Photoaffinity Labeling of Human Sex Hormone-Binding Globulin Using 17α-Alkylamine Derivatives of 3β-Androstanediol Substituted with Azidonitrophenylamido, Azidonitrophenylamino, or Trifluoroazidonitrophenylamino Chromophores. Localization of Trp-84 in the Vicinity of the Steroid-Binding Site†

Biochemistry ◽  
2001 ◽  
Vol 40 (50) ◽  
pp. 15424-15435 ◽  
Author(s):  
Christophe Chambon ◽  
Djamila Bennat ◽  
Frédéric Delolme ◽  
Guy Dessalces ◽  
Thierry Blachère ◽  
...  
Keyword(s):  
Binding Site ◽  
Photoaffinity Labeling ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Steroid Binding ◽  
Derivatives Of

Resolution of a Disordered Region at the Entrance of the Human Sex Hormone-binding Globulin Steroid-binding Site

2002 ◽  
Vol 318 (3) ◽  
pp. 621-626 ◽  
Author(s):  
Irina Grishkovskaya ◽  
George V Avvakumov ◽  
Geoffrey L Hammond ◽  
Yves A Muller
Keyword(s):  
Binding Site ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Steroid Binding

Binding of Testosterone and Oestradiol to Sex Hormone Binding Globulin, Human Serum Albumin and other Plasma Proteins: Evidence for Non-Specific Binding of Oestradiol to Sex Hormone Binding Globulin

1983 ◽  
Vol 64 (3) ◽  
pp. 307-314 ◽  
Author(s):  
M. Jawed Iqbal ◽  
Maureen Dalton ◽  
Robert S. Sawers
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Binding Site ◽  
Plasma Proteins ◽  
Specific Binding ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Normal Female ◽  
Hormone Binding

1. The percentage binding of testosterone (T) and oestradiol (E2) to sex hormone binding globulin (SHBG) and human serum albumin (HSA) was determined over a range of SHBG concentrations of 16–250 nmol of dihydrotestosterone (DHT) bound/l. It was found that the binding of both T and E2 to HSA was a function of their binding to SHBG and bore an inverse relationship to it. After removal of both SHBG and HSA from plasma by affinity chromatography a ‘residual’ binding of about 11% for T and 12% for E2 was still apparent. in addition to the specific high-affinity, low capacity binding of E2 to SHBG, non-specific low-affinity binding of 7–12% was demonstrated after selective denaturation of the specific binding site of the latter. 2. Competition studies indicated that although at the relatively higher levels of SHBG found in the normal female the physiological concentrations of E2, T and DHT need not be taken into account in estimating the unbound fractions of steroids, at the relatively lower levels of SHBG found in normal men and hirsute women, the physiological concentrations of T and DHT are effective in causing statistically significant displacement of E2 from the common, specific binding site on SHBG. 3. A simple computerized technique is described for the determination of fractions of E2 and T respectively, that are unbound to SHBG, unbound to SHBG and HSA, and unbound to all plasma proteins, when the total plasma levels of E2, T, DHT and SHBG are known.

Resolution of the steroid-binding and dimerization domains of human sex hormone-binding globulin by expression in Escherichia coli

Biochemistry ◽  
1995 ◽  
Vol 34 (10) ◽  
pp. 3231-3238 ◽  
Author(s):  
Catherine Hildebrand ◽  
Wayne P. Bocchinfuso ◽  
David Dales ◽  
Geoffrey L. Hammond
Keyword(s):  
Escherichia Coli ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Expression In Escherichia Coli ◽  
Steroid Binding

scholarly journals Osteocalcin and Sex Hormone Binding Globulin Compete on a Specific Binding Site of GPRC6A

Endocrinology ◽  
2016 ◽  
Vol 157 (11) ◽  
pp. 4473-4486 ◽  
Author(s):  
Luca De Toni ◽  
Diego Guidolin ◽  
Vincenzo De Filippis ◽  
Simone Tescari ◽  
Giacomo Strapazzon ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Binding Site ◽  
Computational Modelling ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Dependent Manner ◽  
Hormone Binding ◽  
Human Embryonic Kidney ◽  
Molar Excess ◽  
293 Cells

The undercarboxylated form of osteocalcin (ucOC) regulates male fertility and energy metabolism, acting through the G protein-coupled receptor (GPRC)6A, thus forming a new pancreas-bone-testis axis. Recently, GPRC6A has also been suggested to mediate the nongenomic responses of free testosterone (T). However, these data did not consider the physiological scenario, where circulating T is mainly bound to sex hormone-binding globulin (SHBG) and only a small percentage circulates freely in the blood. Here, by the use of computational modelling, we document the existence of similar structural moieties between ucOC and SHBG that are predicted to bind to GPRC6A at docking analysis. This hypothesis of competition was assessed by binding experiments on human embryonic kidney-293 cells transfected with human GPRC6A gene. Unliganded SHBG specifically bound the membrane of human embryonic kidney-293 cells transfected with GPRC6A and was displaced by ucOC when coincubated at 100-fold molar excess. Furthermore, specific downstream Erk1/2 phosphorylation after stimulation of GPRC6A with ucOC was significantly blunted by 100-fold molar excess of unliganded SHBG. Intriguingly previous incubation with unliganded SHBG, followed by incubation with T, induced Erk1/2 phosphorylation in a dose-dependent manner. Neither binding nor stimulating activities were shown for SHBG saturated with T. Experiments on mutation constructs of GPRC6A strengthened the hypothesis of a common binding site of ucOC and SHBG. Given the role of GPRC6A on energy metabolism, these data agree with epidemiological association between SHBG levels and insulin sensitivity, suggest GPRC6A as a likely SHBG receptor, and add bases for the possible regulation of androgen activity in a nonsteroidal manner.

scholarly journals Resolution of the Human Sex Hormone-binding Globulin Dimer Interface and Evidence for Two Steroid-binding Sites per Homodimer

2001 ◽  
Vol 276 (37) ◽  
pp. 34453-34457 ◽  
Author(s):  
George V. Avvakumov ◽  
Irina Grishkovskaya ◽  
Yves A. Muller ◽  
Geoffrey L. Hammond
Keyword(s):  
Binding Sites ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Dimer Interface ◽  
Steroid Binding
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