The Experts below are selected from a list of 1668 Experts worldwide ranked by ideXlab platform
Angelica Linden Hirschberg - One of the best experts on this subject based on the ideXlab platform.
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effects of testosterone and estrogen treatment on the distribution of Sex Hormone Receptors in the endometrium of postmenopausal women
Menopause, 2008Co-Authors: Hong Zang, Lena Sahlin, Britt Masironi, Angelica Linden HirschbergAbstract:OBJECTIVE: Our aim was to investigate the effects of the addition of testosterone to estrogen compared with those of estrogen alone on the expression and distribution of Sex Hormone Receptors in glands and stroma of the endometrium of postmenopausal women. DESIGN: An open, randomized clinical study with parallel group comparison was performed in the Women's Health Research Unit at a university hospital. Thirty-one postmenopausal women were given oral estradiol valerate (2 mg daily) or estradiol valerate in combination with testosterone undecanoate (40 mg every 2 days) for 3 months. Before and at the end of treatment, endometrial biopsy samples were obtained, and expressions of estrogen receptor (ER)-alpha, ER-beta, progesterone receptor isoforms A and B, and androgen receptor (AR) were evaluated by immunohistochemical analysis. RESULTS: At baseline, expressions of ER-alpha and progesterone Receptors were stronger in glands than in stroma, whereas the immunostaining of AR was stronger in stroma than in glands. After treatment, expressions of ER-alpha and progesterone Receptors were up-regulated in both glands and stroma by both treatments, but to a lesser extent in glands by combined treatment. The expression of ER-beta in glands was significantly higher with combined treatment than with estrogen alone. Moreover, AR immunostaining was significantly higher after combined treatment than after treatment with estrogen alone. CONCLUSIONS: Expressions of AR and ER-beta were stronger in glands of the endometrium of postmenopausal women after treatment with testosterone added to estrogen than after estrogen alone. In contrast, expressions of ER-alpha and progesterone Receptors were up-regulated in the endometrium with estrogen-alone treatment, whereas these expressions were less increased in glands after combined treatment. These data indicate that testosterone is involved in the regulation of Sex Hormone receptor expression in the postmenopausal endometrium and may therefore influence endometrial proliferation and differentiation.
Raouf A Khalil - One of the best experts on this subject based on the ideXlab platform.
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research into specific modulators of vascular Sex Hormone Receptors in the management of postmenopausal cardiovascular disease
Current Hypertension Reviews, 2009Co-Authors: Graciliano Do R A Nascimento, Yaskara V R Barros, Amanda K Wells, Raouf A KhalilAbstract:Cardiovascular disease (CVD) is more common in men and postmenopausal women than premenopausal women, suggesting vascular benefits of female Sex Hormones. Studies on the vasculature have identified estrogen Receptors ERa, ERβ and a novel estrogen binding membrane protein GPR30, that mediate genomic and/or non-genomic effects. Estrogen promotes endothelium-dependent relaxation by inducing the production/activity of nitric oxide, prostacyclin, and hyperpolarizing factor, and inhibits the mechanisms of vascular smooth muscle contraction including [Ca2+]i, protein kinase C, Rho kinase and mitogen-activated protein kinase. Additional effects of estrogen on the cytoskeleton, matrix metalloproteinases and inflammatory factors contribute to vascular remodeling. However, the experimental evidence did not translate into vascular benefits of menopausal Hormone therapy (MHT), and the HERS, HERS-II and WHI clinical trials demonstrated adverse cardiovascular events. The discrepancy has been partly related to delayed MHT and potential changes in the vascular ER amount, integrity, affinity, and downstream signaling pathways due to the subjects age and preexisting CVD. The adverse vascular effects of MHT also highlighted the need of specific modulators of vascular Sex Hormone Receptors. The effectiveness of MHT can be improved by delineating the differences in pharmacokinetics and pharmacodynamics of natural, synthetic, and conjugated equine estrogens. Estriol, “Hormone bioidenticals” and phytoestrogens are potential estradiol substitutes. The benefits of low dose MHT, and transdermal or vaginal estrogens over oral preparations are being evaluated. Specific ER modulators (SERMs) and ER agonists are being developed to maximize the effects on vascular ERs. Also, the effects of estrogen are being examined in relation to the levels and effects of other Sex Hormones including progesterone and androgens. Thus, the experimental vascular benefits of estrogen can be translated to the outcome of MHT in postmenopausal CVD, as more specific modulators of Sex Hormone Receptors become available and are used at the right dose, route of administration and timing, depending on the subjects age and preexisting cardiovascular condition.
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modulators of vascular Sex Hormone Receptors and their effects in estrogen deficiency states associated with menopause
Recent Patents on Cardiovascular Drug Discovery, 2008Co-Authors: Michelle Serock, Amanda K Wells, Raouf A KhalilAbstract:Cardiovascular disease (CVD) is more prevalent in postmenopausal than premenopausal women, suggesting vascular protective effects of estrogen. Also, experimental studies have demonstrated beneficial effects of estrogen in improving vascular function and reducing vascular injury. However, clinical trials including HERS I, HERS II, WHI and WISDOM have demonstrated minimal beneficial vascular effects of menopausal Hormone therapy (MHT) in postmenopausal women with CVD. The discrepancies between the experimental findings and clinical data may be related to the vascular estrogen Receptors (ER), the type, route of administration, or dosage of MHT, and subjects age. Vascular ERs mediate both genomic and non-genomic effects of estrogen on the endothelium, vascular smooth muscle (VSM), and extracellular matrix (ECM). Postmenopausal changes in vascular ER structure, polymorphisms, amount, subcellular location, affinity or signaling could modify their responsiveness to estrogen and thereby the outcome of MHT. Recent investigations and patents have been centered on developing new ER modulators and alternatives for the traditional natural and synthetic forms of MHT which carry the risk of invasive breast cancer and venous thromoboembolism. Phytoestrogens may have similar effects as traditional MHT and have not demonstrated harmful side effects. Specific estrogen receptor modulators (SERMs) such as raloxifene and tamoxifen have also been tested. ER agonists that selectively target ERα, ERβ and perhaps GPR30 may modify specific vascular signaling pathways. Also, the dose, route of administration, and timing of MHT are integral to optimizing the beneficial effects and minimizing the side effects of MHT. Progesterone, testosterone and modulators of their specific Receptors may also affect the overall vascular effects of MHT in estrogen-deficiency states associated with menopause.
Hong Zang - One of the best experts on this subject based on the ideXlab platform.
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effects of testosterone and estrogen treatment on the distribution of Sex Hormone Receptors in the endometrium of postmenopausal women
Menopause, 2008Co-Authors: Hong Zang, Lena Sahlin, Britt Masironi, Angelica Linden HirschbergAbstract:OBJECTIVE: Our aim was to investigate the effects of the addition of testosterone to estrogen compared with those of estrogen alone on the expression and distribution of Sex Hormone Receptors in glands and stroma of the endometrium of postmenopausal women. DESIGN: An open, randomized clinical study with parallel group comparison was performed in the Women's Health Research Unit at a university hospital. Thirty-one postmenopausal women were given oral estradiol valerate (2 mg daily) or estradiol valerate in combination with testosterone undecanoate (40 mg every 2 days) for 3 months. Before and at the end of treatment, endometrial biopsy samples were obtained, and expressions of estrogen receptor (ER)-alpha, ER-beta, progesterone receptor isoforms A and B, and androgen receptor (AR) were evaluated by immunohistochemical analysis. RESULTS: At baseline, expressions of ER-alpha and progesterone Receptors were stronger in glands than in stroma, whereas the immunostaining of AR was stronger in stroma than in glands. After treatment, expressions of ER-alpha and progesterone Receptors were up-regulated in both glands and stroma by both treatments, but to a lesser extent in glands by combined treatment. The expression of ER-beta in glands was significantly higher with combined treatment than with estrogen alone. Moreover, AR immunostaining was significantly higher after combined treatment than after treatment with estrogen alone. CONCLUSIONS: Expressions of AR and ER-beta were stronger in glands of the endometrium of postmenopausal women after treatment with testosterone added to estrogen than after estrogen alone. In contrast, expressions of ER-alpha and progesterone Receptors were up-regulated in the endometrium with estrogen-alone treatment, whereas these expressions were less increased in glands after combined treatment. These data indicate that testosterone is involved in the regulation of Sex Hormone receptor expression in the postmenopausal endometrium and may therefore influence endometrial proliferation and differentiation.
Mariusz Z Ratajczak - One of the best experts on this subject based on the ideXlab platform.
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human rhabdomyosarcoma cells express functional pituitary and gonadal Sex Hormone Receptors therapeutic implications
International Journal of Oncology, 2016Co-Authors: Agata Poniewierskabaran, Gabriela Schneider, Ahmed Abdelbasetismail, Frederic G Barr, Mariusz Z RatajczakAbstract:Evidence has accumulated that Sex Hormones play an important role in several types of cancer. Because they are also involved in skeletal muscle development and regeneration, we were therefore interested in their potential involvement in the pathogenesis of human rhabdomyosarcoma (RMS), a skeletal muscle tumor. In the present study, we employed eight RMS cell lines (three fusion positive and five fusion negative RMS cell lines) and mRNA samples obtained from RMS patients. The expression of Sex Hormone Receptors was evaluated by RT-PCR and their functionality by chemotaxis, adhesion and direct cell proliferation assays. We report here for the first time that follicle-stimulating Hormone (FSH) and luteinizing Hormone (LH) Receptors are expressed in established human RMS cell lines as well as in primary tumor samples isolated from RMS patients. We also report that human RMS cell lines responded both to pituitary and gonadal Sex Hormone stimulation by enhanced proliferation, chemotaxis, cell adhesion and phosphorylation of MAPKp42/44 and AKT. In summary, our results indicate that Sex Hormones are involved in the pathogenesis and progression of RMS, and therefore, their therapeutic application should be avoided in patients that have been diagnosed with RMS.
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human haematopoietic stem progenitor cells express several functional Sex Hormone Receptors
Journal of Cellular and Molecular Medicine, 2016Co-Authors: Ahmed Abdelbasetismail, Malwina Suszynska, Sylwia Borkowska, Mateusz Adamiak, Janina Ratajczak, Magda Kucia, Mariusz Z RatajczakAbstract:Evidence has accumulated that murine haematopoietic stem/progenitor cells (HSPCs) share several markers with the germline, a connection supported by recent reports that pituitary and gonadal Sex Hormones (SexHs) regulate development of murine HSPCs. It has also been reported that human HSPCs, like their murine counterparts, respond to certain SexHs (e.g. androgens). However, to better address the effects of SexHs, particularly pituitary SexHs, on human haematopoiesis, we tested for expression of Receptors for pituitary SexHs, including follicle-stimulating Hormone (FSH), luteinizing Hormone (LH), and prolactin (PRL), as well as the Receptors for gonadal SexHs, including progesterone, oestrogens, and androgen, on HSPCs purified from human umbilical cord blood (UCB) and peripheral blood (PB). We then tested the functionality of these Receptors in ex vivo signal transduction studies and in vitro clonogenic assays. In parallel, we tested the effect of SexHs on human mesenchymal stromal cells (MSCs). Finally, based on our observation that at least some of the UCB-derived, CD45− very small embryonic-like stem cells (VSELs) become specified into CD45+ HSPCs, we also evaluated the expression of pituitary and gonadal SexH Receptors on these cells. We report for the first time that human HSPCs and VSELs, like their murine counterparts, express pituitary and gonadal SexH Receptors at the mRNA and protein levels. Most importantly, SexH if added to suboptimal doses of haematopoietic cytokines and growth factors enhance clonogenic growth of human HSPCs as well as directly stimulate proliferation of MSCs.
Lena Sahlin - One of the best experts on this subject based on the ideXlab platform.
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effects of testosterone and estrogen treatment on the distribution of Sex Hormone Receptors in the endometrium of postmenopausal women
Menopause, 2008Co-Authors: Hong Zang, Lena Sahlin, Britt Masironi, Angelica Linden HirschbergAbstract:OBJECTIVE: Our aim was to investigate the effects of the addition of testosterone to estrogen compared with those of estrogen alone on the expression and distribution of Sex Hormone Receptors in glands and stroma of the endometrium of postmenopausal women. DESIGN: An open, randomized clinical study with parallel group comparison was performed in the Women's Health Research Unit at a university hospital. Thirty-one postmenopausal women were given oral estradiol valerate (2 mg daily) or estradiol valerate in combination with testosterone undecanoate (40 mg every 2 days) for 3 months. Before and at the end of treatment, endometrial biopsy samples were obtained, and expressions of estrogen receptor (ER)-alpha, ER-beta, progesterone receptor isoforms A and B, and androgen receptor (AR) were evaluated by immunohistochemical analysis. RESULTS: At baseline, expressions of ER-alpha and progesterone Receptors were stronger in glands than in stroma, whereas the immunostaining of AR was stronger in stroma than in glands. After treatment, expressions of ER-alpha and progesterone Receptors were up-regulated in both glands and stroma by both treatments, but to a lesser extent in glands by combined treatment. The expression of ER-beta in glands was significantly higher with combined treatment than with estrogen alone. Moreover, AR immunostaining was significantly higher after combined treatment than after treatment with estrogen alone. CONCLUSIONS: Expressions of AR and ER-beta were stronger in glands of the endometrium of postmenopausal women after treatment with testosterone added to estrogen than after estrogen alone. In contrast, expressions of ER-alpha and progesterone Receptors were up-regulated in the endometrium with estrogen-alone treatment, whereas these expressions were less increased in glands after combined treatment. These data indicate that testosterone is involved in the regulation of Sex Hormone receptor expression in the postmenopausal endometrium and may therefore influence endometrial proliferation and differentiation.