Endocrine Abstracts

In previous work we demonstrated that various adipokines, including leptin and resistin, were expressed in the hypothalamus and anterior pituitary gland. We hypothesized that a practical approach to investigate the putative central role of such factors would be to selectively silence gene expression by RNA interference (RNAi). We tested this hypothesis using model in vitro systems : C6 glioblastoma cells , which we reported express leptin, and 3T3-L1 adipocytes which are known...

The epidemic-like increase in obesity in young people is paralleled by a rise in related diseases such as PCOS, especially in pubertal girls. Kisspeptins, encoded by the KiSS1 gene, are firmly linked with the normal control of the reproductive system and loss-of-function mutations are associated with absence of puberty. Although KiSS1 is predominantly expressed in the hypothalamus (HYP), we detected KiSS1 mRNA in rat pituitary (PIT) and adipose tissue (FAT...

Obesity and adipokines are associated with a state of chronic low grade inflammation (Trayhurn & Wood 2004).In view of our findings that the adipokines resistin and fiaf (fasting-induced adipose factor) are also expressed in mouse brain and pituitary gland (Wiesner et al 2004), we tested the hypothesis that these factors would be induced in brain tissue following cerebral hypoxia/ischemia (H/I). Neonatal H/I (postnatal day 8; unilateral common c...

Adipokines such as resistin and FIAF (fasting-induced adipose factor) are predominantly, but not exclusively, expressed in adipose tissue and may modulate insulin sensitivity and lipid metabolism. We reported that resistin and fiaf mRNA, and resistin protein, are detectable in the mouse hypothalamus and pituitary gland (see eg. Wiesner et al. 2004). We are investigating the regulation of these genes in a novel hypothalamic neuronal cell line (n-1; Belsham ...

Resistin is a newly-described hormone whose expression in adipose tissue is regulated by fasting, insulin and obesity. We recently reported that resistin mRNA is also expressed in mouse hypothalamus and pituitary (FEBS Letts. 526, p26 (2002)). In the present study we hypothesized that adiposity would influence hypothalamic resistin immunoreactivity (ir). Two different, polyclonal antisera ( raised against aa 51-108, human ; aa 83-91, mouse ) revealed resistin ir in coronal sec...

We reported that leptin mRNA is developmentally regulated and hypothesized that local leptin expression is important for the maturation of the hypothalamic-pituitary system. Pituitary leptin mRNA levels were down-regulated in early postnatal male and female rats. We now show that pituitary leptin protein content and expression of the long (OBRb) and short (OBRa) leptin receptor isoforms in the pituitary and hypothalamus also undergo age-related changes. Tissue wa...

We have shown that linked polymorphisms in the aldosterone synthase gene (CYP11B2) are associated with hypertension and altered aldosterone production. However, the most consistent intermediate phenotype associated with this genetic variation is increased plasma 11-deoxycortisol (S) and urinary excretion of its metabolite, tetrahydrodeoxycortisol (THS); this is paradoxical as S is a substrate for the enzyme 11beta-hydroxylase, encoded by the neighbouring gene, CYP11B1. However...

Up to 15% of unselected patients with hypertension have evidence of inappropriate aldosterone production, identified by a raised ratio of plasma aldosterone to renin (ARR), suggesting that altered regulation of aldosterone synthesis is a key intermediate phenotype in essential hypertension. We previously described an association between the -344C/T 5'UTR polymorphism in the CYP11B2 (aldosterone synthase) gene and hypertension with raised ARR; the same genetic variation associa...

Background: The majority of patients with GH insensitivity have defects in the extracellular domain of the GHR. We have identified a 47yr old woman homozygous for a 22bp deletion in the cytoplasmic domain of the GHR. The patient had high GH levels, and low IGF-1 of 8 ug/L (normal 54-389 ug/L), IGFBP-3 16nmol/L (normal 61-254 nmol/L) and GHBP 6.8 percent (normal greater than 10 percent) levels. We report functional studies for this mutation (GHR1-449) which results in premature...