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Vol. 81, No. 1, 2005
Issue release date: 2005
Neuroendocrinology 2005;81:41–48
(DOI:10.1159/000084873)

Pituitary Resistin Gene Expression Is Upregulated in vitro and in vivo by Dexamethasone but Is Unaffected by Rosiglitazone

Brown R. · Wiesner G. · Ur E. · Wilkinson M.
Departments of aObstetrics and Gynaecology, bPhysiology and Biophysics, cDivision of Endocrinology and Metabolism, Faculty of Medicine, Dalhousie University, Halifax, Canada, and dHuman Neurotransmitter Laboratory, Baker Institute, Melbourne, Australia

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Abstract

A physiological role for the adipose-derived hormone, resistin, remains unsolved and its putative involvement in insulin resistance is largely controversial. Like leptin and other adipokines, we detected resistin in the rodent hypothalamic-pituitary system. In addition, the pituitary corticotrope cell line, AtT20, is also a source of resistin. These data suggested that resistin could be involved in diverse physiological processes in non-adipose tissue. Initial studies indicated that pituitary resistin gene expression was regulated in a nutritional (fed > fasted), age- (young > old) and gender-specific manner (male > female). In the present work we hypothesized that pituitary resistin expression should be regulated through signalling pathways similar to those reported for adipose tissue. For example, dexamethasone (DEX) potently stimulates production of resistin in murine adipose tissue, whereas thiazolidinediones such as rosiglitazone (ROSI), acting via peroxisome proliferator-activated receptor (PPAR)γ, reportedly inhibit or stimulate resistin expression. Using quantitative real-time RT-PCR we determined that injection of DEX (10 and 50 µg) yielded 7- and 9-fold increases in pituitary resistin gene expression in prepubertal, but not adult mice. In addition, adrenalectomy attenuated pituitary resistin gene expression, which was restored by DEX (10 µg). In AtT20 cells, exposure to corticosterone (10–7 and 10–6M; 24 h) and DEX (10–9–10–6M) stimulated resistin mRNA more than 65% (p < 0.05) and 115% (p < 0.0001), respectively. In contrast, ROSI, injected (5 and 20 mg/kg s.c. for 14 days) or given orally (3 mg/kg/day to 10 mg/kg/day for up to 7 weeks), failed to alter pituitary resistin gene expression in healthy male CD1 mice. Treatment of AtT20 cells with ROSI (10–5–10–10M; 24 h or 96 h) or the PPARγ agonist GW 1929 (10–9 and 10–5M; 24 h) had no effect on resistin mRNA. The PPARγ antagonist GW 9662 (10–6 and 10–5M) was also ineffective. In conclusion, pituitary resistin mRNA levels are robustly stimulated by corticosteroids, particularly at the time of puberty. This is consistent with our previous suggestion that resistin may be involved in maturation of the hypothalamic-pituitary axis. In contrast, pituitary resistin gene expression appears to be PPARγ-independent and therefore different from the situation in adipose tissue.



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