Experimental and clinical endocrinology最新文献

{"title":"Binding of 2-hydroxyestradiol and 4-hydroxyestradiol to the estrogen receptor of MCF-7 cells in cytosolic extracts and in nuclei of intact cells.","authors":"N Schütze,&nbsp;G Vollmer,&nbsp;W Wünsche,&nbsp;A Grote,&nbsp;B Feit,&nbsp;R Knuppen","doi":"10.1055/s-0029-1211311","DOIUrl":"https://doi.org/10.1055/s-0029-1211311","url":null,"abstract":"<p><p>The catechol estrogens (CE), 2-hydroxyestradiol (2-OH-E2) and 4-hydroxyestradiol (4-OH-E2) were analyzed for their binding affinity to the estrogen receptor of MCF-7 cells. Applying a competitive binding assay to cytosols prepared from MCF-7 breast cancer cells, we measured a relative binding affinity of 23% (2-OH-E2) and 26% (4-OH-E2) compared to E2. Nuclear binding assays with the same cell line demonstrated a high specific binding with Kd's of 0.31 nM (2-OH-E2) and 0.21 nM (4-OH-E2). The relative binding affinity measured was 25% and 42% for 2-OH-E2 and 4-OH-E2, respectively. Based on this nuclear binding it can be concluded that the estrogen receptor occupied by CE is bound within the nucleus and might therefore be transcriptionally active.</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 5","pages":"399-408"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18865036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deiodination of thyroid hormones. A 30 year perspective (Berthold Memorial Award Lecture 1994).","authors":"L E Braverman","doi":"10.1055/s-0029-1211304","DOIUrl":"https://doi.org/10.1055/s-0029-1211304","url":null,"abstract":"<p><p>It is truly a great honor to be the 1994 recipient of the Berthold Memorial Award from the German Endocrine Society which met in Würzburg, March 2-5. I am especially indebted to Drs. Köhrle and Wuttke for their kindness in making our visit to Würzburg so enjoyable and educational. Professor Berthold was the first to demonstrate the effects of a hormone on phenotypic expression when he transplanted testes to a castrated rooster, restoring its masculine appearance and behavior (Figure 1) (Berthold, 1849). Since 1960, when I joined the laboratory of the late Dr. Sidney H. Ingbar at the Thorndike Memorial Laboratory at the Boston City Hospital and Harvard Medical School, one of our major interest has been the peripheral metabolism of the thyroid hormones (Figure 2), especially the deiodination pathway (Figure 3). This review will be primarily based on our studies, although many other laboratories have made extremely important observations on thyroid hormone metabolism at the clinical, physiological, and molecular biological levels. I am indebted to many collaborators who have played major roles in many of the studies to be cited in this review. The principle colleagues are listed in Table 1. Since much of our work has been carried out simultaneously in rats, humans, and cell cultures, studies will be described under these three broad categories.</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 5","pages":"355-63"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18867041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale production of Ba(2+)-alginate-coated islets of Langerhans for immunoisolation.","authors":"P Gröhn,&nbsp;G Klöck,&nbsp;J Schmitt,&nbsp;U Zimmermann,&nbsp;A Horcher,&nbsp;R G Bretzel,&nbsp;B J Hering,&nbsp;D Brandhorst,&nbsp;H Brandhorst,&nbsp;T Zekorn","doi":"10.1055/s-0029-1211308","DOIUrl":"https://doi.org/10.1055/s-0029-1211308","url":null,"abstract":"<p><p>Islet xenografts immunisolated in alginate capsules have been proposed by many groups for clinical islet transplantation. However, diffusion limitations and the total volume of microcapsules required for transplantation are, among other things, factors which have so far prevented successful clinical application. In this study, these problems have been overcome by immobilisation of rat and porcine islets in a Ba(2+)-cross-linked alignate matrix using an air jet droplet generator technique in combination with subsequent density-gradient purification. This procedure leads to high yields of islets coated with a tailored, thin layer of cross-linked alginate which protects the islets against cytotoxic compounds present in human plasma. The recovery of encapsulated rat and porcine islets was about 70%. Empty capsules were nearly completely removed. Using this technique, the total volume of the resulting microcapsules increased only by a factor of about 1.5 compared to the volume of free islets. The technique can be used for large-scale production of coated islets.</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 5","pages":"380-7"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18867045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The equine placenta and equine chorionic gonadotrophin--an overview.","authors":"H O Hoppen","doi":"10.1055/s-0029-1211287","DOIUrl":"https://doi.org/10.1055/s-0029-1211287","url":null,"abstract":"<p><p>Chorionic gonadotrophins seem to be unique for primate and equid species. Unlike primates, the equine conceptus does not implant in the maternal uterine endometrium until around day 37 of pregnancy. At this time specialized cells of the trophoblast, organized in the embryonic girdle, invade the endometrium and become established in the endometrial stroma, forming the so-called endometrial cups. This migration of girdle cells is accompanied by their morphological transformation into large decidual-like cells and by the appearance of a gonadotrophic hormone in the mare's blood. There is convincing evidence today that the hormone is of chorionic origin; therefore the term equine Chorionic Gonadotrophin (eCG) seems to be more appropriate than the formerly used term Pregnant Mare Serum Gonadotrophin (PMSG). Secretion of eCG peaks between days 60 and 80 in pregnant mares, to decline gradually until day 130 of gestation, with pronounced inter-individual variation. There appear to be no hormonal regulatory mechanisms controlling eCG synthesis and secretion, suggesting that the size and the morphology of the endometrial cups are the limiting factors. Equine CG is a glycoprotein hormone, composed of noncovalently bound alpha- and beta-subunits. The alpha-subunit consists of 96 amino acids and is identical for eCG and the pituitary hormones eLH, eFSH, and eTSH. The beta-subunit is similar to beta-hCG in that both have a C-terminal extension. It is comprised of 149 amino acids and the peptide primary structure is identical to that of beta-eLH.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 3","pages":"235-43"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18989133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The primate placenta and human chorionic gonadotropin.","authors":"W E Merz","doi":"10.1055/s-0029-1211286","DOIUrl":"https://doi.org/10.1055/s-0029-1211286","url":null,"abstract":"<p><p>In the primate placenta various peptide and proteohormones are synthesized which control growth and development of the fetus as well as the exchange of nutrients and metabolic products between the mother and the fetus. In humans, maintenance of pregnancy in the first trimester depends on the synthesis of the bioactive glycoprotein hormone human chorionic gonadotropin (hCG). It is expressed in placenta by the syncytiothrophoblast of early pregnancy. In cell culture, hCG production seems to mark a certain step in the process of differentiation of cytotrophoblasts and choriocarcinoma cells. It is neither understood how hCG synthesis is initiated and maintained at the beginning of gestation nor what control mechanisms are responsible for the down-regulation of the synthesis at the end of the first trimester. Besides a long list of various other substances which have been described to act as intrinsic placental stimulators of hCG biosynthesis, gonadoliberin and gamma-aminobutyric acid seem to play an important role. This establishes to some extent an analogy to the regulation of gonadotropin synthesis in the central nervous system. Recently, a full-length form of functional LH/hCG receptors of approximately 80 kD has been found in term placenta suggesting autoregulation as a regulatory principle of hCG biosynthesis. In the first trimester placenta as well as in choriocarcinoma cells a truncated form (50 kd) of LH/hCG receptors seems to exist. In these cases, exogenous hCG was unable to down-regulate its own synthesis. The carbohydrate moiety of hCG influences folding, subunit assembly, circulatory half-life, receptor interaction and biological response. A surplus of glycosylation may prevent subunit assembly. Experimental deglycosylation induces a different conformation of hCG, which partly acquires antagonistic properties. Recent results indicate that cAMP, which increases transcription and mRNA stability, also expands the N-glycosylation capacity and thus may accomplish an over-all coordination of hCG biosynthesis including post-translational events.</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 3","pages":"222-34"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211286","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18990492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete remission of metastasized adrenocortical carcinoma under o,p'-DDD.","authors":"E Kornely,&nbsp;R Schlaghecke","doi":"10.1055/s-0029-1211265","DOIUrl":"https://doi.org/10.1055/s-0029-1211265","url":null,"abstract":"<p><p>The case of a 53 year old female patient with metastasized androgen producing adrenocortical carcinoma is presented. After initial adrenalectomy a local relapse had been treated by surgery and external irradiation. Solitary liver metastases had been resected repeatedly. Subsequently multiple liver metastases required systemic chemotherapy. Treatment with o,p'-DDD (initially 12 g/d, long term treatment 1.5-3 g/d) has resulted in a complete remission for nearly 4 years. Gastrointestinal side effects occurred initially but subsided with dose reduction of o,p'-DDD.</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 1","pages":"50-3"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19000228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-function relationship of glucose transporters catalyzing facilitated diffusion.","authors":"H G Joost,&nbsp;S Wandel,&nbsp;A Schürmann","doi":"10.1055/s-0029-1211315","DOIUrl":"https://doi.org/10.1055/s-0029-1211315","url":null,"abstract":"Most mammalian cells depend on a continuous supply of glucose as the predominant source of ATP generation and substrate storage. The uptake of glucose into cells requires specific carrier proteins catalyzing the diffusion of the hexose along a concentration gradient which is maintained by the intracellular phosphorylation of the hexose. Molecular cloning of a protein (GLUT 1) mediating the uptake of glucose into erythrocytes (Mueckler et al., 1985), and the subsequent identification of homologous genes (GLUT2-4) revealed that a small family of genes is responsible for facilitated diffusion of the hexose into mammalian cells (Bell et al., 1990). It is now known that these genes belong to a subfamily of the large superfamily of transport facilitators which also comprises several yeast hexose transporters, plant hexose-proton symporters, and some bacterial sugar-proton symporters (Marger and Saier, 1993; Sauer and Tanner, 1993).","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 6","pages":"434-8"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18888059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay.","authors":"H Jarry,&nbsp;S Leonhardt,&nbsp;C Gorkow,&nbsp;W Wuttke","doi":"10.1055/s-0029-1211317","DOIUrl":"https://doi.org/10.1055/s-0029-1211317","url":null,"abstract":"<p><p>Women suffering from premenstrual mastodynia often respond to stimuli of prolactin (Prl) release with a hypersecretion of this hormone. Pharmacological reduction of Prl release by dopamine agonists or treatment with extracts of Agnus castus (AC) improve the clinical situation of patients with such premenstrual symptoms. Extracts of AC contain compounds which inhibit in vivo Prl release in women as well as in vitro from dispersed rat pituitary cells. It is yet unknown whether this inhibitory action of AC is only exerted on Prl release or whether release of other pituitary hormones like LH and FSH is also affected. The effects of AC on LH and FSH release were examined in vitro using rat pituitary cell cultures. To rule out that the Prl-inhibiting properties of AC are at least in part due to a cytotoxic component, pituitary cell cultures were subjected to the MTT test. To assess whether the Prl inhibitory effect of AC preparations is due to compounds acting as dopamine (DA) agonists, we used the corpus striatum membrane DA receptor binding assay. Our results demonstrate for the first time that AC extract contains an active principle that binds to the D2 receptor. Thus, it is very likely that it is this dopaminergic principle which inhibits Prl release in vitro from rat pituitary cells. Furthermore we give evidence for the specificity of action of AC on hormone release, since gonadotropin secretion remained unaffected. The findings of the present study support the therapeutical usefulness of AC extracts for treatment of premenstrual mastodynia which is associated with hypersecretion of Prl. Furthermore, the beneficial effects of AC appear to be due to the inhibition of pituitary Prl release.</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 6","pages":"448-54"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18888061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical studies on specificity and affinity of the BB5-antibody against human parathyroid tissue.","authors":"U Joseph,&nbsp;H G Seesko,&nbsp;K Neumann,&nbsp;W Cance,&nbsp;S Wells,&nbsp;M Rothmund","doi":"10.1055/s-0029-1211318","DOIUrl":"https://doi.org/10.1055/s-0029-1211318","url":null,"abstract":"<p><p>Localisation of parathyroid tissue in hyperparathyroidism may be difficult with standard methods. Immunoscintigraphy, using radiolabeled antibodies against epitopes of human parathyroid cells, could be a promising alternative. Therefore, we studied the necessary preconditions, whether the so-called BB5-antibody, directed against parathyroid cell membranes possesses sufficient specificity and affinity to be employed in immunoscintigraphy. Specificity was tested immunohistochemically with APAAP-staining of 39 different human tissues. Additionally, an immunoscore-based quantitative comparison was performed to test the affinity of BB5-antibody for normal and pathologic parathyroid tissue. Specificity was proven by the fact that of all 39 tested tissue-types only the parathyroid tissue was BB5-positive. Normal parathyroid tissue showed a significantly higher affinity to the BB5-antibody than pathologic parathyroid tissue (p < 0.03). However, all tissue samples from primary or secondary hyperparathyroidism exhibited sufficient staining. We conclude that the BB5-antibody fulfills the necessary conditions to be tried for immunoscintigraphical localisation of the parathyroid glands.</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 6","pages":"455-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18888062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Okadaic acid indicates a major function for protein phosphatases in stimulus-response coupling of RINm5F rat insulinoma cells.","authors":"P Mayer,&nbsp;C Jochum,&nbsp;H Schatz,&nbsp;A Pfeiffer","doi":"10.1055/s-0029-1211297","DOIUrl":"https://doi.org/10.1055/s-0029-1211297","url":null,"abstract":"<p><p>Stimulus-induced insulin secretion involves the activation of several protein kinases within the beta cell. Most prominent are protein kinase A, protein kinase C and calcium/calmodulin-dependent protein kinases. Protein kinase action is functionally antagonized by protein phosphatases. The four ubiquious serine/threonine protein phosphatases are termed PP-1, PP-2A, -2B and -2C. PP-1 and PP-2A are in vivo parts of major protein complexes. These complexes presumably regulate the phosphatase activity and direct the enzyme to its site of action. Therefore, PP-1 and -2A could play an important role in controlling intracellular signal transmission. Two different toxins, okadaic acid and calyculin A, both from marine invertebrates, were recently discovered and identified as potent and highly specific inhibitors of PP-1 and PP-2A. Both compounds emerged as very useful tools for studying intracellular phosphorylation events. We took advantage of these substances to investigate the significance of protein phosphatase action in stimulus-induced insulin secretion. To avoid major complexity, we confined our study to the cAMP and the phosphoinositide signal pathway. Okadaic acid alone evoked virtually no secretory response. cAMP-dependent secretion was markedly enhanced by 1 microM okadaic acid. The stimulatory effect of okadaic acid was strongly dependent on the concentration of cAMP analoga. In contrast, insulin release caused by the cholinergic agonist carbachol was not influenced by okadaic acid. Calyculin A (10 nM) slightly increased cAMP-induced secretion, but its high toxicity prohibited accurate interpretation of the data. Our findings support the idea that serine/threonine phosphatases act as important regulators in stimulus response coupling.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":12104,"journal":{"name":"Experimental and clinical endocrinology","volume":"102 4","pages":"313-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0029-1211297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18815599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}