羊胎仔成熟過程における視床下部-下垂体-副腎系の役割 : 母体副腎系との相関の視点から (<シンポジウム>1. 胎児の発達と母児相関)

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Exp. 1: To characterize ontogenic changes in baseline and 24-h rhythms of fetal arterial blood pressure (BP) and heart rate (FHR) in the late gestation fetal sheep, seven pregnant ewes were chronically instrumented, and hourly BP and FHR were recorded continuously from 120 days gestation (dGA) to 138 dGA. Averaged BP and FHR for 120-125 dGA (Period 1), 126-132 dGA (Period 2), and 133-138 dGA (Period 3) were compared. Regression analysis was applied, and slopes of regression lines were compared between Period 1 and Period 3. Cosinor analysis was applied to evaluate 24-h rhythms of BP and FHR. BP increased and FHR decreased steadily with gestational age. Slopes of the BP increases during Period 3 were significantly greater than those during Period 1, while no difference was found in the slopes of FHR decreases. Significant 24-h rhythms in BP and FHR were. No significant changes in the 24-h rhythms in BP and FHR were found. Exp. 2: To examine effects of fetal adrenalectomy (ADX), with or without subsequent cortisol (F) supplementation, on the gestational age related changes in BP and FHR, thirteen pregnant ewes were instrumented at 110 dGA. Fetal adrenals were removed in eight animals (ADX) ; sham fetal adrenalectomy was performed on five animals (CONT). BP and FHR were measured continuously from day six. F (4 μg/min^<-1>) was infused i.v. to four ADX fetuses from day seven for seven days (ADX + F). F infusion increased fetal plasma F from <4.9 ng・ml^<-1> to around 20 ng・ml^<-1> in ADX + F fetuses. A significant increase in BP and a decrease in FHR with gestation were observed in CONT fetuses. In ADX fetuses, BP remained unchanged, while FHR decreased. Significant increases in both BP and FHR sustained for up to six days were observed in ADX + F fetuses. Exp. 3: CRH and AVP produced in the parvocellular neurons of the paraventricular nucleus (PVN) have been implicated in the regulation of anterior pituitary ACTH secretion. In sheep, the activation of the fetal hypothalamo-pituitary-adrenal axis (HPAA) occurs around 120-125 dGA. We investigated the effects of adrenalectomy and F administration on PVN CRH and AVP mRNA. Fetal hypothalami were collected at 124 dGA in the animals studied in Exp. 2, and studied by in-situ hybridization and quantitative autoradiography for CRH and AVP mRNA. PVN CRH mRNA expression was augmented in ADX and suppressed in ADX + F. AVP mRNA in the parvocellular PVN showed a significant increase in ADX and suppression in ADX + F fetuses while AVP mRNA in the magnocellular PVN remained unchanged. Exp. 4: Effects of inhibition of PG synthesis on the fetal HPAA during parturition have not been characterized. Two isoforms of cyclooxygenase exist, COX-1, a constitutive form, and COX-2, an inducible form. We examined COX-2 regulation of fetal HPAA activation during spontaneous term labor using nimesulide (NIM), a putative selective inhibitor of COX-2. Four pregnant ewes were instrumented. After onset of labor NIM was infused to the ewe i.v.. Following NIM infusion, fetal plasma PGE_2, ACTH and F showed significant decreases. Conclusions: In fetal sheep at late gestation: 1) The ontogenic increase in BP is significantly accelerated at around 130-135 dGA, while the FHR decrease rate remains unaltered; 2) Twenty four-h rhythms in BP and FHR exist from 120 dGA to 138 dGA, which remains unchanged throughout the period; 3) The physiological increase in BP is dependent on the fetal adrenal; 4) F supplementation in ADX fetuses can maintain an incvease in BP and FHR; 5) ADX augments CRH and AVP mRNA expression in the parvocellular PVN; 6) Increased parvocellular CRH and AVP mRNA expressions after ADX are suppressible by F; 7) CRH and AVP mRNA abundance in the parvocellular PVN are under glucocorticoid feed-back control; 8) COX-2 plays physiologic roles in activation of the ovine fetal HPAA during labor.
社団法人日本産科婦人科学会の論文
1997-08-01

羊胎仔成熟過程における視床下部-下垂体-副腎系の役割 : 母体副腎系との相関の視点から (<シンポジウム>1. 胎児の発達と母児相関)

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