Introduction The presence of corticosteroid-binding globulin (CBG) in plasma was detected about 30 yr ago, and of sex hormone-binding globulin (SHBG) about 20 yr ago. In the interval since their discovery, sophisticated binding and RIAs have been devised for their measurement; their concentrations in plasma and other biological fluids, from milk to saliva, have been measured in myriad clinical conditions in humans, and numerous experimental ones in animals; their phyletic distribution has been examined; they have been isolated and their complementary DNAs (cDNAs) cloned; their binding specificities for steroids have been examined in heroic detail; hormonal and drug influences on their plasma concentration in vivo, and their secretion by liver cells in vitro, have been widely explored; they have been the subject of two long, splendid monographs (1, 2) and many shorter reviews (3–11) [wherein the original citations for the first part of this sentence may be found]—and yet we still have not come to a consens...

The functions of corticosteroid-binding globulin and sex hormone-binding globulin: recent advances.

Perfluorooctane sulfonic acid (PFOS) accumulates in the liver and blood of exposed organisms. The potential for these surfactant molecules to interfere with hormone/protein interactions in blood is of concern given the importance of these interactions. The PFOS binding to serum proteins was investigated by assessing its ability to displace a variety of steroid hormones from specific binding proteins in the serum of birds and fishes. Perfluorooctane sulfonic acid had only a weak ability to displace estrogen or testosterone from carp serum steroid binding proteins. Displacement of cortisone in avian sera occurred at relatively low PFOS concentrations. Corticosterone displacement potency increased with chain length, and sulfonic acids were more potent than carboxylic acids. The PFOS concentrations estimated to cause these effects were 320 μM or greater, equivalent to serum concentrations greater than 160 mg/L. Using mass spectrometry and direct in vitro binding assays, PFOS was demonstrated to bind strongly to bovine serum albumin (BSA) in a 1:1 stoichiometric ratio. It appears that PFOS in serum is in general bound to albumins. Concentrations of PFOS required to saturate albumin would be in excess of 50 to 100 mg/L. Based on current environmental concentrations, it is unlikely that PFOS would cause displacement of hormones from serum proteins in wildlife.

Binding of perfluorinated fatty acids to serum proteins.

Stressors elicit a complex but variable suite of endocrine events. Comparative studies of the stress response have focused primarily on the adrenocortical response to stress, in particular the measurement of plasma levels of glucocorticoids. However, a number of other factors contribute to and modify cellular and organismal responses to glucocorticoids. Notably, plasma corticosteroid binding globulins (CBGs) can regulate the general availability of steroid to tissues, and/or direct the delivery of hormones to specific sites. In this paper, we discuss possible functions of CBG and mechanisms of CBG action, review CBG characteristics among vertebrates, and discuss our recent studies indicating that CBG may indeed modulate responses to stressors. For example, in house sparrows, we found that basal and stress-induced concentrations of total corticosteroid (cortisol or corticosterone) (CORT) vary seasonally, but CBG concentrations change proportionally, so that free CORT concentrations appear static year-round. In contrast, in white-crowned sparrows and tree lizards, CBG concentrations change under conditions when total CORT levels do not, resulting in significant changes in circulating free CORT. These differences in free CORT are masked if CBG is not accounted for. We have also found that the binding properties of CBG vary considerably between species and need to be determined empirically. Such studies led to the observation that CBG in several species may also serve as a functional androgen binding protein; this is especially important for birds, because previous studies had concluded that birds lack androgen binding globulins. We propose that consideration of CBG is paramount to understanding the role of glucocorticoids in mediating behavioral and physiological responses to stress.

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Plasma binding proteins as mediators of corticosteroid action in vertebrates

Measuring cortisol in human psychobiological studies.

The biology of transferrin.

A recognition system for sex-hormone-binding protein-estradiol complex in human decidual endometrium plasma membranes.

Interaction of human CBG with cell membranes.

Specific steroid-binding glycoproteins of human blood plasma: novel data on their structure and function.

Subcellular distribution and selectivity of the protein-binding component of the recognition system for sex-hormone-binding protein-estradiol complex in human decidual endometrium.

George V. Avvakumov

Papers

A recognition system for sex-hormone-binding protein-estradiol complex in human decidual endometrium plasma membranes.

Interaction of human CBG with cell membranes.

Specific steroid-binding glycoproteins of human blood plasma: novel data on their structure and function.

Subcellular distribution and selectivity of the protein-binding component of the recognition system for sex-hormone-binding protein-estradiol complex in human decidual endometrium.

Study of the carbohydrate moiety of human serum sex hormone-binding globulin