Effects of cortisol and estradiol on pituitary expression of proopiomelanocortin, prohormone convertase-1, prohormone convertase-2, and glucocorticoid receptor mRNA in fetal sheep.
We hypothesized that in the late-gestation sheep fetus there is an interaction between the prepartum rise in cortisol and the increase in placental estradiol production that allows expression of key components of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Therefore, the goal of this study was to investigate the effects of cortisol on the fetal HPA axis in the presence and absence of increased placental estradiol production. We obtained fetal plasma samples and pituitary tissue from animals that had received an infusion of either cortisol, cortisol and 4-hydroxyandrostenedione (40HA, an aromatase inhibitor), saline, or saline + 40HA controls. Cortisol significantly decreased plasma adrenocorticotropic hormone concentrations, and in the presence of 40HA reduced pituitary proopiomelanocortin (POMC) mRNA levels in the pars distalis. There was no effect of any treatment on the expression of the key POMC processing enzymes, prohormone convertase-1 or -2 in the fetal pituitary. Conversely, levels of glucocorticoid receptor (GR) mRNA in the pituitary were increased with cortisol treatment in the absence of increased estradiol. We suggest that in the late-gestation sheep fetus, cortisol and estradiol have opposite effects on pituitary POMC and GR mRNA expression, and interact to regulate these key components of the fetal HPA axis.
Holloway
A C
AC
Department of Physiology, University of Toronto, Ontario, Canada. alison.holloway@utoronto.ca
Whittle
W L
WL
Challis
J R
JR
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D045683:Furin; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis; D010902:Pituitary Gland / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis*; D012756:Sheep; D013381:Subtilisins / Q000096:biosynthesis*
D007527:Isoenzymes; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D004958:Estradiol; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D013381:Subtilisins; D045683:Furin; D006854:Hydrocortisone