Induction of uterine prostaglandin H synthase 2 by estradiol following fetal adrenalectomy.
In sheep, fetal cortisol stimulates the conversion of progesterone to estradiol in late gestation initiating labor. It is unclear whether an intact fetal hypothalamic-pituitary-adrenal (HPA) axis is required to induce the estradiol-triggered subsequent endocrine changes including enhanced intrauterine prostaglandin (PG) synthesis associated with the onset of labor. We have shown that maternal estradiol administration stimulates PG H synthase (PGHS)-2 expressions in pregnant ovine intra-uterine tissues. The current study was undertaken to determine whether the fetal adrenal mediates estradiol's stimulation of the intrauterine PGHS-2 in pregnant sheep. Placenta, myometrium, and endometrium were collected from two groups of ewes at 123-127 d of gestational age (dGA) after fetal adrenalectomy and vehicle treatment (ADX; n = 5); or fetal ADX and maternal estradiol administration (5 mg twice a day for 2 d, ADX+E2, n = 5). PGHS-2 mRNA and protein were analyzed by Northern and Western Blot analyses in both groups and presented as the ratios to beta actin mRNA for Northern and G protein beta subunit for Western blot analysis. Fetal plasma cortisol was measured by radioimmunoassay. Data were analyzed by Student's t test. Fetal plasma cortisol levels were low in ADX and ADX+ E2 groups (<6 ng/mL). The cervix of all ADX+E2 treated ewes was dilated at necropsy. Three out of five ADX+ E2-treated ewes delivered within 48 h. The cervix was closed in all fetal ADX ewes at necropsy. PGHS-2 mRNA and protein increased (p < 0.05) in myometrium and endometrium, but not placenta in ADX+E2-treated ewes compared with ADX group. These data provide the first in vivo evidence for estradiol upregulation of intrauterine PGHS-2 in late gestation in the absence of an intact fetal HPA axis. Thus, the fetal adrenal is not required to mediate estradiol's stimulation of uterine PGHS-2 expression associated with the onset of labor.
Wu
W X
WX
Department of Obstetrics and Gynecology, Wake Forest University SOM, Dept. of Obstetrics and Gynecology, Winston-Salem, NC 27157, USA. wnewu@wfubmc.edu
Wolf
R
R
Chakrabarty
K
K
Collins
V
V
Unno
N
N
Nathanielsz
P W
PW
Rose
J C
JC
D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy / Q000662:veterinary; D000818:Animals; D015152:Blotting, Northern / Q000662:veterinary; D015153:Blotting, Western / Q000662:veterinary; D051546:Cyclooxygenase 2; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus; D006854:Hydrocortisone / Q000097:blood; D007743:Labor, Obstetric / Q000502:physiology*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012313:RNA / Q000737:chemistry / Q000235:genetics; D012756:Sheep / Q000502:physiology*; D014599:Uterus / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology
D004958:Estradiol; D012313:RNA; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D006854:Hydrocortisone