Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge their ligand regulation or structure is available1–3. Here we report that glucocorticoid stress hormones activate adhesion receptor G3 (ADGRG3; also known as GPR97)4–6, prototypical GPCR. The cryo-electron microscopy structures GPR97–Go complexes bound to the anti-inflammatory drug beclomethasone ste...

Glucocorticoid-binding macromolecules were examined in Morris hepatomas 7787, 5123tc, 3683F, 7800, and 3683 and the Reuber hepatoma H-35 with the use of the synthetic glucocorticoid, triamcinolone acetonide. The physical properties of the triamcinolone acetonide-binding macromolecules of the hepatomas indicate that they are specific glucocorticoid receptors. The equilibrium association constant...

Corticosteroids are the most effective anti-inflammatory therapy for asthma. Inflammation in asthma is characterised by the increased expression of multiple inflammatory genes regulated by pro-inflammatory transcription factors, such as nuclear factor-kB and activator protein-1, which bind to and activate coactivator molecules that acetylate core histones and switch on gene transcription. Corti...

Chronic excessive activation of glucocorticoid receptors induces obesity, insulin resistance, glucose intolerance, dyslipidaemia and hypertension. Subtle abnormalities of the hypothalamic-pituitary-adrenal axis and/or of tissue sensitivity to glucocorticoids are also associated with these cardiovascular risk factors in patients with the metabolic syndrome. Furthermore, glucocorticoids have dire...

Corticosteroids - secreted after stress - have profound effects on brain and behavior. These effects are mediated by mineralocorticoid and glucocorticoid receptors, which are abundantly expressed in limbic neurons. The role of mineralocorticoid receptors in higher brain functions has never been well understood. Here we argue that the recently discovered low-affinity membrane version of the mine...

The aged rat shows a decline in hippocampal corticosterone receptors and dysfunction in learning and adrenocortical physiology previously linked to glucocorticoid effects upon the hippocampus. The Brattleboro rat, congenitally lacking vasopressin, also has a low number of hippocampal glucocorticoid receptors, as well as learning and endocrine impairments similar to those seen in the aged. Centr...

The steroid hormone receptors regulate important physiological functions such as reproduction, metabolism, immunity, and electrolyte balance. Mutations within steroid receptors result in endocrine disorders and can often drive cancer formation and progression. Despite the conserved three-dimensional structure shared among members of the steroid receptor family and their overlapping DNA binding ...

In this report, we demonstrate that, in contrast to most previously characterized nuclear receptors, hERR1 and hERR2 (human estrogen receptor-related protein 1 and -2) are constitutive activators of the classic estrogen response element (ERE) as well as the palindromic thyroid hormone response element (TRE(pal)) but not the glucocorticoid response element (GRE). This intrinsically activated sta...

In response to a stressor, physiological changes are set into motion to help an individual cope with the stressor. However, chronic activation of these stress responses, which include the hypothalamic–pituitary–adrenal axis and the sympathetic–adrenal–medullary axis, results in chronic production of glucocorticoid hormones and catecholamines. Glucocorticoid receptors expressed on a variety of i...

This narrative review demonstrates the close connection between impact of traumas experienced across generations, added to an environment unpredictability during organism’s life history. The effects trauma can be passed on subsequent generations through epigenetic mechanisms and changes in stress response axis, sensitivity glucocorticoid receptors, cortisol release. When associated, they form a...