title: Pituitary resistin gene expression is upregulated in vitro and in vivo by dexamethasone but is unaffected by rosiglitazone.
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)gamma, reportedly inhibit or stimulate resistin expression. Using quantitative real-time RT-PCR we determined that injection of DEX (10 and 50 microg) 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 microg). In AtT20 cells, exposure to corticosterone (10(-7) and 10(-6)M; 24 h) and DEX (10(-9)-10(-6)M) 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(-10)M; 24 h or 96 h) or the PPARgamma agonist GW 1929 (10(-9) and 10(-5)M; 24 h) had no effect on resistin mRNA. The PPARgamma antagonist GW 9662 (10(-6) and 10(-5)M) 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 PPARgamma-independent and therefore different from the situation in adipose tissue.
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, Dalhousie University, Halifax, Canada.
authors.forename: Russell
authors.initials: R
authors.lastname: Brown
authors.forename: Glen
authors.initials: G
authors.lastname: Wiesner
authors.forename: Ehud
authors.initials: E
authors.lastname: Ur
authors.forename: Michael
authors.initials: M
authors.lastname: Wilkinson
mesh_terms: D000315:Adrenalectomy / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005938:Glucocorticoids / Q000494:pharmacology*; D006729:Hormones, Ectopic / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology*; D012333:RNA, Messenger / Q000096:biosynthesis; D052243:Resistin; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005938:Glucocorticoids; D006729:Hormones, Ectopic; D012333:RNA, Messenger; D052243:Resistin; C499623:Retn protein, mouse; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D003907:Dexamethasone