Endocrine Abstracts

Objectives: To determine long-term functional outcome following traumatic brain injury (TBI) in childhood.Patients: Longitudinal study of 49 participants with TBI (21 mild, 28 moderate/severe TBI) and 16 healthy controls matched for age, gender and socioeconomic status. Age at TBI (median (range)) 11.8 (1–16) years; 17 were prepubertal, 16 peripubertal, 16 postpubertal. Age at study 19.7 (10–26) years, time post TBI 8.6 (5.8–10.8) years. A...

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...

Background: Increased childhood cancer survival has resulted in an accruing cohort faced with potential infertility. We have previously shown that sperm cryopreservation is acceptable to 70–80% of adolescents and testicular volume, LH and testosterone concentrations positively predict success in ~33% that bank. However, little is known about semen characteristics in relation to age and puberty. Here, we present data on our subcohort of 79 boys who produced a semen sample ...

Case history: A 51-year-old lady with a background of classical migraine and amenorrhoea conceived successfully via IVF, without prior endocrine assessment. Symptoms during the third trimester of pregnancy led to the diagnosis of a pituitary mass lesion (see Table). Possible differential diagnoses, on subsequent endocrine review, included macroprolactinoma, microprolactinoma with expansion during pregnancy, or lymphocytic hypophysitis.After 6 years of do...

Nearly all the functions of the liver display zonation in distribution within each the lobule. Hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1). Dysregulation of hepatic 11β-HSD1 activity has been implicated in insulin resistance. Key processes such as gluconeogenesis are located in the periportal hepatocytes, although current dogma describes hepatic 11&#94...

There is a growing body of literature indicating that circadian mechanisms regulate metabolism in adipose tissues. Genes encoding the core circadian regulatory proteins (CCRP) display a robust oscillatory expression profile in murine adipose tissue depots, as well as the bone, liver, and heart. Temporally restricted food access as well as photic stimuli can entrain the CCRP expression. In murine models, deletion or mutation of the CCRP genes, clock and PPAR gamma coa...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive glucocorticoid to their active form (cortisone to cortisol in humans, 11-dehydrocorticosterone (11-DHC) to corticosterone in mice), and is dependent upon the presence of cofactor NADPH generated by the enzyme hexose-6-phosphate (H6PDH) for its activity. The 11β-HSD1/H6PDH system is implicated in the pathogenesis of the metabolic syndrome by generating tissue specific glucocorticoid excess. The ...

6-Phosphogluconate dehydrogenase (6PGDH) is the third enzyme of the oxidative phase of the pentose phosphate pathway. The cytosolic form of this pathway is well characterised, but the details and significance of the endoplasmic reticulum (ER) version are only beginning to be understood. We have previously identified hexose-6-phosphate dehydrogenase (H6PDH), which catalyses the first two steps of this pathway within the lumen of the ER, as a pivotal regulator of ER reductases s...

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...

Type 2 diabetes manifests when pancreatic β-cells secrete inadequate insulin in response to elevated glucose. A known culprit in metabolic diseases is excessive exposure to glucocorticoids (GCs). GCs increase hepatic gluconeogenesis, decrease insulin sensitivity in skeletal muscle and adipose tissue and suppress the development of β-cells. In rodents, inactive GC 11-dehydrocorticosterone (A) is converted to active corticosterone (B) by the enzyme 11β-hydroxyster...