The A118G single-nucleotide polymorphism in OPRM1 is a risk factor for asthma severity.

BACKGROUND: Although population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related µ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity. METHODS: We initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response. RESULTS: Among 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4+CD4+ effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4+ T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation. CONCLUSIONS: Without forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN.

VEGF-C/VEGFR-3 signalling in macrophages ameliorates acute lung injury.

BACKGROUND: Successful recovery from acute lung injury requires inhibition of neutrophil influx and clearance of apoptotic neutrophils. However, the mechanisms underlying recovery remain unclear. We investigated the ameliorative effects of vascular endothelial growth factor (VEGF)-C/VEGF receptor 3 (VEGFR-3) signalling in macrophages in lipopolysaccharide (LPS)-induced lung injury. METHODS: LPS was intranasally injected into wild-type and transgenic mice. Gain and loss of VEGF-C/VEGFR-3 signalling function experiments employed adenovirus-mediated intranasal delivery of VEGF-C (Ad-VEGF-C vector) and soluble VEGFR-3 (sVEGFR-3) or anti-VEGFR-3 blocking antibodies and mice with a deletion of VEGFR-3 in myeloid cells. RESULTS: The early phase of lung injury was significantly alleviated by the overexpression of VEGF-C with increased levels of bronchoalveolar lavage (BAL) fluid interleukin-10 (IL-10), but worsened in the later phase by VEGFR-3 inhibition upon administration of Ad-sVEGFR-3 vector. Injection of anti-VEGFR-3 antibodies to mice in the resolution phase inhibited recovery from lung injury. The VEGFR-3-deleted mice had a shorter survival time than littermates and more severe lung injury in the resolution phase. Alveolar macrophages in the resolution phase digested most of the extrinsic apoptotic neutrophils and VEGF-C/VEGFR-3 signalling increased efferocytosis via upregulation of integrin αv in the macrophages. We also found that incubation with BAL fluid from acute respiratory distress syndrome (ARDS) patients, but not from controls, decreased VEGFR-3 expression and the efficiency of IL-10 expression and efferocytosis in human monocyte-derived macrophages. CONCLUSIONS: VEGF-C/VEGFR-3 signalling in macrophages ameliorates experimental lung injury. This mechanism may also provide an explanation for ARDS resolution.

S100A9/CD163 expression profiles in classical monocytes as biomarkers to discriminate idiopathic pulmonary fibrosis from idiopathic nonspecific interstitial pneumonia.

Circulating monocytes have pathogenic relevance in idiopathic pulmonary fibrosis (IPF). Here, we determined whether the cell surface levels of two markers, pro-inflammatory-related S100A9 and anti-inflammatory-related CD163, expressed on CD14strongCD16- classical monocytes by flow cytometry could discriminate IPF from idiopathic nonspecific interstitial pneumonia (iNSIP). Twenty-five patients with IPF, 25 with iNSIP, and 20 healthy volunteers were prospectively enrolled in this study. The S100A9+CD163- cell percentages in classical monocytes showed a pronounced decrease on monocytes in iNSIP compared to that in IPF. In contrast, the percentages of S100A9-CD163+ cells were significantly higher in iNSIP patients than in IPF patients and healthy volunteers. In IPF patients, there was a trend toward a correlation between the percentage of S100A9+CD163- monocytes and the surfactant protein-D (SP-D) serum levels (r = 0.4158, [95% confidence interval (CI) - 0.02042-0.7191], p = 0.051). The individual percentages of S100A9+CD163- and S100A9-CD163+ cells were also independently associated with IPF through multivariate regression analysis. The unadjusted area under the receiver operating characteristic curve (ROC-AUC) to discriminate IPF from iNSIP was (ROC-AUC 0.802, 95% CI [0.687-0.928]), suggesting that these are better biomarkers than serum SP-D (p < 0.05). This preliminary study reports the first comparative characterization of monocyte phenotypes between IPF and iNSIP.

Nutrients exported from upland stream water enlarge perennial biomass crops.

Rawanbuki, a variety of Japanese butterbur (Petasites japonicus subsp. giganteus), grow naturally along the Rawan River, Hokkaido, northern Japan. Most plants reach 2-3 m in height and 10 cm in diameter in 2 months and are much larger than those grown along other rivers. We examined the hypothesis that nutrients exported from upland streams enhance the growth of the Rawanbuki. Nutrient concentrations, including nitrogen, phosphorus, and base cations, in the Rawan River were much higher than those in rivers of adjacent watersheds. High nutrient concentrations and moisture contents were found in soil along the Rawan River and a significant relationship was found between physicochemical soil conditions and aboveground biomass of butterburs. This indicates that extremely large Rawanbuki plants could be caused by these high nutrient concentrations and moisture contents in the soils. A manipulation experiment showed that fertilization simulated the growth environment along the Rawan River and enhanced the stem height and stem diameter of butterburs. This study concluded that the extremely large butterburs are caused by a large amount of nutrients exported from upland areas. These results are the first demonstration of the role of stream water nutrients in enlarging agricultural crops.

S100A9/CD163 Expression in Circulating Classical Monocytes in Chronic Obstructive Pulmonary Disease.

Although many studies have characterized polarity of macrophages in chronic obstructive pulmonary disease (COPD), limited information is available regarding cellular phenotypes of circulating monocytes in this condition. This study aimed to determine the influence of cigarette smoking and COPD on the cellular phenotype of circulating monocytes. Thirty-two patients with COPD and 36 healthy volunteers (n = 17 and 19 in nonsmokers and smokers with normal lung functions, respectively) were enrolled in this study. The expression of two cell surface markers, pro-inflammatory-related S100A9 and anti-inflammatory-related CD163, on classical monocytes was analyzed by flow cytometry. The percentage of CD14strongCD16- classical monocytes in circulating monocytes showed no difference among the three groups. The percentage of S100A9+, S100A9+CD163-, and S100A9+CD163+ cells in classical monocytes was significantly increased in COPD patients relative to nonsmoker controls. In contrast, the levels of S100A9-CD163+ cells were significantly decreased in smokers with normal lung functions and in COPD patients relative to that in nonsmokers. Multivariate analyses revealed an independent association between S100A9+ cell rates and COPD (exponent 1.0336, 95% confidence interval [CI] 1.0063-1.0617, p value < 0.05). In Receiver operating characteristic (ROC) analyses, the ratio of S100A9+CD163-/S100A9-CD163+ cells yielded a receiver operating characteristic-area under the curve of 0.719 (95% CI = 0.567-0.871) for discrimination between smokers with normal lung functions and COPD patients. In conclusion, our results demonstrated increased pro-inflammatory phenotypes in circulating classical monocytes in COPD, providing novel insights to elucidate their roles in the pathogenesis of COPD.

Elemental and mutational analysis of lung tissue in lung adenocarcinoma patients.

BACKGROUND: This study aimed to observe the association between trace element concentrations in lung tissue from lung adenocarcinoma cancer (LADC) patients and mutations in the epidermal growth factor receptor (EGFR) and KRAS genes. METHODS: LADC patients who had undergone lung resection were included in this study. Furthermore, twenty patients without lung cancer were included in this study as the control group. Samples were separately collected from both tumor and peritumor tissues. The mutational status was assessed for EGFR mutations, ALK rearrangements and KRAS mutations. Based on these analyses, patients were grouped into three groups: EGFR mutation, KRAS mutation and wild-type groups. The concentrations of various trace elements in the lung tissues were measured by a particle-induced X-ray emission (PIXE) system, and the results were analyzed for statistical significance. RESULTS: A total of 110 LADC patients were included in this study. The median age was 70 years, and 60% of the participants were female. Moreover, 18% and 20% of patients were EGFR- and KRAS-positive, respectively. Thirty-two trace elements were measured, and 18 trace elements were detectable. The concentrations of Fe, Co, Ni, Cu, Zn and Br were significantly higher in the KRAS mutation and wild-type groups than in the control group regardless of whether the samples were from tumor or peritumor tissues. For these 6 trace elements, the concentrations were significantly higher in smokers than in non-smokers. Considering the effect of smoking, differences in the trace element concentrations between each mutational group remained. CONCLUSIONS: Trace elements in the lung may play a role in development of LADC in both smokers and never-smokers. However, prospective studies with larger sample sizes are needed to support this hypothesis.

The Role of Histamine in the Pathophysiology of Asthma and the Clinical Efficacy of Antihistamines in Asthma Therapy.

Mast cells play a critical role in the pathogenesis of allergic asthma. Histamine is a central mediator released from mast cells through allergic reactions. Histamine plays a role in airway obstruction via smooth muscle contraction, bronchial secretion, and airway mucosal edema. However, previous clinical trials of H1 receptor antagonists (H1RAs) as a treatment for asthma were not successful. In recent years, type 2 innate immunity has been demonstrated to be involved in allergic airway inflammation. Allergic asthma is defined by IgE antibody-mediated mast cell degranulation, while group 2 innate lymphoid cells (ILC2) induce eosinophilic inflammation in nonallergic asthma without allergen-specific IgE. Anti-IgE therapy has demonstrated prominent efficacy in the treatment of severe allergic asthmatics sensitized with specific perennial allergens. Furthermore, recent trials of specific cytokine antagonists indicated that these antagonists were effective in only some subtypes of asthma. Accordingly, H1RAs may show significant clinical efficacy for some subtypes of allergic asthma in which histamine is deeply associated with the pathophysiology.

Elevated Periostin Concentrations in the Bronchoalveolar Lavage Fluid of Patients with Eosinophilic Pneumonia.

BACKGROUND: Eosinophilic pneumonia (EP) is characterized by massive pulmonary infiltration by eosinophils. Although serum periostin is a novel marker for eosinophil-dominant asthma, the upregulation of periostin in the airway of asthmatics is controversial. In this study, we examined whether periostin concentrations are elevated in the bronchoalveolar lavage fluid (BALF) of patients with EP. METHODS: BAL was performed in healthy volunteers and in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), and sarcoidosis. The periostin concentrations in the BALF were measured. RESULTS: The periostin concentration in the BALF increased significantly with pulmonary eosinophil ia and was higher in AEP and CEP patients than in healthy volunteers and sarcoidosis patients, even after adjusting the albumin concentration. In pulmonary eosinophilia, the periostin concentration correlated with the eosinophil and lymphocyte counts, the concentration of albumin, and the concentration of cytokines such as IL-5, IL-13, and transforming growth factor ß1. CONCLUSIONS: Although some blood leakage may be involved in the elevation of periostin in the BALF of EP, periostin can be induced locally, at least in part. Therefore, periostin may play a role in the development of EP.

Recombinant pyrin domain protein attenuates allergic inflammation by suppressing NF-κB pathway in asthmatic mice.

Pyrin domain (PYD), a subclass of protein motif known as the death fold, is frequently involved in inflammation and immune responses. PYD modulates nuclear factor-kappa B (NF-κB) signalling pathway upon various stimuli. Herein, a novel recombinant pyrin domain protein (RPYD) was generated. Its role and mechanism in inflammatory response in an ovalbumin (OVA) induced asthma model was investigated. After OVA challenge, there was inflammatory cell infiltration in the lung, as well as airway hyper-responsiveness (AHR) to inhaled methacholine. In addition, eosinophils increased in the bronchoalveolar lavage fluids, alone with the elevated levels of Th-2 type cytokines [interleukin (IL)-4, IL-5 and IL-13], eotaxin, and adhesion molecules. However, the transnasal administration of RPYD before the OVA challenge significantly inhibited these asthmatic reactions. Moreover, RPYD markedly suppressed NF-κB translocation, reduced phosphorylation of p38 MAPK, and thus attenuated the expression of intercellular adhesion molecule 1 and IL-6 in the BEAS-2B cells stimulated by proinflammatory cytokines in vitro. These findings indicate that RPYD can protect asthma host from OVA-induced airway inflammation and AHR via down-regulation of NF-κB and p38 MAPK activities. RPYD may be used as a potential medicine for the treatment of asthma in clinic.

Role of genetic variations of chitinase 3-like 1 in bronchial asthmatic patients.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1) are associated with bronchial severity and pulmonary function. CHI3L1 proteins are involved in both innate and adaptive immune responses; however, to date, the correlation of these SNPs and their age of onset of bronchial asthma has not been demonstrated. METHODS: To address the role of these genetic variations, 390 patients with well-controlled bronchial asthma and living in Japan were recruited, genotyped, and had a pulmonary function test performed on them in this study. To analyze the concentration levels of CHI3L1 protein, bronchial lavage fluids were examined. RESULTS: Forced expiratory volume in one second, %predicted (%FEV1), was significantly decreased in homozygotes of rs1214194 compared to heterozygotes and wild type. The age of onset of adult bronchial asthma was significantly younger in GG homozygotes of rs4950928 and AA homozygotes of rs1214194 than in the other two genotypes. The concentration of CHI3L1 protein in bronchial lavage fluid increased in both homozygotes of rs4950928 and rs1214194. CONCLUSIONS: Our study demonstrated that the homozygotes of rs4950928 and rs1214194 of CHI3L1 might predict an early onset of bronchial asthma and have the propensity to promote airway remodeling.Trial registration JMA-IIA00045 remodeling-ICS.

Changes in pulmonary function of residents in Sanriku Seacoast following the tsunami disaster from the Great East Japan Earthquake.

BACKGROUND: Residents in the district struck by the Great East Japan Earthquake Tsunami (GEJET) suffered from adverse living conditions and various pulmonary diseases. OBJECTIVES: To evaluate the influence of GEJET, we performed serial assessment of pulmonary function of approximately 10,000 residents in the district struck by GEJET. METHODS: Using a spirometer, we assessed the pulmonary function of approximately 10,000 residents older than 18 years in the Sanriku seacoast, which was struck by the tsunami. Measurements were performed in 2011 and 2012. RESULTS: We compared FVC (forced vital capacity) % pred. and FEV1 (forced expiratory volume in 1second) % pred. of subjects between 2011 and 2012, by serial spirometry. Of the 7053 subjects studied, including 2611 men and 4442 women, FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011. Physical indices including height, body weight and the body mass index (BMI) did not change significantly during this period. Smoking prevalence changed significantly between 2010, 2011, and 2012. Both FVC% pred. and FEV1% pred. of subjects who had quit smoking increased significantly on spirometry carried out in 2012, compared with those in 2011. CONCLUSIONS: The pulmonary function expressed as FVC% pred. and FEV1% pred. were significantly higher in 2012 than in 2011 among the subjects studied. The changes in the smoking status may be one of the reasons for the increase in values observed. However, other undetermined factors during recovery from a disaster might have resulted in improved pulmonary function.

Deficiency of protein-L-isoaspartate (D-aspartate) O-methyl-transferase expression under endoplasmic reticulum stress promotes epithelial mesenchymal transition in lung adenocarcinoma.

A prognostic association between the novel chaperone protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) and lung adenocarcinoma has recently been reported. Here, we evaluated the functional roles of PIMT in the progression of lung adenocarcinoma. PIMT expression was detectable in 6 lung adenocarcinoma cell lines: A549, H441, H460, H1650, Calu 1, and Calu 6 cell lines. In A549 and H441 cells, knockdown by PIMT using silencing RNA of PIMT (si-PIMT) and/or small hairpin-RNA (sh-PIMT) induced a decrease in the expression of E-cadherin with an increase in vimentin expression, indicating that the epithelial to mesenchymal transition (EMT) was induced. Cell mobility, including migration and invasion capability, was increased in sh-PIMT A549 stable and si-PIMT H441 cells compared to in control cells. Endoplasmic reticulum (ER) stress, such as Thapsigargin (Tg) stress and hypoxia, induced EMT in A549 cells but not in other cell types, with an increase in GRP78 expression, whereas overexpression of PIMT reduced the EMT and cell invasion under stress conditions. The expression of hypoxia inducible factor-1 alpha (HIF1α) and Twist increased in sh-PIMT A549 and si-PIMT H441 cells, and Tg stress increased HIF1α expression levels in A549 cells in a dose-dependent manner. Moreover, LW6, an HIF1α inhibitor, reduced EMT, cancer invasion, and the levels of Twist in sh-PIMT A549 cells. Our results indicate that deficiency of supplemental PIMT expression under ER stress facilitates EMT and cell invasion in some cell types of lung adenocarcinoma.

Distinct Profiles of CD163-Positive Macrophages in Idiopathic Interstitial Pneumonias.

BACKGROUND: The types of cells most significantly linked to individual subtypes of idiopathic interstitial pneumonias (IIPs) remain unclear. Few studies have examined CD163+ macrophages in IIPs. OBJECTIVE: We retrospectively aimed to immunohistochemically characterize the CD163+ macrophages in IIPs. METHODS: Paraffin-embedded lung tissue samples were obtained from 47 patients with IIPs, including idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (NSIP), and cryptogenic organizing pneumonia (COP), and 12 normal controls were immunohistochemically analyzed, using primary antibodies against CD68 and CD163 as indicators of pan and M2 macrophages, respectively. RESULTS: CD68+ macrophage density was significantly increased in the 3 subtypes of IIPs relative to that in the control group, although no difference was detected within the different IIPs. CD163+ macrophage density was significantly increased in NSIP and COP samples relative to that in IPF samples. The density ratio of CD163+ macrophages to CD68+ macrophages was significantly decreased in IPF/UIP samples relative to that in the others, while the densities in NSIP and COP were significantly higher than those in control cases. CONCLUSION: CD163+ macrophages show distinct profiles among IIPs, and the standardized numerical density is decreased in IPF cases that have poor prognoses.

Impact of the genetic variants of GLCCI1 on clinical features of asthmatic patients.

BACKGROUND: Several gene variants are associated with a response to an inhaled corticosteroids (ICSs) treatment in patients with bronchial asthma. A variant of the glucocorticoid-induced transcript 1 (GLCCI1) genes has previously been associated with decreased lung function improvement upon treatment with ICSs in patients with bronchial asthma. Another report has also demonstrated that this genetic biomarker did not influence the change in flow volume in 1 second. However, no studies have considered the treatment content and the GLCCI1 variants. We were able to determine the relationship between the pulmonary function and clinical features and the variant of the GLCCI1 in Japanese asthmatic patients receiving long-term ICS treatment. MATERIALS AND METHODS: In this study, 405 patients with bronchial asthma, who were receiving ICS and living in Japan, were recruited, genotyped and underwent pulmonary function tests. To identify the GLCCI1 protein expression cells, endobronchial biopsy specimens were examined. RESULTS: We found that the pulmonary function was not significantly different in the homozygotes compared to the wild types. Also, the homozygotes increased the risk of a sustained step-up of the asthma treatment when compared to the wild type and heterozygotes. GLCCI1-positive cells were localized to the bronchial epithelial cells. The amount of GLCCI1 protein that cultured epithelial cells harboring GLCCI1 variants produced was less than the GLCCI1 wild type in the presence of a corticosteroid. CONCLUSIONS: A worsening of pulmonary function caused by GLCCI1 variants could be prevented due to recently used medications based on new action mechanisms.

Case series on the association between blood levels and side effects of afatinib maleate.

PURPOSE: Afatinib maleate (AFA) is a second-generation, tyrosine kinase inhibitor (TKI) treatment for specific variants of non-small cell lung cancer exhibiting epidermal growth factor receptor (EGFR) mutations. In this study, we measured the blood AFA levels in six patients with lung cancer and investigated the association between blood levels and side effects of this drug. METHODS: The study subjects were patients who were administered AFA for non-small cell lung cancer. Of these subjects, six patients agreed to participate in the study. The starting dose of AFA was 40 mg/day. We measured trough blood AFA levels on day 1 and 3 after AFA administration, on day 8-12, and every month until AFA administration was discontinued. Side effects were evaluated according to the adverse event codialect standard (CTCAE v.4.0). RESULTS: A temporary discontinuation and/or reduction in AFA dose (within 2 months) because of diarrhea and stomatitis was needed in four patients. Mean blood AFA levels on day 8-12 in these four patients were significantly higher than in other patients (47.0 ± 9.5 vs. 24.4 ± 0.1 ng/mL, P = 0.017). In addition, mean renal function prior to AFA administration in these four patients was significantly lower than that in the other patients (49.0 ± 9.6 mL/min/1.73 m2 vs. 77.2 ± 9.0, P = 0.026). CONCLUSIONS: High blood AFA levels were associated with the early discontinuation and/or dose reduction of AFA because of untoward side effects, which may also be associated with decreased renal function.

Japanese guidelines for adult asthma 2017.

Adult bronchial asthma is characterized by chronic airway inflammation, and presents clinically with variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma induces airway remodeling, leading to intractable asthma. The number of patients with asthma has increased; however, the number of patients who die of asthma has decreased (1.2 per 100,000 patients in 2015). The goal of asthma treatment is to enable patients with asthma to attain normal pulmonary function and lead a normal life, without any symptoms. A good relationship between physicians and patients is indispensable for appropriate treatment. Long-term management by therapeutic agents and elimination of the causes and risk factors of asthma are fundamental to its treatment. Four steps in pharmacotherapy differentiate between mild and intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid, varying from low to high levels. Long-acting ß2-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonist are recommended as add-on drugs, while anti-immunoglobulin E antibody and oral steroids are considered for the most severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled ß2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by choosing treatment steps for asthma in accordance with the severity of exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-induced asthma, and pregnancy are also important issues that need to be considered in asthma therapy.

17ß-HSD Type 12-Like Is Responsible for Maturation-Inducing Hormone Synthesis During Oocyte Maturation in Masu Salmon.

The maturation-inducing hormone 17α,20ß-dihydroxy-4-pregnen-3-one (DHP) was first identified in the amago salmon. Although carbonyl reductase-like 20ß-hydroxysteroid dehydrogenase (CR/20ß-HSD) was reported to convert 17α-hydroxyprogesterone (17OHP) to DHP in rainbow trout, we previously found that CR/20ß-HSD messenger RNA (mRNA) was not upregulated in stimulated granulosa cells from masu salmon, which suggested that DHP is synthesized by a different enzyme. Accordingly, the current study aimed to identify the specific 20ß-hydroxysteroid dehydrogenase (20ß-HSD) responsible for DHP production by granulosa cells during final oocyte maturation in masu salmon. RNA sequencing was performed on granulosa layers that were isolated from ovarian follicles at 1 month before ovulation and incubated with or without forskolin, which was used to mimic luteinizing hormone, and ∼12 million reads were obtained, which yielded 71,062 contigs of >100 bp. tBlastx analysis identified 1 contig (#f103496) as similar to 17ß-hydroxysteroid dehydrogenase type 12 (hsd17ß12); however, because the full-length #f103496 sequence was different from hsd17ß12, it was termed hsd17ß12-like (hsd17ß12l). We found that mammalian cells transfected with full-length hsd17ß12l exhibited considerable 20ß-HSD activity, as indicated by efficient conversion of exogenous 17OHP to DHP. In addition, we found that hsd17ß12l mRNA levels were consistently low in follicles during vitellogenic growth; however, the levels increased significantly during final oocyte maturation. The levels of hsd17ß12l mRNA were also considerably increased in granulosa layers in which 20ß-HSD activity was induced by salmon pituitary extract. Therefore, we suggest that hsd17ß12l, not CR/20ß-HSD, is the 20ß-HSD responsible for DHP production by granulosa cells in masu salmon during final oocyte maturation.