Endocrine Abstracts

Background/objective: Published data suggest that growth hormone replacement (GHR) may be safely given to patients with hypopituitarism consequent upon a pituitary/peri-pituitary tumour. However, to date, these series have included a preponderance of patients treated with external pituitary irradiation. We have performed a retrospective study to evaluate the recurrence rate in a group of patients with pituitary/peripituitary tumours treated with GHR.Meth...

7-Oxysterols modulate lipid transport and promote oxidative stress and apoptosis in the vascular wall. 7-Ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOHC) are inter-converted by 11β-hydroxysteroid dehydrogenase-1 (11βHSD1), better known for metabolising glucocorticoids. Pharmacological inhibition of 11βHSD1 protects against atherosclerosis and these beneficial effects may be mediated through changes in glucocorticoids or oxysterols. To establish ...

The pre-receptor regulation of glucocorticoids is mediated by 11β-hydroxysteroid dehydrogenases (11β-HSD). The type 1 isoform is primarily responsible for the generation of active cortisol in tissues such as liver and adipose, whereas 11β-HSD2 regulates sodium and ion transport. Recently, we have shown the presence of functional 11β-HSD1 in the ciliary body of the eye where it is important in control of sodium transport, aqueous humour production and intrao...

Microsomal glucose-6-phosphatase (G6Pase) and glucose-6-phosphate transporter (G6PT) are key enzymes in regulation of blood glucose concentration. Deficiency of G6Pase gives rise to glycogen storage disease type Ia (GSDIa) whilst mutations in G6PT cause GSDIb. Both are characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly. G6Pase shares its substrate (G6P) with hexose-6-phosphate-dehydrogenase (H6PDH), an ER enzyme functionally coupled with, and which c...

Hypopituitarism is associated with profound androgen deficiency, even in patients who are adrenocorticotrophic hormone (ACTH) replete. DHEA has been shown to have a beneficial effect on well-being in patients with adrenal failure. We hypothesised that DHEA may be additive to the known effects of GH on psychological well-being in patients with hypopituitarism. In a double blind placebo controlled trial 50 mg DHEA or placebo was added to standard replacement, including growth ho...

We have recently identified inactivating mutations in the electron donor enzyme P450 oxidoreductase as the cause of disease in patients with apparent combined P450c17 and P450c21 deficiency, a variant of congenital adrenal hyperplasia (CAH) (1). Additionally, we suggested that P450 oxidoreductase deficiency (ORD) reveals the existence of an alternative pathway in human androgen synthesis present in fetal life only, explaining the concurrent presence of low circulating androgen...

Metabolic Syndrome (visceral obesity, insulin resistance, type2 diabetes) resembles Cushing's syndrome, but lacks elevated circulating cortisol levels. This has engendered the hypothesis that excessive local glucocorticoid regeneration, resulting from elevated adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) underlies the Metabolic Syndrome. We report that 11beta-HSD-1 nullizygosity (11beta-HSD-1-/-) reduced intra-adipose corticosterone levels and i...

Mutations in the HSD11B2 gene explain the syndrome of apparent mineralocorticoid excess (AME), which is characterised by severe hypokalaemic hypertension. Cortisol acts as a mineralocorticoid through failure of its inactivation to cortisone by 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). Patients are diagnosed by a raised THF+allo-THF/THE ratio. To date, approximately 30 mutations have been described in HSD11B2. Recently, three apparently unrelated kindreds with A...

BACKGROUND: Cell cycle dysregulation is one of the defining features of cancer. Cyclin-dependent kinase 4 (CDK4), together with its regulatory subunit Cyclin D, governs cell cycle progression in G1 phase. CDK4 is in turn regulated by cyclin-dependent kinase inhibitors, including p16INK4A (CDKN2A). Dysregulation of the INK4A/CDK4/cyclin D complex has been established in different a variety of types of human tumours. Dominant mutations affecting codon 24 of the CDK4 gene (replac...

Mutations in the HSD11B2 gene explain the syndrome of apparent mineralocorticoid excess (AME), which is characterised by severe hypokalemic hypertension. The enzyme product of the HSD11B2 gene, 11-beta hydroxysteroid dehydrogenase type 2 (11beta HSD2), converts cortisol to its inactive form, cortisone. This reaction occurs primarily in the kidney, preventing the mineralocorticoid effects of cortisol, and in the placenta where it is believed to regulate fetal growth by protecti...