Endocrine Abstracts

Steroid bioavailability is delineated by the “free hormone hypothesis” and its underlying tenet that only steroids not bound by plasma proteins enter cells. Steroid hormones, as well as their unconjugated precursors and metabolites, circulate bound by several unrelated plasma proteins, including albumin, orosomucoid, sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG), while the more water soluble sulphated steroid conjugates are bound large...

Upon their release from the steroidogenic cells of the adrenals, gonads and placenta, biologically active steroids are sequestered and transported in the blood bound by several proteins, including albumin, sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG). Together they also regulate the non-protein bound or ‘free’ fractions of steroid hormones in the blood and therefore control their ability to exit the blood circulation and enter target ...

Dr Hammond obtained his BSc from the University College of North Wales. After obtaining an MSc in Steroid Endocrinology from the University of Leeds in 1974, he continued postgraduate work in Biochemistry at the University of Oulu, Finland, and received his PhD in 1978. After postdoctoral training at the University of California San Francisco, Dr Hammond was appointed as an MRC (UK) Research Fellow at the University o...

Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood and is a serine protease inhibitor family member. Plasma CBG has a reactive center loop (RCL) structure that when cleaved by specific proteases, including neutrophil elastase, results in a loss of high affinity steroid-binding activity. Measurements of CBG levels are typically based on functional assays of its steroid-binding capacity or immunoassays, including enzyme-linked immunosorbant assays (ELISAs)...

Adipose exposure to glucocorticoids (GCs) results in visceral adiposity and insulin resistance. Only the unbound, free fraction of GC can diffuse into cells. Corticosteroid binding globulin (CBG) is the major GC carrier, binding 80–85% of circulating GCs with high affinity. Targeted proteolysis of CBG by neutrophil elastase (NE) significantly reduces CBG binding affinity. This suggests that neutrophil-mediated inflammation provides a regulatory mechanism for delivery of G...

Adipose exposure to glucocorticoids (GCs) results in visceral adiposity and insulin resistance. Only the unbound, free fraction of GC can diffuse into cells. Corticosteroid binding globulin (CBG) is the major GC carrier, binding 80–85% of circulating GCs with high affinity. Targeted proteolysis of CBG by neutrophil elastase (NE) significantly reduces CBG binding affinity. This suggests that neutrophil-mediated inflammation provides a regulatory mechanism for delivery of G...

Background: Corticosteroid-binding globulin (CBG) plays a critical role in regulating glucocorticoid bioavailability. During inflammation, plasma CBG behaves as an acute phase “negative” protein due to the down-regulation of hepatic SerpinA6 (Cbg) expression and proteolytic cleavage of CBG. CBG contains a protease-cleavage domain (RCL) that promotes the release of CBG-bound steroids at sites of inflammation. Using an established adjuvant induced art...

Many organs are functionally sexually dimorphic, resulting in profound differences in the activity of several physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The rodent HPA axis matures post-weaning, characterized by parallel increments in adrenal weight, adrenal cortical size and corticosterone secretion. Between postnatal days (PND) 30 to 45, these parameters increase to a greater extent in females compared to males. Over this same interval, h...

Sex hormone-binding globulin (SHBG) carries sex steroids in blood regulating their bioavailability. Red wine consumption increases plasma SHBG levels, and we have discovered that resveratrol, a polyphenol enriched in red wine, acts specifically through the human constitutive androstane receptor (CAR), a drug/xenobiotic detoxification gene regulator, to increase hepatic SHBG production. Chromatin immunoprecipitation and luciferase reporter gene assays show that human CAR binds ...

Sex Hormone binding globulin (SHBG) is a plasma steroid binding protein that is the major determinant androgen and estrogen access to target tissues. Several ligands of SHBG have been predicted by computational methods or discovered through basic research, they include pharmaceutical, natural plant extracts and anthropogenic endocrine disrupting compounds. In this study we characterized 3,4-Divanillyltetrahydrofuran (DVT), a non-steroidal ligand of SHBG, and Danazol, a synthet...