Efficient eukaryotic expression system for authentic human sex hormone-binding globulin

2001 ◽  
Vol 360 (3) ◽  
pp. 609-615 ◽  
Author(s):  
Jan HILPERT ◽  
Henrik VORUM ◽  
Regina BURMEISTER ◽  
Robert SPOELGEN ◽  
Irina GRISHKOVSKAYA ◽  
...  

Sex hormone-binding globulin (SHBG) is the main carrier for androgens and oestrogens in humans. It mediates the transport of steroid hormones in the circulation and testicular fluid, and regulates their bioavailability to steroid-responsive tissues. In addition, the protein interacts with membrane receptors expressed in target tissues. Binding to the receptors is suspected to facilitate the uptake of steroid hormones and/or elicit cellular signal transduction. The identity of the SHBG receptor has not yet been resolved, in part due to a lack of sufficient quantities of authentic SHBG for receptor purification and molecular characterization. We have successfully addressed this problem by establishing an episomal expression system in human embryonic kidney cells that produces 5mg of fully active human SHBG per litre. The recombinant protein resembles native SHBG in terms of structure, glycosylation pattern and steroid-binding activity. Moreover, the protein interacts with plasma membranes in steroid target tissues, an activity not observed with SHBG from other recombinant expression systems. Thus our studies have removed an important obstacle to the further elucidation of the role SHBG plays in steroid hormone action.

2001 ◽  
Vol 360 (3) ◽  
pp. 609 ◽  
Author(s):  
Jan HILPERT ◽  
Henrik VORUM ◽  
Regina BURMEISTER ◽  
Robert SPOELGEN ◽  
Irina GRISHKOVSKAYA ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Carla Basualto-Alarcón ◽  
Paola Llanos ◽  
Gerardo García-Rivas ◽  
Mayarling Francisca Troncoso ◽  
Daniel Lagos ◽  
...  

In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.


Author(s):  
Catherine Duggan ◽  
Jean de Dieu Tapsoba ◽  
Frank Stanczyk ◽  
Ching-Yun Wang ◽  
Karen Foster Schubert ◽  
...  

2020 ◽  
Vol 8 (3) ◽  
Author(s):  
Thomaz Talarico Neto ◽  
Higino Carlos Hahns Júnior ◽  
Maria Clara Santos Minelli ◽  
José Mauricio Magraner Paixão dos Santos ◽  
Marcos Corrêa Junior ◽  
...  

Background: Military police training should characterize the necessary abilities to conduct their activities with excellence. Biochemical parameters have a significant role in the performance of individuals and, therefore, are of crucial importance when trying to improve the teamwork of police officers, particularly for special operations groups. Hence, the use of laboratory analysis in activities that cause great physiological stress is of paramount importance. Objectives: The present study aimed to evaluate the profile of steroid hormones and the sex hormone-binding-globulin of soldiers belonging to a special operations force. Methods: In this cross-sectional study, blood samples of 75 volunteers collected after 12 hours of fasting are analyzed. Data were analyzed using descriptive statistics (i.e., mean and standard deviation) and compared to the reference values for each biomarker, referencing each individual in their age group. Results: Most of the participants presented adequate concentrations for their respective ages in relation to the data analyzed. Even the inclusion of individuals from different age groups did not change the good results found in the group. Conclusions: The positive results found in such a heterogeneous group with respect to age group can be attributed to an extremely rigorous selection process and a training program that elevates them to the rank of elite soldiers of the military police.


1995 ◽  
Vol 132 (5) ◽  
pp. 594-598 ◽  
Author(s):  
Sonia C Dumoulin ◽  
Bertrand P Perret ◽  
Antoine P Bennet ◽  
Philippe J Caron

Dumoulin SC, Perret BP, Bennet AP, Caron PJ. Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone-binding globulin and corticosteroid-binding globulin) in humans. Eur J Endocrinol 1995;132:594–8. ISSN 0804–4643 Sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) levels were evaluated in euthyroid (N = 111), hyper- (N = 58) and hypothyroid (N = 38) men, in pre- and postmenopausal women (study 1) and in hyper- (N = 24) and hypothyroid (N = 15) patients before and after treatment with carbimazole or levothyroxine therapy (study 2). The SHBG levels are increased in hyper- and decreased in hypothyroid patients, whereas CBG levels are increased in hypo- and decreased in hyperthyroid patients. The SHBG levels are higher in women than in men with similar thyroid status. Plasma SHBG levels are correlated positively whereas CBG levels are correlated negatively with free thyroid hormone concentrations in men as well as women. In hypothyroid patients, SHBG concentrations increased (p < 0.01) and CBG concentrations decreased (p < 0.01) during levothyroxine treatment. In hyperthyroid patients, SHBG concentrations decreased (p < 0.01) and CBG concentrations increased (p < 0.01) during antithyroid treatment. The SHBG and CBG concentrations in treated hypo- and hyperthyroid patients were not significantly different from those of euthyroid controls. Our data indicate that SHBG and CBG levels depend on thyroid status. Corticosteroid-binding globulin is an index of thyroid hormone action at the liver level whose changes are opposite to those of SHBG in hyper- and hypothyroidism. Philippe Caron, Service d'Endocrinologie et Maladies Métaboliques, CHU Rangueil, 1 Avenue J Poulhès, 31054 Toulouse Cedex, France


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