Glucocorticoid pathway

The major androgen or androgen precursor produced by the adrenal cortex is dehydroepiandrosterone (DHEA). Most 17-hydroxypregnenolone follows the glucocorticoid pathway, but a small fraction is subjected to oxidative fission and removal of the two-carbon side chain through the action of 17,20-lyase. The lyase activity is actually part of the same enzyme (P450cl7) that catalyzes 17tt-hydroxylation. This is therefore a dual function protein. The lyase activity is important in both the adrenals and... 

The zona glomerulosa also secretes 18-hydroxy-corticosterone, a precursor steroid in the aldosterone biosynthetic pathway. This steroid also has mineralocorticoid properties, but is usually present in the circulation in extremely low concentrations. Mineralocorticoids are also synthesized in the zona fasciculata DOC is the most potent, but corticosterone and cortisol also have weak mineralo-corticoid activity. All of these steroids are synthesized as products of the glucocorticoid pathway. 

The glucocorticoid pathway is confined to the zona fasciculata of the adrenal cortex and it is catalyzed by the same CYP21 enzyme that is involved in the mineralocorticoid pathway in this zone along with CYPl IBl. The principal difference between the two pathways in the zona fasciculata is the initial substrate, and this explains... 

Xing, N. et al. (2002) Distinctive dendritic cell modulation by vitamin D3 and glucocorticoid pathways. Biochemical and Biophysical Research Communications,... 

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes a critical reaction in gluconeogenesis, which under many conditions is the rate-limiting step in the pathway. A cAlVfP response element (CRE) and a glucocorticoid response element (GRE) are each located upstream from the transcription start site. 

Schmidt P, Holsboer F, Spengler D (2001) Beta(2)-adrenergic receptors potentiate glucocorticoid receptor transactivation via G protein beta gamma-subimits and the phospho-inositide 3-kinase pathway. Mol Endocrinol 15 553-564 Schramm NL, McDonald MP, Limbird LE (2001) The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety. J Neurosci 21 4875-4882... 

In some species (eg, the rat), corticosterone is the major glucocorticoid. It is less firmly bound to protein and therefore metabolized more rapidly. The pathways of its degradation are similar to those of cortisol. 

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