Endocrine Abstracts

5alpha-Reductase 1 (5aR1) catalyses A-ring reduction of glucocorticoids and androgens. We previously demonstrated that transgenic disruption of 5aR1 predisposes male mice to fatty liver and insulin resistance when challenged with a high-fat diet. Here, we have dissected the contributions of androgens and glucocorticoids to the metabolic phenotype using 2 models of enzyme inhibition (trangenesis and pharmacology).Female 5aR1−/− mice (KO) and w...

Hepatic A-ring reduction of glucocorticoids is enhanced in obesity, perhaps contributing to compensatory activation of the hypothalamic-pituitary-adrenal axis and adrenal androgen excess. One pathway activated is the formation of tetrahydro metabolites by two sequential steps catalysed by 5beta-reductase (5bR) followed by 3alpha-hydroxysteroid dehydrogenases (3HSD). However, regulation of these enzymes is understood poorly. 5bR and 3HSD are also involved in the conversion of c...

Glucocorticoids (cortisol in man, corticosterone in rodents) can inhibit angiogenesis, alter contractile function and reduce the inflammatory response to injury in the vascular wall. These effects are regulated by the 11beta-hydroxysteroid dehydrogenases (11HSDs) which inter-convert active glucocorticoids and their inactive 11-keto metabolites (cortisone; 11-dehydrocorticosterone) within target tissues. 11HSD2 is a unidirectional, exclusive dehydrogenase which inactivates gluc...

The contribution of conventional hormone replacement to the clinical features attributed to adult growth hormone deficiency (GHD) is poorly defined. We measured baseline bone mineral density (BMD/DXA) at the lumbar spine and femoral neck in patients with isolated GHD (IGHD, 16 patients, 14 female, 4 childhood onset, mean age 39, range 19- 63 years) and patients with multiple pituitary hormone deficiencies (MPD, 135 patients, 94 female, 14 childhood onset, mean age 44, range 19...

Maternal nutrient restriction (NR) during late-gestation can influence liver growth by altering maturation of the hypothalamus. Maternal NR during late-gestation increases fetal plasma GH levels whilst circulating IGF-I and IGF-II levels decrease. This study aimed to determine whether maternal NR during late-gestation altered the hepatic IGF system in resultant offspring.Fourteen primiparous twin pregnant Border Leicester cross Swaledale ewes were fed <i...

The contribution to adult growth hormone deficiency (GHD) of hormone replacement and other aspects of hypopituitarism are poorly defined. We compared baseline characteristics and response to GH treatment of patients with isolated GHD (IGHD, 16 patients) to patients with multiple pituitary hormone deficiencies (MPD, 135 patients). At baseline, MPD patients showed significantly greater waist-hip ratios (0.87 plus/minus 0.007 vs. 0.82 plus/minus 0.02, mean plus/minus SD; P < 0...

The route of oestrogen replacement has an important influence on growth hormone (GH) sensitivity, but it remains unclear whether the route of testosterone treatment in hypopituitarism influences the response to GH replacement. We have compared IGF-I levels, body composition and BMD in hypopituitary male patients with severe GH-deficiency receiving either oral testosterone undecanoate (T.U.)(80-160 milligrams per day) or intramuscular testosterone (I.M.) (250-500 milligrams per...

UK National Acromegaly Register collects data on real-life clinical practice in 34 centres. We analysed all GH and IGF1 data to assess adequacy of control on medical treatment (Rx) with somatostatin analogs (SMS) and dopamine agonists (DA).Methods: All GH records (basal, profile or GTT) in database were correlated with IGF1, Rx, surgery (TSS) and radiotherapy (RT), then processed to derive summary data for each patient and each course of Rx. GH considere...

The effect of growth hormone (GH) replacement on thyroid function in hypopituitary patients has only been studied in small groups of children and adults with conflicting results.We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of 243 patients with hypopituitarism due to various causes. 84 patients were considered euthyroid before GH treatment and 159 patients had central hypothyroidism an...

We have reported that serum DHEAS increases in growth hormone deficient (GHD) adults with intact ACTH reserve during GH replacement (GHR) in contrast with persisting low levels in ACTH-deficient GHD patients (Isidori et al. Clin Endo 2003:58:601). This was associated with a lower GH dose requirement in ACTH sufficient patients suggesting that DHEA may augment IGF-I generation. We have examined this hypothesis in a double blind placebo controlled trial of 30 hypopituitary femal...