[1,25(OH)2-vitamin D3. The vitamin D hormone].
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Calcitriol↗
Biomedical subjects
F Jakob
Publications and source records attributed to F Jakob.
Cytokine response of human macrophage-like cells after contact with polyethylene and pure titanium particles.
The aim of this study was to establish a human macrophage cell culture system to examine the effect of polyethylene (PE) and titanium particles on cytokine release by macrophage-like cells (MLC) and to quantify this response with respect to the nature and concentration of particles. Human monocytic leukemia cells were differentiated under standard conditions with vitamin D3 and granulocyte macrophage-colony-stimulating factor. Cells were characterized by fluorescence-activated cell-sorter Scan of CD 14 expression analysis as well as a phagocytosis test exploiting fluorescence-labeled particles of bacteria] walls. To achieve a relevant contact between the floating PE particles (approximately 1 microm in size) and MLC, a rotation device was used (15 rotations/min) during incubation. The same was done with the titanium particles. Cell culture supernatants were then analyzed for interleukin (IL)-1beta, IL-8, and tumor necrosis factor (TNF)-alpha using the enzyme-linked immunosorbent assay technique in the absence or presence of particles. Rotation of incubated MLC alone did not influence the secretion of TNF-alpha, but it enhanced secretion of IL-1beta and IL-8 about 30-fold compared to background levels. Both PE and titanium particles significantly enhanced MLC cytokine release, the amount of which depended on the concentration of particles. Using 40 X 10(8) PE particles (0.7 x 10(8) titanium particles) and 10(6) MLC, the maximal release of IL-1beta was about 20-fold (7-fold titanium particles) higher than that of the rotating control sample. The stimulation of IL-8 release was 4-fold (3-fold titanium particles) and of TNF-alpha. 300-fold (170-fold titanium particles) compared to controls. MLC were viable (>90% cell survival) at concentrations less than 108 x 10(8) polyethylene particles per 10(6) MLC and 16 x 10(8) titanium particles per 10(6) MLC. Rotation per se as well as exposure to increasing concentrations of PE and titanium particles stimulates cytokine release (TNF-alpha, IL-1beta, IL-8) by macrophages in vitro. This in vitro model resembles the in vivo situation near arthroplasties, where implant particles make contact with inflammatory cells, such as macrophages. Cytokine release by macrophages may impair osteoblast function as well as stimulate bone resorption by osteoclasts and macrophages, thereby causing aseptic loosening of arthroplasties. Our in vitro model provides a reproducible human cell system that might shed light on the pathogenesis of particle disease and might serve as a reproducible in vitro test system for the biocompatibility of foreign materials.
Cell Culture Techniques↗
[TNF-alpha secretion by human macrophage-like cells in response to wear particles and its modification by drugs].
UNLABELLED: Tumour necrosis factor (TNF) is considered to be the initiator protein of particle disease leading to aseptic loosening of endoprostheses. The aim of the present study was to investigate the TNF response of the macrophage-like cells (MLC) to the periprosthetic particles typically found during revision surgery. For this purpose, particles of polyethylene (PE), pure titanium (Ti), chromium (Cr), cobalt (Co), alumina ceramic (Al2O3) and zirconium dioxide (ZrO2) were used. Additionally, the therapeutic effect of non-steroidal and steroidal drugs, biphosphonates and pentoxyfylline on PE particles was investigated with the aim of differentiating drugs with, from those without, a positive effect on aseptic loosening. METHOD: In an established macrophage model (Rader et al. 1999), THP1 cells (human monocytic cell line) were differentiated over a period of five days in the presence of vitamin D3 and GM-CSF in macrophage-like cells (MLC). To obtain a TNF profile of the different materials, 10(6) MLC were incubated with each of a range of different particle concentrations. For drug testing purposes 80 x 10(8) PE particles, which evoked a maximum TNF response, were applied together with increasing drug concentrations in the same manner. The supernatant was then investigated for TNF secretion using ELISA. RESULTS: It was found that the greatest TNF response was provoked by Co and PE particles, and was 25 and 23 times as high, respectively, in comparison with control. The smallest TNF secretion was seen with Al2O3 (4 x control) and ZrO2 (5 x control). At the recommended dose, non-steroidal anti-inflammatory drugs (NSAIDs) produced no decrease in TNF secretion. The biphosphonates, etidronate and ibendronate significantly reduced the TNF response of the PE-stimulated macrophages (by 1/7 and 1/5, respectively). Therapeutic doses of pentoxyfylline also led to a decrease of 1/5 in maximum TNF release. CONCLUSION: Ceramic articulating surfaces are superior to metal/metal or PE/PE matings in terms of the biological effects of their wear particles. At therapeutic doses, NSAIDs have no beneficial effect on the process of aseptic loosening. Certain biphosphonates and pentoxyfylline have a positive effect on aseptic loosening.
Biocompatible Materials↗
Selenoproteins are expressed in fetal human osteoblast-like cells.
Selenoproteins are involved in mechanisms of cell differentiation and defense. We investigated the expression of glutathione peroxidases, as well as other selenoproteins, in fetal human osteoblasts (hFOB-cells). Using 75-selenium metabolic labelling of viable hFOB-cells, we identified several selenoproteins in cell lysates of about 45-80 kDa and in the migration range of 14 kDa to 24 kDa. Cells expressed low mRNA levels of both cellular glutathione peroxidase and plasma glutathione peroxidase mRNA as analysed by Southern analysis of RT-PCR products. Basal cellular glutathione peroxidase enzyme activity in hFOB-cells (19.7 nmol NADPH oxidised per min and microg protein) was further increased 2.5-fold by the addition of 100 nM sodium selenite to the culture medium for 3 days. Furthermore, expression of selenoprotein P mRNA was demonstrated by RT-PCR. hFOB-cells did not show activities of the selenoproteins type I or type II 5'-deiodinase. In summary, we identified cellular glutathione peroxidase, plasma glutathione peroxidase and selenoprotein P among of a panel of several 75-selenium labelled proteins in human fetal osteoblasts. The expression of selenoproteins like glutathione peroxidases in hFOB-cells represents a new system of osteoblast antioxidative defense that may be relevant for the protection against hydrogen peroxide produced by osteoclasts during bone remodelling.
Antioxidants↗
Identification by differential display PCR of the selenoprotein thioredoxin reductase as a 1 alpha,25(OH)2-vitamin D3-responsive gene in human osteoblasts--regulation by selenite.
1 alpha, 25(OH)2 vitamin D3 (1,25(OH)2D3) is a potent hormone, stimulating bone cell growth and differentiation. In order to detect novel targets for 1,25(OH)2D3 action, we applied differential display PCR (ddPCR) to human fetal osteoblasts (FOB cells). By ddPCR analysis, we identified the selenoprotein thioredoxin reductase (TRR) as a 1,25(OH)2D3-responsive gene. In FOB cells, the response of TRR mRNA steady state levels to 1,25(OH)2D3 was fast and transient. Maximal stimulation was observed after one hour of 1,25(OH)2D3 treatment, thereafter TRR steady state mRNA levels declined to control levels. This transient response of TRR mRNA was not reflected at the TRR enzyme activity level upon treatment with 1,25(OH)2D3 for up to 48 h. Sodium selenite added to differentiated FOB cells increased TRR enzyme activity 2.6-fold, whereas no selenite effect on TRR mRNA steady state levels was measurable. Our data might provide a link between the induction of a differentiation program by 1,25(OH)2D3 and the expression of the selenium responsive TRR system in human osteoblasts.
Blotting, Northern↗
Reconstitution of squamous epithelium in Barrett's oesophagus with endoscopic argon plasma coagulation: a prospective study.
BACKGROUND: Barrett's oesophagus is a premalignant condition. Recent reports have suggested that laser coagulation or photodynamic therapy combined with acid suppression may induce reconstitution of squamous mucosa. However, a high percentage of residual glands remain in cases treated with both techniques. Argon plasma coagulation (APC) appears to be an attractive alternative to other thermoablative techniques. The aim of this study was to investigate the reconstitution of squamous epithelium in Barrett's oesophagus after APC. METHODS: Fifteen patients with histologically proven Barrett's oesophagus were included in a prospective study. After base-line documentation by videotaping and biopsies, Barrett's epithelium was treated by repeated APC at intervals of 4-6 weeks until complete squamous restoration was achieved. All patients were kept under high-dose proton pump inhibitor therapy. RESULTS: In 13 patients complete reconstitution of squamous epithelium was achieved. Buried glands after squamous restoration were detected transiently in only one case after the first session. As side effects seven patients had mild retrosternal discomfort. One patient reported severe retrosternal pain for 1 week. He then refused further APC sessions. Another patient was excluded because of noncompliance. During the follow-up period (6-13 months) recurrence of Barrett's epithelium was observed in one patient. CONCLUSIONS: APC is a suitable technique for achieving squamous restoration in Barrett's oesophagus. The rare occurrence of remaining buried glands may result from the homogeneous coagulation achieved by the ionized argon gas beam.
Barrett Esophagus↗
Expression pattern of gastrointestinal selenoproteins--targets for selenium supplementation.
There is experimental and epidemiological evidence for an association between low selenium levels and gastrointestinal cancer incidence, prevalence, and mortality. To identify targets for selenium supplementation in the human digestive tract, we examined mRNA expression of various selenocysteine-containing proteins in normal mucosa biopsy specimens. Tissue samples from the esophagus and from different sites of the stomach, small bowel, and colon were obtained during endoscopies of the upper and lower gastrointestinal tract. Northern blot analyses revealed a lack of cytosolic glutathione peroxidase mRNA but a differential mRNA expression pattern of gastrointestinal and plasma glutathione peroxidase, selenoprotein P, and thioredoxin reductase. Glutathione peroxidase and thioredoxin reductase activities were detected in the mucosa of all biopsies, but the differential pattern did not reflect the differential mRNA steady-state levels. In addition to gastrointestinal glutathione peroxidase, which was found to play a role in colon cancer resistance, we identified further gastrointestinal selenoproteins, which may be involved in gastrointestinal cell defense and cell differentiation.
Biopsy↗
Reverse transcriptase-polymerase chain reaction analysis of thyrocyte-relevant genes in fine-needle aspiration biopsies of the human thyroid.
Currently, fine-needle aspiration cytology is a valuable tool in the routine diagnosis of suspicious thyroid nodules. We present a very sensitive method for the molecular analysis of the expression of several genes important for normal thyroid function in parallel to the cytological diagnosis. We adapted reverse transcriptase polymerase chain reaction (RT-PCR) to amplify thyroid-typical mRNAs in samples of thyroid carcinoma cells as small as those obtained by fine-needle aspiration biopsy (FNAB), ie, 100-1000 cells, and applied this procedure to four routinely taken FNABs. Gene products such as thyroglobulin (Tg), thyroid-stimulating hormone-receptor (TSHr), sodium/iodide-symporter (NIS), type I iodothyronine-5'-deiodinase (DI), and type II iodothyronine-5'-deiodinase (DII) were analyzed. To establish RT-PCR protocols, serial dilutions of follicular thyroid carcinoma cells, FTC-133, which express these genes at low levels, were initially used for RNA isolation. Successful RNA isolation and reverse transcription were checked by the amplification of beta-actin mRNA. We detected the mRNAs coding for Tg in as little as 10 cells, for NIS in 100 cells, and for TSHr, DI, and DII in 10,000 cells. After preparing cytological smears of four routinely taken FNABs, all above-mentioned thyroid-typical mRNAs were observed by using the material remaining in the needle for RNA isolation followed by RT-PCR. This method offers the possibility of obtaining two different types of information from the same routinely taken thyroid FNAB: the cytological diagnosis and the expression pattern of several diagnostically relevant genes. Therefore, a more specific diagnosis could be rendered in the preoperative state, and may lead to more specific therapy.
Biopsy, Needle↗
The human analog of murine cystein rich protein 61 [correction of 16] is a 1alpha,25-dihydroxyvitamin D3 responsive immediate early gene in human fetal osteoblasts: regulation by cytokines, growth factors, and serum.
1Alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is a potent mediator of differentiation and maintenance of specific functions of osteoblasts. To detect novel targets for 1,25-(OH)2D3 action, we applied differential display PCR to human fetal osteoblast-like cells and identified the human analog of murine cystein rich protein 61 (hCYR61) as a 1,25-(OH)2D3-responsive immediate early gene in differentiated fetal osteoblast-like cells. The murine gene CYR61 is important for cell-cell and cell-matrix interactions, and it belongs to an emerging gene family of cysteine-rich proteins. hCYR61 messenger RNA (mRNA) steady-state levels were stimulated 11-fold by 10 nM 1,25-(OH)2D3 by 1 h and declined to control levels by 4 h. This transient stimulation of hCYR61 mRNA was not inhibited by cycloheximide but was prevented by actinomycin D, indicating that the 1,25-(OH)2D3 effect involves transcriptional events and does not require de novo protein synthesis. hCYR61 mRNA stability was not influenced by 1,25(OH)2D3, whereas cycloheximide treatment stabilized hCYR61 mRNA. FCS, as well as growth factors and cytokines such as basic fibroblast growth factor, epidermal growth factor, tumor necrosis factor alpha, and interleukin-1, strongly elevated hCYR61 mRNA steady-state levels within 1 h. hCYR61 mRNA was expressed also in primary human osteoblasts and osteosarcoma cell lines. Using a commercial tissue blot, hCYR61 mRNA was only observed in skeletal muscle. The fast and transient response of hCYR 61 to 1,25-(OH)2D3, serum, growth factors, and cytokines suggests an important role of hCYR61 for osteoblast function and differentiation.
Animals↗
[Selenoproteins in bone, gastrointestinal tract and thyroid gland of the human].
BASIS: Selenium is an essential trace element, which is incorporated as selenocysteine (secys) into specific proteins in a regulated fashion. In the presence of a hairpin loop structure within the 3' untranslated region of the mRNA the opal stop codon UGA is coding for selenocysteine. Selenoprotein functions are dependent on secys incorporation. Members of the family of deiodinases as well as the family of glutathione peroxidases, selenoprotein P and thioredoxin reductase are selenoproteins. DISCUSSION: Bone, the intestine and the thyroid rely on antioxidant systems against potential cell and DNA damage through endogenous and environmental peroxides and reactive oxygen species (ROS) potentially promoting inflammation and tumorigenesis. Optimized cell defense through antioxidant selenoproteins requires optimal selenium supplementation of the organism. We have analyzed the expression of selenoproteins in these tissues, thus providing molecular tools to further elucidate optimal selenium supply on a cellular level. CONCLUSION: Clinical intervention studies that focus on the development of disease must confirm the relevance of optimized selenium supply for the pathogenesis, prevention and therapy of metabolic bone disease as well as chronic (autoimmune) inflammation and tumorigenesis in the thyroid and intestine.
Bone and Bones↗
Steroids, fatty acyl-CoA, and sterols are substrates of 80-kDa multifunctional protein.
The 2.9-kb mRNA of 17 beta-hydroxysteroid dehydrogenase IV codes for an 80-kDa (737 amino acids) protein featuring domains that are not present in the other human 17 beta-hydroxysteroid dehydrogenases. The N-terminal part reveals conserved motifs of the short-chain alcohol dehydrogenase family. The central- and C-terminal domains are similar to peroxisomal enzymes for beta-oxidation of fatty acids and to sterol carrier protein 2. The 80-kDa protein is N-terminally cleaved to a 32-kDa fragment (amino acids 1-323). Both the 80-kDa and the N-terminal 32-kDa peptides are able to catalyze the dehydrogenation with steroids at the C17 position and with 3-hydroxyacyl-CoA. The central part of the 80-kDa protein (amino acids 324-596) catalyzes the 2-enoyl-acyl-CoA hydratase reaction with high efficiency. The C-terminal part of the 80-kDa protein (amino acids 597-737) facilitates the transfer of 7-dehydrocholesterol and phosphaidylcholine between membranes in vitro. The unique multidomain structure of the 80-kDa protein permits the catalysis of several reactions previously thought to be performed by complexes of different enzymes.
17-Hydroxysteroid Dehydrogenases↗
Expression of selenoproteins in various rat and human tissues and cell lines.
Various rat and human tissues and cell lines naturally exposed to endogenous or exogenous oxidative stress were examined for their pattern of selenoprotein transcripts. Selenoprotein P mRNA was mainly expressed in rat kidney, testis, liver and lung. In testis, a high phospholipid hydroperoxide glutathione peroxidase (PHGPx) but only a weak cytosolic glutathione peroxidase (cGPx) signal was obtained. In kidney, spleen, heart, liver and lung cGPx mRNA levels were higher than those of PHGPx and for both only weak signals were obtained with brain mRNA. The Northern blot results concerning the tissue distribution of cGPx in the rat were fully supported by activity measurements. None of the human tissues revealed a PHGPx mRNA signal, whereas selenoprotein P transcripts were present in all human tissues with the highest abundance in heart, liver, and lung, tissues which also exhibited strong cGPx signals. The gastrointestinal glutathione peroxidase (GPx-GI) was only expressed in human liver and colon liver. Liver, the organ that showed the broadest repertoire of selenoproteins, has to cope with reactive oxygen intermediates produced during detoxification reactions. Human cell lines of the myeloic system that may be exposed to oxidative stress during inflammatory processes showed distinct cGPx signals: epithelial cells showed low cGPx signals. Similar cGPx mRNA levels were found in normal human thyroid tissue and thyroid carcinoma cells. Among the human cell lines selenoprotein P expression was detected in HepG2 and HTh74 thyroid cells. Our data confirm the necessity of getting specific information on distinct tissue- and cell-specific patterns of selenoprotein expression as endpoints of selenium supply and biological function of the selenoprotein family. Analysis of total selenium contents of tissues or body fluids only provides integrative information on the global selenium status of individuals.
Animals↗
Primary biliary cirrhosis and gastric carcinoid: a rare association?
Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune disorders. Although antibodies against gastric parietal cells are found in nearly all PBC patients, autoimmune gastritis is only very rarely associated. We describe a woman with PBC in whom chronic autoimmune gastritis complicated by a large pedunculated gastric carcinoid tumor was found. Additionally, the patient had autoimmune thyroiditis. This was interpreted as the rare association of PBC with Schmidt's syndrome type III. The carcinoid tumor was removed endoscopically. We conclude from the case that an endoscopic screening for autoimmune gastritis should at least be performed in patients with PBC and autoimmune thyroiditis, keeping in mind the possible occurrence of a polyendocrinopathy and the potentially serious complication of a gastric carcinoid tumor.
Carcinoid Tumor↗
Local estradiol metabolism in osteoblast- and osteoclast-like cells.
Bone is an estradiol-responsive tissue. Estrogen withdrawal during the menopause causes loss of bone mass and clinically relevant osteoporosis in a third of all women. Sufficient or impaired local production, as well as degradation of estradiol in cells present in the bone microenvironment might be an important mechanism of rescue or might contribute to the development of osteoporosis, respectively. We therefore investigated aromatase and 17beta-hydroxysteroid dehydrogenase type IV (17beta-HSD IV) expression in osteoblast- and osteoclast-like cells. Aromatase mRNA was increasingly expressed in myeloid THP 1 cells differentiated along the monocyte/phagocyte pathway exploiting vitamin D and either granulocyte-macrophage-stimulating factor (GMCSF) or macrophage-stimulating factor (MCSF). In long-term cultures, when sequentially exposed to vitamin D (days 0-21) and GMCSF (days 5-10) and plated on collagen, the amount of expression of aromatase mRNA steadily increased along with the increasing expression of osteopontin mRNA, alpha(v) integrin mRNA, c-fms (MCSF-receptor) mRNA and multinucleated cells developing. The conversion of estradiol from testosterone (10(-7) M/l) in the supernatants of dishes mirrored changes in aromatase mRNA expression and by day 21 rose to 30,000 ng/10(7) cells/24 h. 17Beta-HSD IV mRNA expression was abundant in undifferentiated THP 1 cells and was decreased to approximately 50% by day 21. Unstimulated SV-40 immortalized fetal osteoblasts did not express aromatase mRNA, but the expression was stimulated by the addition of the phorbol ester phorbol myristate acetate (PMA). Unstimulated osteoblasts from primary cultures did not express aromatase mRNA. Osteoblast-like osteosarcoma cells MG 63 expressed faint levels of aromatase mRNA in contrast to the osteosarcoma cell line HOS 58. 17Beta-HSD IV mRNA was expressed in fetal osteoblasts as well as in osteoblasts from primary culture, MG 63 and HOS 58 cells. In summary, we can show the expression of estradiol metabolizing enzymes in cells which are present in the bone microenvironment. Impaired aromatase expression and/or enhanced expression of 17beta-HSD IV may contribute to the pathogenesis of osteoporosis.
17-Hydroxysteroid Dehydrogenases↗
Selected novel flavones inhibit the DNA binding or the DNA religation step of eukaryotic topoisomerase I.
Topoisomerases are involved in many aspects of DNA metabolism such as replication and transcription reactions. Camptothecins, which stabilize the covalent intermediate of topoisomerase I and DNA are effective, though toxic, drugs for cancer therapy. In this study, a new class of topoisomerase I inhibitors was identified, and their mode of action was characterized using recombinant human topoisomerase I preparations and human HL-60 leukemic cells. Quercetin and the related natural flavones, acacetin, apigenin, kaempferol, and morin, inhibit topoisomerase I-catalyzed DNA religation. In contrast to camptothecin, these compounds do not act directly on the catalytic intermediate and also do not interfere with DNA cleavage. However, formation of a ternary complex with topoisomerase I and DNA during the cleavage reaction inhibits the following DNA religation step. 3,3',4',7-Tetrahydroxy-substituted flavones stabilize the covalent topoisomerase I-DNA intermediate most efficiently. Enhanced formation of covalent topoisomerase I-DNA complexes was also demonstrated in human HL-60 cells. In contrast, synthetic 3,5'-dibromo- 4'-hydroxy-3-methylflavones bind selectively to topoisomerase I in its non-DNA-bound form and block the following DNA binding step. As a consequence, these synthetic flavonoids are capable of counteracting topoisomerase I-directed effects of camptothecin. Inhibition of DNA binding is obtained by voluminous hydrophobic substituents in 6-position of the flavone structure. Our data show that selective inhibitors of both half-reactions of topoisomerase I can be derived from the flavone structure.
Base Sequence↗
Alcohol withdrawal and dopamine receptor sensitivity after prolonged abstinence.
1. Forty-four male inpatients suffering from moderate to severe alcohol dependence (DSM-III-R and ICD-10) as well as 14 healthy controls entered this study. Individuals were classified according to the severity of their withdrawal symptoms during detoxification i.e. group 1) no withdrawal, group 2) autonomic hyperactivity, group 3) withdrawal delirium and group 4) controls. 2. During the 6th week of treatment, that is, when all patients were recovered, controlled abstinent, and several weeks away from the end of their withdrawal syndrome, dopamine receptor sensitivity was neuroendocrinologically assessed by stimulating human growth hormone (HGH) with apomorphine (APO). 3. In a repeated measures model ANOVA, the four groups differed significantly in their HGH release. However, when excluding the controls from the analysis and focusing on alcoholics only (group 1 - 3), the significant difference disappeared. Covariates such as age, weight, quantity of drinking and duration of dependence were not related to the dependent variable. 4. In conclusion, the first significant result (with controls) reflects a blunted HGH response in alcoholics. It confirms earlier reports. The second, non significant result with the alcohol dependents only, suggests that the severity of withdrawal is not reflected by the amount of HGH released. Therefore, in alcoholics, a reduced dopamine receptor function after six weeks of abstinence, as neuro-endocrinologically assessed with apomorphine, seems to be related to alcohol dependence rather than to the severity of alcohol withdrawal.
Adult↗
Polymyositis, alopecia universalis, and primary sclerosing cholangitis in a patient with Crohn's disease.
We report a 36-year-old man with Crohn's disease, primary sclerosing cholangitis, and alopecia universalis. Six years after the onset of intestinal disease, the patient developed severe muscular pain and weakness of the neck. Muscle biopsy revealed myositis. Immunosuppressive treatment led to a significant improvement of muscular symptoms. Myositis in inflammatory bowel disease appears to be an important differential diagnosis in corticoid myopathy. Both alopecia and polymyositis are rarely associated with inflammatory bowel disease; thus, they have to be discussed as extraintestinal manifestations.
Adult↗
Characterization of 17 beta-hydroxysteroid dehydrogenase IV.
17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) IV is coded by 2.9 kb mRNA translated to an 80 kDa protein which is N-terminally cleaved to a 32 kDa enzyme. The 17 beta-HSD IV is dedicated to steroid inactivation and reveals only 25% amino acid similarity with 17 beta-HSD I-III enzymes. Despite five Asn-Xaa-Ser/Thr (Xaa = unspecified amino acid) sites in the 80 kDa protein the enzyme is not glycosylated. The porcine 32 kDa 17 beta-HSD IV forms dimers of 75 kDa. The highest 17 beta-HSD IV mRNA expression and specific activities are found in liver and kidney followed by ovary and testes. In porcine gonads the immunofluorescence assigned the 17 beta-HSD IV to granulosa cells and to Leydig and Sertoli cells. As shown by the treatment with phorbol-myristate-acetate in vitamin D-differentiated monocytic leukemia THP1 cells, steroid synthesis and inactivation are regulated differentially by the protein kinase C pathway: an increase in aromatase is accompanied by a decrease in 17 beta-HSD IV mRNA levels.
17-Hydroxysteroid Dehydrogenases↗