title: Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in adipose tissue in the sheep fetus during late gestation is dependent on plasma cortisol and triiodothyronine.
abstract: The endocrine regulation of uncoupling protein-2 (UCP2), an inner mitochondrial protein, in fetal adipose tissue remains unclear. The present study aimed to determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA abundance of UCP2, glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) and 2 (11betaHSD2) in fetal adipose tissue in the sheep during late gestation. Perirenal-abdominal adipose tissue was sampled from ovine fetuses to which either cortisol (2-3 mg kg(-1) day(-1)) or saline was infused for 5 days up to 127-130 days gestation, or near term fetuses (i.e. 142-145 days gestation) that were either adrenalectomised (AX) or remained intact. Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused animals and lower in AX fetuses compared with their corresponding control group, and increased with gestational age. UCP2 and GR mRNA abundance were significantly lower in AX fetuses compared with age-matched controls, and increased with gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose tissue was augmented by AX and suppressed by cortisol infusion, the latter also preventing the gestational increase in 11betaHSD1 mRNA and decrease in 11betaHSD2 mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3 concentrations were positively correlated with UCP2, GR and 11betaHSD2 mRNA abundance, but negatively correlated with 11betaHSD1 mRNA abundance. In conclusion, plasma cortisol and T3 are both required for the late gestation rise in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose tissue in the sheep during late gestation.
authors.affiliation: Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham NG7 2UH, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Gnanalingham
authors.forename: A
authors.initials: A
authors.lastname: Mostyn
authors.forename: A J
authors.initials: AJ
authors.lastname: Forhead
authors.forename: A L
authors.initials: AL
authors.lastname: Fowden
authors.forename: M E
authors.initials: ME
authors.lastname: Symonds
authors.forename: T
authors.initials: T
authors.lastname: Stephenson
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics; D000005:Abdomen; D000273:Adipose Tissue / Q000196:embryology / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood*; D007473:Ion Channels; D007668:Kidney; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics; D012756:Sheep; D014284:Triiodothyronine / Q000097:blood*; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D000071246:Uncoupling Protein 2; D014284:Triiodothyronine; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone