Influence of sex hormone binding globulin and serum albumin on the conversion of androstenedione to testosterone by human erythrocytes

Abstract. The influence of human serum albumin and sex hormone binding globulin (SHBG) on the enzymic conversion of androstenedione to testosterone in human erythrocytes was investigated in vitro. Total plasma and albumin delayed the conversion rate of androstenedione, while SHBG increased it markedly. The effect of SHBG was largely abolished by heating to 60°C for 1 h and by saturating its binding sites by DHT. The effect of both proteins was found to be related to their concentration. It appears that the binding sites of albumin provide a mechanism for retarding androstenedione uptake by the erythrocytes and that the high binding affinity of SHBG for testosterone facilitates the diffusion of this steroid out of the cell and thus, displaces the chemical equilibrium within the cell.

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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

Clinical Science ◽

10.1042/cs0640307 ◽

1983 ◽

Vol 64 (3) ◽

pp. 307-314 ◽

Cited By ~ 29

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.

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Analysis of Hormone–Protein Binding in Solution by Ultrafast Affinity Extraction: Interactions of Testosterone with Human Serum Albumin and Sex Hormone Binding Globulin

Analytical Chemistry ◽

10.1021/acs.analchem.5b03007 ◽

2015 ◽

Vol 87 (22) ◽

pp. 11187-11194 ◽

Cited By ~ 15

Author(s):

Xiwei Zheng ◽

Cong Bi ◽

Marissa Brooks ◽

David S. Hage

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Protein Binding ◽

Human Serum ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

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Identifying Steroid Hormone Binding Sites on Human Serum Albumin by 2D NMR

Biophysical Journal ◽

10.1016/j.bpj.2012.11.2392 ◽

2013 ◽

Vol 104 (2) ◽

pp. 430a ◽

Cited By ~ 1

Author(s):

Eileen S. Krenzel ◽

Heidi A. Schwanz ◽

Ravi Jasu ◽

Michael Zakharov ◽

Shalendar Bhasin ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Binding Sites ◽

Steroid Hormone ◽

2D Nmr ◽

Hormone Binding

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Regulation of Sex-Hormone-Binding Globulin Production by Endogenous Estrogens in Vitro

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1995.1127 ◽

1995 ◽

Vol 206 (3) ◽

pp. 895-901 ◽

Cited By ~ 12

Author(s):

M. Loukovaara ◽

M. Carson ◽

H. Adlercreutz

Keyword(s):

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

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Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages

Mediators of Inflammation ◽

10.1155/2018/3062319 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 9

Author(s):

Hiroki Yamazaki ◽

Akifumi Kushiyama ◽

Hideyuki Sakoda ◽

Midori Fujishiro ◽

Takeshi Yamamotoya ◽

...

Keyword(s):

Metabolic Syndrome ◽

Protective Effect ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding ◽

Lipid Degradation ◽

Protein Levels ◽

Anti Inflammatory ◽

20 Nm

Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for metabolic syndrome including diabetes, obesity, and cardiovascular events. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, using adipocytes and macrophages, we focused on the in vitro effects of SHBG on inflammation as well as lipid metabolism. Incubation with 20 nM SHBG markedly suppressed lipopolysaccharide- (LPS-) induced inflammatory cytokines, such as MCP-1, TNFα, and IL-6 in adipocytes and macrophages, along with phosphorylations of JNK and ERK. Anti-inflammatory effects were also observed in 3T3-L1 adipocytes cocultured with LPS-stimulated macrophages. In addition, SHBG treatment for 18 hrs or longer significantly induced the lipid degradation of differentiated 3T3-L1 cells, with alterations in its corresponding gene and protein levels. Notably, these effects of SHBG were not altered by coaddition of large amounts of testosterone or estradiol. In conclusion, SHBG suppresses inflammation and lipid accumulation in macrophages and adipocytes, which might be among the mechanisms underlying the protective effect of SHBG, that is, its actions which reduce the incidence of metabolic syndrome.

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