Endocrine Abstracts

11beta-hydroxysteroid dehydrogenase type 1 (11B-HSD1) catalyses the inter-conversion of cortisone and cortisol, and has been implicated in the pathogenesis of a number of disorders including insulin resistance and obesity. The enzyme is a glycosylated membrane-bound protein, located in the lumen of the endoplasmic reticulum (ER) and has proved difficult to purify in an active state. Previously, we reported the successful expression and purification of human 11B-HSD1 from E. co...

Dehydroepiandrosterone (DHEA) is the crucial androgen precursor and hyperandrogenaemia is a major feature in Polycystic Ovary Syndrome (PCOS). DHEA sulfate (DHEAS) is generated from DHEA by DHEA sulfotransferase (SULT2A1) activity. The conversion of DHEAS to DHEA by steroid sulfatase has been reported to be of minor significance in human adults and only desulfated DHEA can be converted toward androgens. Therefore, SULT2A1 activity represents the rate-limiting step regulating t...

Recently, evidence has emerged that active 1,25dihydroxyvitamin D3 (1,25D3) is involved in modulating the immune response. Additionally, vitamin D3 insufficiency has been proposed as a predisposing factor for autoimmune diseases, which correlate with circulating inactive 25-hydroxyvitamin D3 (25D3). Substrate 25D3 is converted to 1,25D3 by the activating enzyme 1alpha-hydroxylase. We and others have p...

The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor (MR) 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 analysed renal 11b...

Studies in rats suggest that androgens are involved in sex-specific differences in blood pressure. In human studies there is no difference in blood pressure between boys and girls, but following puberty, men present with a higher blood pressure than women. Modulation of sodium reabsorption through the ENaC is an important component in the control of sodium balance. This is clearly demonstrated by rare genetic disorders of sodium-channel activity (Liddle's syndrome and pseudohy...

The crucial role of vitamin D in mineral homeostasis is well known. However recent evidence has documented its importance for immunomodulation and inflammation. The kidney is the main source for the endocrine synthesis of the active metabolite 1,25-dihdroxyvitamin D3 (1,25D3), with expression of the key enzyme, 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-OHase). Our aim was to investigate the alteration of the vitamin D hormonal system in renal failure and assess the impact...

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...