Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening

Gnanasekar,

doi:10.3892/ijmm_00000248

Cited by 5 publications

(3 citation statements)

References 52 publications

(81 reference statements)

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“…For example, SHBG treatment led to Erk1/2 phosphorylation in HepG2 hepatocytes, which reduced levels of target mRNAs and proteins 69 . In addition, the incubation of cells with SHBG resulted in the accumulation of cyclic adenosine monophosphate (cAMP) as detected in cytotrophoblasts or in MCF-7 breast cancer cells, which could be further increased by the addition of steroid ligands 70,71 . E2-mediated non-genomic signaling via mER in leukocytes also involves the activation of these signaling pathways 72,73 .…”

Section: Discussionmentioning

confidence: 99%

Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor

Balogh

Kárpáti

Schneider

et al. 2019

Sci Rep

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The complex effects of estradiol on non-reproductive tissues/cells, including lymphoid tissues and immunocytes, have increasingly been explored. However, the role of sex hormone binding globulin (SHBG) in the regulation of these genomic and non-genomic actions of estradiol is controversial. Moreover, the expression of SHBG and its internalization by potential receptors, as well as the influence of SHBG on estradiol uptake and signaling in lymphocytes has remained unexplored. Here, we found that human and mouse T cells expressed SHBG intrinsically. In addition, B lymphoid cell lines as well as both primary B and T lymphocytes bound and internalized external SHBG, and the amount of plasma membrane-bound SHBG decreased in B cells of pregnant compared to non-pregnant women. As potential mediators of this process, SHBG receptor candidates expressed by lymphocytes were identified in silico, including estrogen receptor (ER) alpha. Furthermore, cell surface-bound SHBG was detected in close proximity to membrane ERs while highly colocalizing with lipid rafts. The SHBG-membrane ER interaction was found functional since SHBG promoted estradiol uptake by lymphocytes and subsequently influenced Erk1/2 phosphorylation. In conclusion, the SHBG-SHBG receptor-membrane ER complex participates in the rapid estradiol signaling in lymphocytes, and this pathway may be altered in B cells in pregnant women.

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Section: Discussionmentioning

confidence: 99%

Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor

Balogh

Kárpáti

Schneider

et al. 2019

Sci Rep

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“…Crystallographic analysis at 1.55Å showed important details of steroid-binding site and quaternary structure of the dimer [22]. Recent reports have associated SHBG with other important physiological rules associated to sexual receptivity and metabolic disorders such as diabetes and obesity [21,[23][24][25][26]. Among steroids bound to SHBG, we may highlight E2, which bind at dissociation constant in nanomolar range [27][28].…”

Section: Introductionmentioning

confidence: 86%

Aqueous solution interactions with sex hormone-binding globulin and estradiol: a theoretical investigation

Silva

Santos

2018

J Biol Phys

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Sex hormone-binding globulin (SHBG) is a binding protein that regulates the availability of steroid hormones in the plasma. Although best known as a steroid carrier, recent studies have associated SHBG in modulating behavioral aspects related to sexual receptivity. Among steroids, estradiol (17β-estradiol, oestradiol or E2), documented as the most active endogenous female hormone, exerts important physiological roles in both reproductive and non-reproductive functions. In this framework, we employed molecular dynamics (MD) and docking techniques for quantifying the interaction energy between a complex aqueous solution, composed by different salts, SHBG and E2. As glucose concentration resembles measured levels in diabetes, special emphasis was devoted to analyzing the interaction energy between this carbohydrate, SHBG and E2 molecules. The calculations revealed remarkable interaction energy between glucose and SHBG surface. Surprisingly, a movement of solute components toward SHBG was observed, yielding clusters surrounding the protein. The high energy and short distance between glucose and SHBG suggests a possible scenario in favor of a detainment state between the sugar and the protein. In this context, we found that glucose clustering does not insert modification on binding site area nor over binding energy SHBG-E2 complex, in spite of protein superficial area increment. The calculations also point to a more pronounced interaction between E2 and glucose, considering the hormone immersed in the solution. In summary, our findings contribute to a better comprehension of both SHBG and E2 interplay with aqueous solution components.

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“…In fact, it has been reported that 25–40% of pregnant women can be affected by RLS (Cesnik et al 2010). Moreover, recent studies have shown that Thy-1 forms a physical interaction with sex hormone-binding globulin (SHBG) (Gnanasekar et al 2009) and that SHBG is transported into brain cells in a sex hormone specific manner (Caldwell et al 2007). …”

Section: Introductionmentioning

confidence: 99%

Gender‐specific regulation of tyrosine hydroxylase in thymocyte differentiation antigen‐1 knockout mice

Carkaci-Salli¹,

Battula²,

Wang³

et al. 2012

J of Neuroscience Research

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THYmocyte differentiation antigen 1 (Thy-1), is a cell surface glycoprotein found on T cells and neurons and is involved in cell-to-cell interactions. In addition, Thy-1 knockouts (KO) are a potential mouse model of restless legs syndrome (RLS) based on clinical observations and the role of dopamine in the disease. In this study, we analyzed the activity and quantity of tyrosine hydroxylase (TH; the rate-limiting enzyme in dopamine production) and determined phosphorylation levels for the enzyme (phospho-serine-40 (pSer-40)). There was no significant difference in the total TH activity and pSer-40 TH levels between Thy-1 KO and control groups; however, TH specific activity was significantly lower (by 26%) in Thy-1 KO mice. This difference is, in part, due to increased TH protein levels in this group (increased by 29%). When analyzed by gender, we determined that Thy-1 KO female mice striata contained less TH specific activity compared to control females (decreased by 41%) and male control or Thy-1 KO animals (decreased by 30%). TH specific activity and pSer-40 TH levels between male Thy-1 KO and control displayed no differences. However, pSer-40 TH was significantly higher in control females (38%) compared to control or Thy-1 KO males. The Thy-1 KO females exhibited significantly lower (28%) pSer-40 TH (normalized to GAPDH or TH) than control females. Indeed, the Thy-1 KO females had 50% of the pSer-40 TH found in controls. Our results suggest a gender effect on TH specific activity, TH protein levels and serine-40 phosphorylation of TH in Thy-1 KO female mice.

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Identification of sex hormone binding globulin-interacting proteins in the brain using phage display screening

Cited by 5 publications

References 52 publications

Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor

Sex hormone-binding globulin provides a novel entry pathway for estradiol and influences subsequent signaling in lymphocytes via membrane receptor

Aqueous solution interactions with sex hormone-binding globulin and estradiol: a theoretical investigation

Gender‐specific regulation of tyrosine hydroxylase in thymocyte differentiation antigen‐1 knockout mice

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