Endokrinologikum Hamburg

Hamburg, Germany

Endokrinologikum Hamburg

Hamburg, Germany
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Janssen S.T.,Institute of Laboratory Medicine | Janssen O.E.,Endokrinologikum Hamburg
Molecular and Cellular Endocrinology | Year: 2017

Thyroid hormones are bound to three major serum transport proteins, thyroxin-binding globulin (TBG), transthyretin (TTR) and human serum albumin (HSA). TBG has the strongest affinity for thyroid hormones, TTR is also found in the cerebrospinal fluid and HSA is the most abundant protein in plasma. Combination defects of either a high affinity TTR or HSA variant do not compensate TBG deficiency, underscoring the dominant role of TBG among the thyroid hormone transport proteins. On the other hand, coexistence of raised affinity TTR and HSA variants causes an augmented hyperthyroxinemia. Variations in thyroid hormone transport proteins may alter thyroid function tests to mimic hypo- or hyperthyroidism. As affected individuals are clinically euthyroid and do not require treatment, identification of thyroid hormone transport protein defects is important to avoid unnecessary diagnostic and therapeutic interventions. Mammals share the multilayered system of thyroid hormone binding proteins with humans. Some of them, especially carnivores, do not express TBG. In dogs, this defect has been shown to be caused by a defective hepatocyte nuclear factor-1 binding site in the TBG promoter, preventing TBG synthesis in the liver. The major endogenous thyroid hormone metabolite 3-iodothyronamine (3-T1AM) exerts marked cryogenic, metabolic, cardiac and central nervous system actions. It is bound to apolipoproteinB-100 (ApoB100), possibly facilitating its cellular uptake via interaction with the low density lipoprotein-receptor. This review summarizes the handling of hydrophobic charged thyroid hormone signaling molecules and their metabolite 3-T1AM in aqueous body fluids and the advantages and limits of their serum distributor proteins. © 2017 Elsevier B.V.


Gellersen B.,Endokrinologikum Hamburg | Brosens J.J.,University of Warwick
Endocrine Reviews | Year: 2014

Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation and placental development. In contrast to most mammals, decidualization of the human endometrium does not require embryo implantation. Instead, this process is driven by the postovulatory rise in progesterone levels and increasing local cAMP production. In response to falling progesterone levels, spontaneous decidualization causes menstrual shedding and cyclic regeneration of the endometrium. A growing body of evidence indicates that the shift from embryonic to maternal control of the decidual process represents a pivotal evolutionary adaptation to the challenge posed by invasive and chromosomally diverse human embryos. This concept is predicated on the ability of decidualizing stromal cells to respond to individual embryos in a manner that either promotes implantation and further development or facilitates early rejection. Furthermore, menstruation and cyclic regeneration involves stem cell recruitmentandrenders the endometrium intrinsically capable of adapting its decidual response to maximize reproductive success. Herewereview the endocrine, paracrine, and autocrine cues that tightly govern this differentiation process. In response to activation of various signaling pathways and genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access to the decidua-specific regulatory circuitry. Once initiated, the decidual process is poised to transit through distinct phenotypic phases that underpin endometrial receptivity, embryo selection, and, ultimately, resolution of pregnancy. Wediscusshowdisorders that subvert theprogramming, initiation, or progression of decidualization compromise reproductive health and predispose for pregnancy failure. © 2014 by the Endocrine Society.


Weimar C.H.E.,University Utrecht | Macklon N.S.,University Utrecht | Macklon N.S.,University of Southampton | Post Uiterweer E.D.,University Utrecht | And 2 more authors.
Human Reproduction Update | Year: 2013

background: Mechanisms underlying early reproductive loss in the human are beginning to be elucidated. The migratory and invasive capacity of human endometrial stromal cells (ESCs) is increasingly recognized to contribute to the intense tissue remodelling associated with embryo implantation, trophoblast invasion and endometrial regeneration. In this review, we examine the signals and mechanisms that control ESC migration and invasion and assess how deregulation of these cell functions contributes to common reproductive disorders. methods: The PubMed database was searched for publications on motility and invasiveness of human ESCs in normal endometrial function and in reproductive disorders including implantation failure, recurrent pregnancy loss (RPL), endometriosis and adenomyosis, covering the period 2000-2012. results: Increasing evidence suggests that implantation failure and RPLinvolve abnormal migratory responses of decidualizing ESCsto embryo and trophoblast signals. Numerous reports indicate that endometriosis, as well as adenomyosis, is associated with increased basal and stimulated invasiveness of ESCs and their progenitor cells, suggesting a link between a heightened menstrual repair response and the formation of ectopic implants. Migration and invasiveness of ESCs are controlled by a complex array of hormones, growth factors, chemokines and inflammatory mediators, and involve signalling through Rho GTPases, phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways.conclusions: Novel concepts are extending our understanding of the key functions of ESCs in effecting tissue repair imposed by cyclic menstruation and parturition. Migration of decidualizing ESCs also serves to support blastocyst implantation and embryo selection through discriminate motile responses directed by embryo quality. Targeting regulatory molecules holds promise for developing new strategies for the treatment of reproductive disorders such as endometriosis and recurrent miscarriage; and harnessing the migratory capacity of progenitor mesenchymal stem cells in the endometrium may offer new opportunities in regenerative medicine. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Bartmann C.,University of Würzburg | Segerer S.E.,Endokrinologikum Hamburg | Rieger L.,Hospital of Landshut Achdorf | Kapp M.,University of Würzburg | And 2 more authors.
American Journal of Reproductive Immunology | Year: 2014

Problem: To date, a multiplicity of factors contributing to the establishment and progression of a successful pregnancy have been postulated. There is emerging evidence that decidual leukocytes could be decisive factors during pregnancy. Despite numerous investigations on immune cells in human early pregnancy decidua, little is known about the physiological composition and proportion of the various immune cell populations during the different phases of pregnancy. In this study, we therefore analyzed the proportion of the dominant decidual leukocytes in human tissue samples derived from all phases of pregnancy. Methods: Single cell suspensions were prepared from decidual samples from 205 patients at 6-40 weeks of gestation. Cell populations were analyzed by flow cytometry, and immune cell populations were quantified as percentage of decidual CD45+ cells. Results: There was generally no difference in immune cell counts comparing decidua of healthy gestations and those with systemic inflammation. Overall, the proportion of uNK cells continuously decreased, while the amount of monocytes, immature dendritic cells, and T cells increased until term. Striking modifications in cell counts were seen during the 7th week compared with the 6th and later weeks of gestation. Conclusion: Studying the proportion of decidual immune cells during pregnancy, we detected a unique pattern which could be useful to design novel therapies for pathological conditions during pregnancy. © 2013 John Wiley & Sons Ltd.


Weimar C.H.E.,University Utrecht | Kavelaars A.,University Utrecht | Brosens J.J.,University of Warwick | Gellersen B.,Endokrinologikum Hamburg | And 4 more authors.
PLoS ONE | Year: 2012

Background: The aetiology of recurrent miscarriage (RM) remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women. Methodology/Principal Findings: Monolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13), a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12) or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05) and compared to the migration in the presence of high-quality embryo (p<0.01). Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001). Conclusions: H-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM. © 2012 Weimar et al.


Gellersen B.,Endokrinologikum Hamburg | Reimann K.,Endokrinologikum Hamburg | Samalecos A.,Endokrinologikum Hamburg | Aupers S.,Endokrinologikum Hamburg | Bamberger A.-M.,University of Hamburg
Human Reproduction | Year: 2010

Background Extensive invasion of the maternal decidua by extravillous trophoblast is considered of critical importance for implantation and placentation in humans, the decidua being viewed as a passively invaded tissue. In this study, we examined whether decidual cells might contribute to the highly dynamic processes at the fetal-maternal interface by active movement.Method SPrimary endometrial stromal cells (ESCs) or the telomerase-immortalized ESC line, St-T1b, was induced to decidualize or was left undifferentiated. The AC-1M88 cell line served as a model for extravillous trophoblast cells. Motility of ESCs and trophoblast cells was monitored in transwell invasion and migration assays under co-culture conditions. Secretion of matrix metalloproteinases (MMPs) was assessed by gelatin zymography.Result SAC-1M88 cell invasiveness was unaffected by the presence of ESCs, irrespective of their decidualization status. Surprisingly, decidualized ESCs were significantly more invasive than undifferentiated cells, and this invasive activity was strongly enhanced when cells were cultured in direct contact with AC-1M88 cells. Conditioned medium from AC-1M88 cells also stimulated migration and invasion of ESCs. Secretion of MMP-2 and-9 by ESCs was increased upon decidualization.Conclusion SEnhanced motility and invasive capacity of decidualized ESCs in the presence of trophoblastic cells lead us to hypothesize a major contribution of the decidua in encapsulating the early conceptus and supporting subsequent trophoblast invasion. Our findings thus suggest a far more active role of the decidua in the implantation process than hitherto recognized.


Gellersen B.,Endokrinologikum Hamburg | Wolf A.,Endokrinologikum Hamburg | Kruse M.,Endokrinologikum Hamburg | Schwenke M.,Endokrinologikum Hamburg | Bamberger A.M.,University of Hamburg
Biology of Reproduction | Year: 2013

We have previously shown that the presence of trophoblast cells enhances invasiveness of decidualizing human endometrial stromal cells. The metastasis suppressor CD82, which has antimigratory function in tumor cells, is up-regulated in decidualizing endometrial stromal cells. CEACAM1 is expressed in trophoblast cells at the invasion front in early placenta and is considered proinvasive. Here, we investigate the role of CD82 and CEACAM1 in cocultures of the endometrial stromal cell line T-HESC and AC-1M88 trophoblast cells. In transwell migration assays, chemotaxis of AC-1M88 cells was stimulated by coplated T-HESC in the lower compartment or by the combination of heparin-binding EGF-like growth factor (HB-EGF), interleukin-1 beta (IL-1beta), and leukemia inhibitory factor (LIF), local factors present at the time of implantation. In an implantation model of AC-1M88 trophoblast spheroids on a monolayer of THESC, spheroid expansion was enhanced in the presence of HBEGF/IL-1beta/LIF. Silencing of CEACAM1 in AC-1M88 blunted this response. Chemotactic migration of T-HESC was stimulated by trophoblast secretions or HB-EGF/IL-1beta/LIF. These responses were suppressed by CD82 depletion in T-HESC. Proteome profiling revealed the presence of platelet-derived growth factor (PDGF)-AA in trophoblast supernatant. Chemotaxis of T-HESC toward PDGF-AA was significantly inhibited by CD82 silencing. Neutralization of PDGF-AA in AC-1M88 conditioned media reduced the chemotactic effect on T-HESC. In summary, we demonstrate a mutual stimulation of chemotactic migration between trophoblast and endometrial stromal cells and promigratory roles for the cell surface molecules CEACAM1 and CD82, which may serve to support tissue remodeling at the implantation site.n © 2013 by the Society for the Study of Reproduction, Inc.


The care of transsexual patients is a lifelong and honestly interdisciplinary task for health professionals. The knowledge of the diagnostic criteria and treatment guidelines is of enormous importance for the general practitioner. Transsexualism is not an issue of sexuality and not a disease in the traditional sense but rather a disorder of gender identity (gender dysphoria). Transsexual patients require multiprofessional medical and social assistance to enable them a suitable life in an appropriate quality. First of all, there is a need of diagnosis and psychotherapy of gender dysphoria by an experienced mental health professional. Prior cross sex hormonal treatment a written "Mental Health Professional's Documentation Letter for Hormone Therapy" is needed. Prior each hormone prescription a counselling and a screening for risk factors or accompanying diseases is recommended. Guidelines are published for the cross sex hormone treatment. The collaboration with a centre with well experienced health professionals or contact with Transgender teams for the treatment of transsexual patients is recommended. Transsexual patients require life-long multi-professional medical attention and care, and they will gratefully accept this offer.


Janssen O.E.,Endokrinologikum Hamburg
Deutsche Medizinische Wochenschrift | Year: 2011

History and admission findings: A 41-year-old woman had been treated with an antibiotic for a sore throat and a tender neck. Later, moderate hyperthyroidism developed and was treated with antithyroid drugs. She presented herself for further work-up when neck pain and malaise persisted. On palpation, the thyroid was tender and firm, but not enlarged. Signs and symptoms indicated moderate hyperthyroidism. Investigations: Laboratory findings included suppressed TSH, elevated thyroid hormones, and both elevated erythrocyte sedimentation rate and CRP. On ultrasound, the thyroid was found to be of normal size but severely hypoechoic. A thyroid scan showed low uptake of technetium. Treatment and course: The findings supported the diagnosis of subacute thyroiditis. Prednisolone treatment provided relief of pain within 2 days. The patient later developed hypothyroidism suggestive of Hashimoto's thyroiditis and required thyroxin supplementation. © 2011 Georg Thieme Verlag KG Stuttgart • New York.


Jacobeit J.W.,Endokrinologikum Hamburg
Gynakologische Praxis | Year: 2014

The care of transsexual patients is a lifelong and honestly interdisciplinary task for health professionals. The knowledge of the diagnostic criteria and treatment guidelines is of enormous importance for the health professional. Transsexualism is not an issue of sexuality and not a disease in the traditional sense but rather a disorder of gender identity (gender dysphoria). Transsexual patients require multiprofessional medical and social assistance to enable them a suitable life in an appropriate quality. First of all, there is a need of diagnosis and psychotherapy of gender dysphoria by an experienced mental health professional. Prior cross sex hormonal treatment a written "Mental Health Professional's Documentation Letter for Hormone Therapy" is needed. Prior each hormone prescription a counselling and a screening for risk factors or accompanying diseases is recommended. Guidelines are published for the cross sex hormone treatment. The collaboration with a centre with well experienced health professionals or contact with Transgender teams for the treatment of transsexual patients is recommended. Transsexual patients require life-long multi-professional medical attention and care, and they will gratefully accept this offer.

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