Effects of labor on pituitary expression of proopiomelanocortin, prohormone convertase (PC)-1, PC-2, and glucocorticoid receptor mRNA in fetal sheep.
We hypothesized that the concurrent prepartum rise in adrenocorticotropic hormone (ACTH) and cortisol in the plasma of fetal sheep might be attributable to altered expression of pituitary endoproteases, prohormone convertase (PC)-1, and PC-2, or to changes in pituitary expression of glucocorticoid receptor (GR) that would influence negative feedback potential. We obtained pituitary tissue from fetal sheep during late pregnancy (d 100-d 145, term) and at precise times during the process of labor and used in situ hybridization to localize and quantify mRNA levels. Proopiomelanocortin (POMC) mRNA was regionally distributed (pars intermedia > inferior pars distalis > superior pars distalis) and increased within the pars distalis during late pregnancy and with labor. At term, levels of PC-1 and PC-2 mRNA were higher in the pars intermedia than pars distalis; PC-1 but not PC-2 in the pars distalis increased with gestational age, although it did not change further at labor. GR mRNA levels in the pars distalis increased between d 135 and term, then decreased during labor. We suggest that the concomitant rise in plasma ACTH and cortisol of fetal sheep during late gestation may be attributable, in part, to increased expression of PC-1 leading to increased POMC processing. Furthermore, the negative feedback effects of cortisol on pituitary POMC synthesis and/or ACTH release during active parturition may be lessened by downregulation of anterior pituitary GR.
Holloway
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AC
MRC Group in Fetal and Neonatal Health and Development, Toronto, Ontario, Canada. alison.holloway@utoronto.ca
Gyomorey
S
S
Challis
J R
JR
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D045683:Furin; D015870:Gene Expression; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood; D017403:In Situ Hybridization; D007743:Labor, Obstetric / Q000502:physiology*; D010902:Pituitary Gland / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D012333:RNA, Messenger / Q000032:analysis*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012756:Sheep; D013381:Subtilisins / Q000235:genetics*; D014018:Tissue Distribution
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D043484:Proprotein Convertases; D013381:Subtilisins; D045683:Furin; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases; D006854:Hydrocortisone