Steroid hormones pathway

Because steroids are lipophilic, they diffuse easily through the cell membranes, and therefore have a very large distribution volume. In their target tissues, steroids are concentrated by an uptake mechanism which relies on their binding to intracellular proteins (or " receptors ", see below). High concentration of steroids are also found in adipose tissue, although this is not a target for hormone action. In the human male, adipose tissue contains aromatase activity, and seems to be the main source of androgen-derived estrogens found in the circulation. But most of the peripheral metabolism occurs in the liver and to some extent in the kidneys, which are the major sites of hormone inactivation and elimination, or catabolism (see below).

Because non-genomic pathways include any mechanism that is not a genomic effect, there are various non-genomic pathways. However, all of these pathways are mediated by some type of steroid hormone receptor found at the plasma membrane. [13] Ion channels, transporters, G-protein coupled receptors (GPCR), and membrane fluidity have all been shown to be affected by steroid hormones. [9] Of these, GPCR linked proteins are the most more information on these proteins and pathways, visit the steroid hormone receptor page.

Cells of the zona fasciculata and zona reticularis lack aldosterone synthase (CYP11B2) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone. However, both these zones do contain the CYP17A1 missing in zona glomerulosa and thus produce the major glucocorticoid, cortisol. Zona fasciculata and zona reticularis cells also contain CYP17A1, whose 17,20-lyase activity is responsible for producing the androgens, dehydroepiandosterone (DHEA) and androstenedione. Thus, fasciculata and reticularis cells can make corticosteroids and the adrenal androgens, but not aldosterone.

Figure 1. Steroid hormones (., estrogen, androgen, progesterone) travel through the bloodstream from an endocrine gland bound by a steroid binding protein (SBP). The steroid is released from the SBP and is transported across the extracellular membrane and into the cell where is binds a nuclear receptor (., ESR1, AR, PGR). The steroid also binds a heat shock protein (HSP90), a chaperone protein that aids in protein folding. HSP90 dissociates, and the steroid and nuclear receptor cross the nuclear membrane. The steroid and nuclear receptor homodimerize and bind to the hormone response element (HRE) within the promoter of a gene , which activates gene transcription and promotes cell growth and survival. Specific nodes in the pathway that are therapeutically actionable are noted. Click here to open a larger version of this image in a new window.

Steroid hormones pathway

steroid hormones pathway

Figure 1. Steroid hormones (., estrogen, androgen, progesterone) travel through the bloodstream from an endocrine gland bound by a steroid binding protein (SBP). The steroid is released from the SBP and is transported across the extracellular membrane and into the cell where is binds a nuclear receptor (., ESR1, AR, PGR). The steroid also binds a heat shock protein (HSP90), a chaperone protein that aids in protein folding. HSP90 dissociates, and the steroid and nuclear receptor cross the nuclear membrane. The steroid and nuclear receptor homodimerize and bind to the hormone response element (HRE) within the promoter of a gene , which activates gene transcription and promotes cell growth and survival. Specific nodes in the pathway that are therapeutically actionable are noted. Click here to open a larger version of this image in a new window.

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