic approach. DDT mRNA levels in human adipocytes were negatively correlated with obesity-related clinical parameters such as BMI, and visceral and subcutaneous fat areas. Experiments using SGBS cells, a human preadipocyte cell line, revealed that DDT mRNA levels were increased in an adipocyte differentiation-dependent manner and DDT was secreted from adipocytes. In DDT knockdown adipocytes differentiated from SGBS cells that were infected with the adenovirus expressing shRNA against the DDT gene, mRNA levels of genes involved in both lipolysis and lipogenesis were slightly but significantly increased. Furthermore, we investigated AMP-activated protein kinase (AMPK) signaling, which phosphorylates and inactivates enzymes involved in lipid metabolism, including hormone-sensitive lipase (HSL) and acetyl-CoA carboxylase (ACC), in DDT knockdown adipocytes. The AMPK phosphorylation of HSL Ser-565 and ACC Ser-79 was inhibited in DDT knockdown cells and recovered in the cells treated with recombinant DDT (rDDT), suggesting that down-regulated DDT in adipocytes brings about a state of active lipid metabolism. Furthermore, administration of rDDT in db/db mice improved glucose intolerance and decreased serum free fatty acids levels. In the adipose tissue from rDDT-treated db/db mice, not only increased levels of HSL phosphorylated by AMPK, but also decreased levels of HSL phosphorylated by protein kinase A (PKA), which phosphorylates HSL to promote its activity, were observed. These results suggested that DDT acts on adipocytes to regulate lipid metabolism through AMPK and/or PKA pathway(s) and improves glucose intolerance caused by obesity.

The insulin-like growth factor (IGF) signaling axis and hepatitis C virus-associated carcinogenesis (Review)

Insulin-like growth factor (IGF) signaling plays an important autocrine, paracrine and endocrine role in growth promotion involving various tissues and organs. Synthesis of both IGFs (IGF-1 and IGF-2) in normal conditions takes place mainly in the liver even if the proteins can be produced in every cell of the human body. The alterations in the IGF signaling axis in human hepatocarcinogenesis are described, but mechanisms of the interactions between expression of oncogenic hepatitisC virus (HCV) proteins and components of the IGF system in progression of chronic hepatitis C to primary hepatocellular carcinoma (HCC) have been poorly recognised. In advanced stages of liver diseases, lowered serum levels of IGF-1 and IGF-2 have been documented. This was supposed to reflect significant damage to liver parenchyma, a decreased number of growth hormone receptors and a decreased genomic expression of IGF binding proteins (IGF BPs). In HCC, a decreased tissue expression of IGF-1, and an increased expression of IGF-1 receptor (IGF-1R) were noted, compared to the control. Potential mechanisms of augmented IGF-2 expression in HCC were also described and dysregulation of IGF signaling in HCC was concluded to occur predominantly at the level of IGF-2 bioavailability. The review aimed at presentation of involvement of IGF-1, IGF-1R and IGF BPs (mostly IGF BP-3 and IGF BP-6) in HCV-related hepatocarcinogenesis. Manifestation of various mRNA transcripts and IGF-1 proteins and their potential involvement in carcinogenesis are also discussed.

Extrapituitary production of anterior pituitary hormones: an overview

Protein hormones from the anterior pituitary gland have well-established endocrine roles in their peripheral target glands. It is, however, now known that these proteins are also produced within many of their target tissues, in which they act as local autocrine or paracrine factors, with physiological and/or pathophysiological significance. This emerging concept is the focus of this brief review.

Endocrine disruptive estrogens role in electron transfer: Bio-electrochemical remediation with microbial mediated electrogenesis

Bioremediation of selected endocrine disrupting compounds (EDCs)/estrogens viz. estriol (E3) and ethynylestradiol (EE2) was evaluated in bio-electrochemical treatment (BET) system with simultaneous power generation. Estrogens supplementation along with wastewater documented enhanced electrogenic activity indicating their function in electron transfer between biocatalyst and anode as electron shuttler. EE2 addition showed more positive impact on the electrogenic activity compared to E3 supplementation. Higher estrogen concentration showed inhibitory effect on the BET performance. Poising potential during start up phase showed a marginal influence on the power output. The electrons generated during substrate degradation might have been utilized for the EDCs break down. Fuel cell behavior and anodic oxidation potential supported the observed electrogenic activity with the function of estrogens removal. Voltammetric profiles, dehydrogenase and phosphatase enzyme activities were also found to be in agreement with the power generation, electron discharge and estrogens removal.

Evolution of the vertebrate pth2 (tip39) gene family and the regulation of PTH type 2 receptor (pth2r) and its endogenous ligand pth2 by hedgehog signaling in zebrafish development

In mammals, parathyroid hormone (PTH), secreted by parathyroid glands, increases calcium levels in the blood from reservoirs in bone. While mammals have two PTH receptor genes, PTH1R and PTH2R, zebrafish has three receptors, pth1r, pth2r, and pth3r. PTH can activate all three zebrafish Pthrs while PTH2 (alias tuberoinfundibular peptide 39, TIP39) preferentially activates zebrafish and mammalian PTH2Rs. We know little about the roles of the PTH2/PTH2R system in the development of any animal. To determine the roles of PTH2 and PTH2R during vertebrate development, we evaluated their expression patterns in developing zebrafish, observed their phylogenetic and conserved synteny relationships with humans, and described the genomic organization of pth2, pth2r, and pth2r splice variants. Expression studies showed that pth2 is expressed in cells adjacent to the ventral part of the posterior tuberculum in the diencephalon, whereas pth2r is robustly expressed throughout the central nervous system. Otic vesicles express both pth2 and pth2r, but heart expresses only pth2. Analysis of mutants showed that hedgehog (Hh) signaling regulates the expression of pth2 transcripts more than that of nearby gnrh2-expressing cells. Genomic analysis showed that a lizard, chicken, and zebra finch lack a PTH2 gene, which is associated with an inversion breakpoint. Likewise, chickens lack PTH2R, while humans lack PTH3R, a case of reciprocally missing ohnologs (paralogs derived from a genome duplication). The considerable evolutionary conservation in genomic structure, synteny relationships, and expression of zebrafish pth2 and pth2r provides a foundation for exploring the endocrine roles of this system in developing vertebrate embryos.

The trophoblast binucleate cell is the source of maternal circulating C-type natriuretic peptide during ovine pregnancy

Maternal plasma concentrations of C-type natriuretic peptide (CNP) and a co-secreted bioinactive amino-terminal fragment (NTproCNP) are elevated during ovine pregnancy. Although the uteroplacental unit has been implicated as a likely source of CNP, the relative contributions of specific uterine and placental tissues, and identity of the cellular site/s of production remain unknown. Therefore, we measured CNP and NTproCNP in intercaruncular uterine tissue and maternal (caruncle) and fetal (cotyledon) placental tissues throughout gestation. Concentrations of CNP forms in placental tissues greatly exceeded those in intercaruncular uterine tissue throughout pregnancy (P < 0.05). Mean caruncular concentrations (CNP 32 ± 4, NTproCNP 56 ± 6 pmol g−1) peaked at day 60 whereas in the cotyledon there was a progressive increase in CNP forms to peak values (CNP 66 ± 6, NTproCNP 134 ± 9 pmol g−1) at day 100–135 followed by a sharp decline just prior to term (day 143). At term CNP gene expression was 6-fold greater in placental tissue compared with intercaruncular uterine tissue. Changes in maternal plasma concentration of CNP forms closely followed those in cotyledonary tissue whereas fetal plasma levels fell progressively throughout gestation. Immunohistochemistry revealed staining in binucleate cells (BNC) and around placental blood vessels.CNP’s localization to the BNC suggests a novel endocrine role during pregnancy, in addition to its paracrine actions within the placental vasculature. The function of CNP in maternal circulation remains to be determined, but as proposed for other BNC products, may involve manipulation of maternal physiology and placental function to favour fetal growth.

Subcutaneous adipose tissue metabolism and pharmacology: a new investigative technique

According to the Fick principle, any metabolic or hormonal exchange through a given tissue depends on the product of blood flow by arteriovenous difference. Because adipose tissue plays dual storage and endocrine roles, regulation of adipose tissue blood flow (ATBF) is of pivotal importance. Monitoring ATBF in humans can be achieved through different methodologies, such as the (133)Xe washout technique, considered to be the "gold standard", as well as microdialysis and other methods that are not well validated as of yet. This report describes a new method, called "adipose tissue microinfusion" or "ATM", which simultaneously quantifies ATBF by combining the (133)Xe washout technique together with variations of ATBF induced by local infusion of vasoactive agents. The most appropriate site for ATM investigation is the subcutaneous adipose tissue of the anterior abdominal wall. This innovative method conveniently enables the direct comparison of the effects on ATBF of any vasoactive compound, drug, or hormone against a contralateral saline control. The ATM method improves the accuracy and feasibility of physiological and pharmacological studies on the regulation of ATBF in vivo in humans.

17Beta-estradiol affects the response of complement components and survival of rainbow trout ( Oncorhynchus mykiss) challenged by bacterial infection

Research on the endocrine role of estrogens has focused on the reproductive system, while other potential target systems have been less studied. Here, we investigated the possible immunomodulating role of 17β-estradiol (E2) using rainbow trout ( Oncorhynchus mykiss) as a model. The aims of the study were to examine a) whether estrogens can modulate immune gene transcription levels, and b) whether this has functional implications for the resistance of trout towards pathogens. Trout were reared from fertilization until 6 months of age under (1) control conditions, (2) short-term E2-treatment (6-month-old juveniles were fed a diet containing 20 mg E2/kg for 2 weeks), or c) long-term E2-treatment (twice a 2-h-bath-exposure of trout embryos to 400 μg 17β-estradiol (E2)/L, followed by rearing on the E2-spiked diet from start-feeding until 6 months of age). Analysis of plasma estrogen levels indicated that the internal estrogen concentrations of E2-exposed fish were within the physiological range and analysis of hepatic vitellogenin mRNA levels indicated that the E2 administration was effective in activating the endogenous estrogen receptor pathway. However, expression levels of the hepatic complement components C3-1, C3-3, and Factor H were not affected by E2-treatment. In a next step, 6-month-old juveniles were challenged with pathogenic bacteria ( Yersinia ruckeri). In control fish, this bacterial infection resulted in significant up-regulation of the mRNA levels of hepatic complement genes (C3-1, C3-3, Factor B, Factor H), while E2-treated fish showed no or significantly lower up-regulation of the complement gene transcription levels. Apparently, the E2-treated trout had a lower capacity to activate their immune system to defend against the bacterial infection. This interpretation is corroborated by the finding that survival of E2-treated fish under bacterial challenge was significantly lower than in the control group. In conclusion, the results from this study suggest that estrogens are able to modulate immune parameters of trout with functional consequences on their ability to cope with pathogens.