Endocrine Abstracts

Delayed wound healing (WH), characterized by ischemia, is exacerbated by glucocorticoid (GC) excess. Local GC availability is regulated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which generates the GC cortisol from inactive cortisone. We previously reported improved WH in 11β-HSD1-null mice but regulation of 11β-HSD1 by hypoxia in human skin remains unknown. Primary human dermal fibroblasts (HDF, biological n=3), were treated...

Chronic wounds contribute significantly to patient morbidity, mortality and associated healthcare costs. Glucocorticoid (GC) excess and hypoxia are both associated with impaired wound healing (WH) outcomes. The cyclooxygerase 2 (COX2) pathway is an integral component of inflammation and WH. Locally, GC availability is regulated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which generates cortisol from inactive cortisone. Although we recently demon...

Cushing’s disease presents with multiple symptoms of systemic glucocorticoid (GC) excess including increased skin thinning and poor wound healing (WH). Local GC concentrations are regulated by 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes converting inactive cortisone/11-dehydrocorticosterone to cortisol/corticosterone (11β-HSD1) or vice versa (11β-HSD2). We previously demonstrated elevated 11β-HSD1 activity during early WH, hypothe...

UVB exposure induces skin damage including dermal atrophy, telangiectasia, fragility and poor wound healing; symptoms also attributable to glucocorticoid (GC) excess (e.g. Cushing’s syndrome). In peripheral tissues including skin, GC availability is regulated by 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1/2 which respectively activate/deactivate cortisol (and rodent corticosterone) from/to cortisone (and rodent 11-dehydrocorticosterone). Although we previ...

Glucocorticoid (GC) excess inhibits wound healing (WH) causing increased patient discomfort and infection risk. The GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates local GC availability in tissues including liver, adipose, and muscle. 11β-HSD1 is also expressed in skin, where studies recently demonstrated increased levels in older donors and a reversal of age-induced dermal atrophy in 11β-HSD1-null mice. However, the role o...

Glucocorticoid (GC) excess adversely affects many aspects of skin homeostasis, characteristics of which are also seen during ageing (e.g. poor wound healing). The mechanisms underlying this remain unclear. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates cortisol, independently of circulating concentrations, and we have previously demonstrated increased 11β-HSD1 expression in human dermal fibroblasts (HDF) from aged donors. We have now e...

Glucocorticoids are highly detrimental to skin integrity and function both when used locally for anti-inflammatory treatments and during conditions of raised systemic concentrations such as Cushing’s syndrome. Many of the adverse effects of glucocorticoids on skin are also symptoms associated with natural intrinsic aging and extrinsic photoaging.Locally, glucocorticoid availability is regulated independently of circulating levels by 11β-hydroxy...

Glucocorticoids (GC) drive multiple adverse effects in skin e.g. epidermal thinning, dermal atrophy and impaired wound healing (WH). Our previous findings indicate increased expression of the GC-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in primary human dermal fibroblasts (HDF), full-thickness skin from older donors and during the inflammatory phase of mouse skin WH. We also reported protection from age-induced dermal atrophy and improved W...

Glucocorticoid (GC) excess, whether exogenously- or endogenously-derived, induces many adverse effects in skin including thinning, decreased cellularity and reduced collagen synthesis. Consequently, skin exhibits reduced dermal structural integrity, increased atrophy/fragility/bruising and impaired wound healing, effects that perfectly mimic skin ageing. Local GC levels are regulated in a tissue-specific manner by 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes i...

Cortisol excess drives multiple adverse effects including hypertension, dyslipidemia, and delayed wound healing. Activation of cortisol by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has shown promise as a therapeutic target for these comorbidities but clinical progress has been hampered by variable 11β-HSD1 inhibitor efficacy. Transcriptomic profiling by RNA-seq found 611 11β-HSD1 target genes in primary skin fibroblasts (n = 3),...