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https://www.readbyqxmd.com/read/30312418/a-new-multi-system-disorder-caused-by-the-g%C3%AE-s-mutation-p-f376v
#1
Heike Biebermann, Gunnar Kleinau, Dirk Schnabel, Detlef Bockenhauer, Louise C Wilson, Ian Tully, Sarah Kiff, Patrick Scheerer, Monica Reyes, Sarah Paisdzior, John W Gregory, Jeremy Allgrove, Heiko Krude, Michael Mannstadt, Thomas J Gardella, Mehul Dattani, Harald Jüppner, Annette Grüters
Context: The alpha-subunit of the stimulatory G-protein (Gαs) links numerous receptors to adenylyl cyclase. Gαs, encoded by GNAS, is expressed predominantly from the maternal allele in certain tissues. Thus, maternal heterozygous loss-of-function mutations cause hormonal resistance, as in pseudohypoparathyroidism type Ia, while somatic gain-of-function mutations cause hormone-independent endocrine stimulation, as in McCune-Albright Syndrome. Objective: We here report two unrelated boys presenting with a new combination of clinical findings that suggest both gain and loss of Gαs function...
October 11, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/30149370/regulation-of-steroidogenic-function-of-mouse-leydig-cells-g-coupled-membrane-estrogen-receptor-and-peroxisome-proliferator-activated-receptor-partnership
#2
E Gorowska-Wojtowicz, P Dutka, M Kudrycka, P Pawlicki, A Milon, B J Plachno, W Tworzydlo, L Pardyak, A Kaminska, A Hejmej, B Bilinska, M Kotula-Balak
We tested whether G-coupled membrane estrogen receptor (GPER) and peroxisome proliferator activated receptor (PPAR) partnership exists and whether this interaction regulates mouse Leydig cell function. Mature and aged mice were treated with the antagonist of GPER (G-15; 50 μg/kg b.w). Leydig cells (MA-10) were treated with G-15 (10 nM) alone or in combination with peroxisome proliferator-activated receptor α or γ antagonists, respectively (PPARα, 10 μM; PPARγ, 10 μM). GPER blockage affected testis steroidogenic status via changes in lutropin and cholesterol levels as well as protein expression alterations of the lutropin receptor, acute steroidogenesis activating protein, translocator protein, and protein kinase A in mouse Leydig cells both in vivo and in vitro...
June 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/30074232/blood-serum-concentrations-of-gonadotropins-and-%C3%AE-subunit-in-patients-with-gonadotropinomas-in-relation-to-the-immunoreactivity-of-pituitary-adenoma
#3
Marek Pawlikowski Łódź, Maria Jaranowska, Jolanta Fryczak, Maciej Radek, Jacek Świętosławski, Jolanta Kunert-Radek, Katarzyna Winczyk
INTRODUCTION: Although the active gonadotropin-secreting pituitary adenomas are considered as very rare, the vast majority of pituitary tumours diagnosed as "nonfunctioning" express gonadotropins or their free β or α subunits. However, the systemic investigations comparing the serum concentrations of follitropin (FSH), lutropin (LH) and α-subunit (αSU) before surgery with the immunoreactivity of the respective substances in the excised tumours are still lacking. MATERIALS AND METHODS: Immunostaining of FSH, LH and αSU was compared in 43 surgically removed gonadotropin - expressing pituitary adenomas with serum concentrations of the above mentioned substances before surgery in the same patients...
August 3, 2018: Endokrynologia Polska
https://www.readbyqxmd.com/read/29778238/interplay-between-estrogen-related-receptors-and-steroidogenesis-controlling-molecules-in-adrenals-in-vivo-and-in-vitro-study
#4
A Pacwa, E Gorowska-Wojtowicz, A Ptak, P Pawlicki, A Milon, M Sekula, K Lesniak, B Bilinska, A Hejmej, M Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found...
July 2018: Acta Histochemica
https://www.readbyqxmd.com/read/28881870/corrigendum-for-misfolding-ectodomain-mutations-of-the-lutropin-receptor-increase-efficacy-of-hormone-stimulation
#5
(no author information available yet)
No abstract text is available yet for this article.
July 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28541398/efficacy-and-safety-of-follitropin-alfa-lutropin-alfa-in-art-a-randomized-controlled-trial-in-poor-ovarian-responders
#6
P Humaidan, W Chin, D Rogoff, T D'Hooghe, S Longobardi, J Hubbard, J Schertz
No abstract text is available yet for this article.
July 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28137754/efficacy-and-safety-of-follitropin-alfa-lutropin-alfa-in-art-a-randomized-controlled-trial-in-poor-ovarian-responders
#7
RANDOMIZED CONTROLLED TRIAL
P Humaidan, W Chin, D Rogoff, T D'Hooghe, S Longobardi, J Hubbard, J Schertz
STUDY QUESTION: How does the efficacy and safety of a fixed-ratio combination of recombinant human FSH plus recombinant human LH (follitropin alfa plus lutropin alfa; r-hFSH/r-hLH) compare with that of r-hFSH monotherapy for controlled ovarian stimulation (COS) in patients with poor ovarian response (POR)? SUMMARY ANSWER: The primary and secondary efficacy endpoints were comparable between treatment groups and the safety profile of both treatment regimens was favourable...
March 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/27387040/minireview-insights-into-the-structural-and-molecular-consequences-of-the-tsh-%C3%AE-mutation-c105vfs114x
#8
REVIEW
Gunnar Kleinau, Laura Kalveram, Josef Köhrle, Mariusz Szkudlinski, Lutz Schomburg, Heike Biebermann, Annette Grüters-Kieslich
Naturally occurring thyrotropin (TSH) mutations are rare, which is also the case for the homologous heterodimeric glycoprotein hormones (GPHs) follitropin (FSH), lutropin (LH), and choriogonadotropin (CG). Patients with TSH-inactivating mutations present with central congenital hypothyroidism. Here, we summarize insights into the most frequent loss-of-function β-subunit of TSH mutation C105Vfs114X, which is associated with isolated TSH deficiency. This review will address the following question. What is currently known on the molecular background of this TSH variant on a protein level? It has not yet been clarified how C105Vfs114X causes early symptoms in affected patients, which are comparably severe to those observed in newborns lacking any functional thyroid tissue (athyreosis)...
September 2016: Molecular Endocrinology
https://www.readbyqxmd.com/read/27307766/profile-of-follitropin-alpha-lutropin-alpha-combination-for-the-stimulation-of-follicular-development-in-women-with-severe-luteinizing-hormone-and-follicle-stimulating-hormone-deficiency
#9
REVIEW
Leonardo Rinaldi, Helmy Selman
A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary-hypogonadotropic women (World Health Organization Group I)...
2016: International Journal of Women's Health
https://www.readbyqxmd.com/read/26554443/misfolding-ectodomain-mutations-of-the-lutropin-receptor-increase-efficacy-of-hormone-stimulation
#10
E Charmandari, R Guan, M Zhang, L G Silveira, Q R Fan, G P Chrousos, A C Sertedaki, A C Latronico, D L Segaloff
We demonstrate 2 novel mutations of the LHCGR, each homozygous, in a 46,XY patient with severe Leydig cell hypoplasia. One is a mutation in the signal peptide (p.Gln18_Leu19ins9; referred to here as SP) that results in an alteration of the coding sequence of the N terminus of the mature mutant receptor. The other mutation (p.G71R) is also within the ectodomain. Similar to many other inactivating mutations, the cell surface expression of recombinant human LHR(SP,G71R) is greatly reduced due to intracellular retention...
January 2016: Molecular Endocrinology
https://www.readbyqxmd.com/read/26469117/brdt-bromodomains-inhibitors-and-other-modern-means-of-male-contraception
#11
REVIEW
Zygmunt Zdrojewicz, Radosław Konieczny, Paulina Papier, Filip Szten
Compared to efficient and secure female contraception, a vasectomy and condoms are the only options for men. The choice of male contraceptive methods is limited, so contraception mainly rests on the shoulders of women. Several concepts are considered: testosterone administration--inhibiting pituitary secretion of lutropin (LH) and follicle stimulating hormone (FSH), progestogen--affecting the secretion of gonadotropin and gonadoliberin (GnRH) antagonists. New potential targets for non-hormonal male contraception were discovered: glyceraldehyde-3-phosphate-dehydrogenase (GAPDHS)--specific to male germ cells and voltage-gated cation channel (CatSper)...
July 2015: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/26441830/differences-in-signal-activation-by-lh-and-hcg-are-mediated-by-the-lh-cg-receptor-s-extracellular-hinge-region
#12
Paul Grzesik, Annika Kreuchwig, Claudia Rutz, Jens Furkert, Burkhard Wiesner, Ralf Schuelein, Gunnar Kleinau, Joerg Gromoll, Gerd Krause
The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) - secreted by the placenta, and lutropin (LH) - produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor's leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones...
2015: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/26079838/bridge-technology-with-tsh-receptor-chimera-for-sensitive-direct-detection-of-tsh-receptor-antibodies-causing-graves-disease-analytical-and-clinical-evaluation
#13
C U Frank, S Braeth, J W Dietrich, D Wanjura, U Loos
Graves' disease is caused by stimulating autoantibodies against the thyrotropin receptor inducing uncontrolled overproduction of thyroid hormones. A Bridge Assay is presented for direct detection of these thyroid-stimulating immunoglobulins using thyrotropin receptor chimeras. A capture receptor, formed by replacing aa residues 261-370 of the human thyrotropin receptor with residues 261-329 from rat lutropin/choriogonadotropin receptor and fixed to microtiter plates, binds one arm of the autoantibody. The second arm bridges to the signal receptor constructed from thyrotropin receptor (aa 21-261) and secretory alkaline phosphatase (aa 1-519) inducing chemiluminescence...
November 2015: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/26027253/-the-dynamics-of-hormonal-indicators-in-women-of-arkhangelsk-under-stimulation-of-corticotropine
#14
E V Tipisova, L P Poskotinova, I V Dvoriashina, E V Vereschiagina, N B Poliarush, A V Vilegjanina, A N Zolkina
The test with pharmaceutical "Synachten Depot", a synthetic analogue of corticotropine was carried out. The sampling consisted of 30 clinically healthy women aged from 20 to 30 years and residents of Arkhangelsk. The scheme of blood sampling provided basal sample, 30 and 60 minutes, I and 4 days after administration of pharmaceutical. After 30 minutes of testing, increase of level of cortisol (F), progesterone (Δ4 = p), testosterone, triiodothyronine (T3) and decreasing of level of insulin and follitropin were established After 60 minutes of testing maximal level of cortisol, high concentration of progesterone and triiodothyronine, increasing of levels of testosterone, estradiol and insulin and decrease of concentration of thyrotropin and prolactin were observed...
February 2015: Klinicheskaia Laboratornaia Diagnostika
https://www.readbyqxmd.com/read/25761594/single-molecule-analyses-of-fully-functional-fluorescent-protein-tagged-follitropin-receptor-reveal-homodimerization-and-specific-heterodimerization-with-lutropin-receptor
#15
Joseph E Mazurkiewicz, Katharine Herrick-Davis, Margarida Barroso, Alfredo Ulloa-Aguirre, Barbara Lindau-Shepard, Richard M Thomas, James A Dias
We have previously shown that the carboxyl terminus (cT) of human follicle-stimulating hormone (FSH, follitropin) receptor (FSHR) is clipped before insertion into the plasma membrane. Surprisingly, several different constructs of FSHR fluorescent fusion proteins (FSHR-FPs) failed to traffic to the plasma membrane. Subsequently, we discovered that substituting the extreme cT of luteinizing hormone (LH) receptor (LHR) to create an FSHR-LHRcT chimera has no effect on FSHR functionality. Therefore, we used this approach to create an FSHR-LHRcT-FP fusion...
April 2015: Biology of Reproduction
https://www.readbyqxmd.com/read/25434310/alterations-in-gene-expression-during-sexual-differentiation-in-androgen-receptor-knockout-mice-induced-by-environmental-endocrine-disruptors
#16
Dehong Liu, Liping Shen, Yonglin Tao, Ying Kuang, Lei Cai, Dan Wang, Meiduo He, Xuebo Tong, Shuguang Zhou, Jie Sun, Chenchen Shi, Chunxiao Wang, Yi Wu
In the present study, we aimed to explore the effect of environmental endocrine disruptors (EEDs) on sexual differentiation in androgen receptor (AR)-/-, AR+/- and AR+/+ male mice. By using a Cre-loxP conditional knockout strategy, we generated AR knockout mice. By mating flox-AR female mice with AR-Cre male mice, the offspring male mice which were produced were examined. Mice not subjected to any type of intervention were used as the controls. Furthermore, male mice of different genotypes were selected and further divided into subgroups as follows: the control group, bisphenol A (BPA) group and the dibutyl phthalate [corrected] (DBP) group...
February 2015: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/25340405/influence-of-the-hinge-region-and-its-adjacent-domains-on-binding-and-signaling-patterns-of-the-thyrotropin-and-follitropin-receptor
#17
Jörg Schaarschmidt, Sandra Huth, René Meier, Ralf Paschke, Holger Jaeschke
Glycoprotein hormone receptors (GPHR) have a large extracellular domain (ECD) divided into the leucine rich repeat (LRR) domain for binding of the glycoprotein hormones and the hinge region (HinR), which connects the LRR domain with the transmembrane domain (TMD). Understanding of the activation mechanism of GPHRs is hindered by the unknown interaction of the ECD with the TMD and the structural changes upon ligand binding responsible for receptor activation. Recently, our group showed that the HinR of the thyrotropin receptor (TSHR) can be replaced by those of the follitropin (FSHR) and lutropin receptor (LHCGR) without effects on surface expression and hTSH signaling...
2014: PloS One
https://www.readbyqxmd.com/read/25286107/ghrelin-effects-expression-of-several-genes-associated-with-depression-like-behavior
#18
María Belén Poretti, Mathias Rask-Andersen, Praveen Kumar, Susana Rubiales de Barioglio, Marta Fiol de Cuneo, Helgi B Schiöth, Valeria Paola Carlini
Ghrelin (Ghr) is an orexigenic peptide that is being investigated for its potential role in development of anxiety-like behavior and modulation of depressive-like symptoms induced by bilateral olfactory bulbectomy (OB) in rodents. Olfactory bulbectomy is an animal model useful to study of depression and Ghr could be an alternative therapeutic tool in depression therapy. We studied the effects of intracerebroventricular (i.c.v.) Ghr administration on the expression of hypothalamic genes related to depression and mood (delta opioid receptor (DOR), mu opioid receptor (MOR) and kappa opioid receptor (KOR), lutropin-choriogonadotropic hormone receptor (LHCGR), serotonin transporter (SERT), interleukin 1 beta (IL-1b), vasopressin (AVP) and corticotrophin releasing hormone (CRH)) in OB animals, as well as changes in plasma levels of AVP, CRH and adenocorticotropic hormone (ACTH)...
January 2, 2015: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/25079470/insights-into-the-coexistence-of-two-mutations-in-the-same-lhcgr-gene-locus-causing-severe-leydig-cell-hypoplasia
#19
Anastasia P Athanasoulia, Günter K Stalla, Matthias K Auer
BACKGROUND: Leydig cell hypoplasia is a rare autosomal recessive condition that interferes with the normal development of male external genitalia in 46,XY individuals. It is mediated by mutations in the lutropin/choriogonadotropin receptor gene, resulting in the impairment of either the binding of hormone or signal transduction. OBJECTIVE/DESIGN: We report a 32-year-old female patient with severe Leydig cell hypoplasia due to a novel homozygote nonsense mutation in exon 10 (c...
July 2014: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/24714837/gonadotropin-therapy-in-assisted-reproduction-an-evolutionary-perspective-from-biologics-to-biotech
#20
REVIEW
Rogério de Barros F Leão, Sandro C Esteves
Gonadotropin therapy plays an integral role in ovarian stimulation for infertility treatments. Efforts have been made over the last century to improve gonadotropin preparations. Undoubtedly, current gonadotropins have better quality and safety profiles as well as clinical efficacy than earlier ones. A major achievement has been introducing recombinant technology in the manufacturing processes for follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Recombinant gonadotropins are purer than urine-derived gonadotropins, and incorporating vial filling by mass virtually eliminated batch-to-batch variations and enabled accurate dosing...
2014: Clinics
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