Endocrine Abstracts

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activates cortisol (F) from cortisone (E). Our recent human studies identified 11beta-HSD1 to the non-pigmented layer (NPE) of the ocular ciliary epithelium, confirming that this enzyme is integral to the physiology of aqueous humour (AH) production vital for the maintenance of intraocular pressure (IOP). 11beta-HSD1 has also been implicated in the pathogenesis of obesity, and our previous data have defined this enzyme i...

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain, which then drains principally into the dural sinuses. The balance between production and drainage, in part, facilitates a normal intracranial pressure. The secretion of sodium and anions by the CP, creates an osmotic gradient driving the movement of water into the ventricles. This mechanism is analogous to that found in the ocular ciliary ep...

The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor by inactivating cortisol. Evidence suggests impaired 11beta-HSD2 activity in some patients with hypertension but also in patients with renal disease where it may contribute to sodium retention, oedema and hypertension. To date these studies have relied upon urinary cortisol metabolite analyses as markers of renal 11beta-HSD2 activity.We have directly a...

The functions of dendritic cells (DCs) are tightly regulated such that protective immune responses are elicited and unwanted immune responses are prevented. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been identified as a major factor that inhibits the differentiation and maturation of DCs, an effect dependent upon its binding to the nuclear vitamin D receptor (VDR). Physiological control of 1,25(OH)2D3 levels is dependent upon the enzyme 25-hydroxyvitamin-D3-1alpha-hydroxylase...

Studies in vitro have highlighted the potent anti-cancer effects of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3). However, the in vivo application of 1,25D3 and its synthetic analogs remains problematical due to persistent hypercalcaemic side-effects. Recent studies have shown that it may be possible to overcome this in an autocrine fashion via extra-renal synthesis of 1,25D3. In particular, analysis of prostate and co...

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is synthesised by the enzyme 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-hydroxylase). The principal site of 1alpha-hydroxylase activity is in the proximal tubule of the kidney. In order to investigate renal vitamin D metabolism we have used a human proximal tubule cell line, HKC-8. We have previously shown that synthesis of 1,25D3 activity in these cells is sensitive to the concentration of calcium and North...

Sodium transport across the human ocular non-pigmented ciliary epithelium (NPE) is fundamental to the production aqueous humour and maintenance of intraocular pressure. In sodium transporting tissues, serum and glucocorticoid regulated kinase isoform 1 (SGK1) has been identified as an early corticosteroid target gene in the activation of pre-existing epithelial sodium channels (ENaC). We previously demonstrated the presence of both the mineralocorticoid (MR) and glucocorticoid...

Background: Women with PCOS experience higher rates of depression and anxiety. There is a paucity of research relating to perinatal mental health in women with PCOS, as well as a lack of evidence-based guidelines for assessment and management of mental disorders specific to pregnant women with PCOS. Limited available evidence suggests PCOS is associated with a higher prevalence of perinatal mental health disorders. However, perinatal guidelines currently do no...

Background: Adrenal cortical carcinoma (ACC) in children is a rare and aggressive disease. Further characterisation of the presenting features and biochemical markers are needed to support earlier diagnosis. Refractory hypertension related to high cortisol concentrations at presentation, and post-operative decrease in cortisol can be challenging to manage. Focus on endocrine management has not been previously described.Case Series: 34 patients (age 2 wee...

Objectives: Current provocative tests for GH deficiency (GHD) are neither 100% sensitive nor specific. GH neurosecretory dysfunction (NSD) refers to the presence of growth failure, normal stimulated GH responses, but impaired spontaneous GH secretion. We describe our experience in managing GHNSD over 7 years.Methods: We retrospectively reviewed a cohort of 106 children admitted for 12-h overnight GH profiles (with 20-min sampling) between 2010 and 2016. ...