It is known that both catecholamines (CA) and cortisol (F) levels elevate during labor. To determine the correlation between adrenal steroids and medullary function, maternal blood was collected during pregnancy, first stage of labor (MVI) and at delivery (MVII). Umbilical arterial and venous blood (UA, UV) was also obtained at delivery. Further, ACTH or dexamethasone (Dx) was given during the first stage of labor, and maternal blood was collected before and 30 minutes after the administration. Plasma levels of CA[noradrenaline (NA), adrenaline (Ad)] were extracted by trihydroxyindole method and were measured by HPLC. DHA-S and F levels were determined by specific RIA. Results are as follows: 1. No apparent change was observed in maternal NA and Ad levels throughout pregnancy. DHA-S levels were high in first trimester and decreased as pregnancy advanced, while F levels showed an increase trend as pregnancy progressed. 2. All hormone levels in maternal blood increased remarkably during labor. A significant negative correlation between F and Ad levels at delivery was noted. When F levels were elevated by ACTH administration, Ad levels decreased. Ad levels elevated when F levels were suppressed by Dx administration. 3. NA, Ad and DHA-S levels in cord blood were higher than those in MVII. Levels of F in maternal blood were higher than those in cord blood. A significant correlation of F in MVII and UA was observed. These results indicate that the suppressive effect of F may be involved in the mechanism of Ad secretion, though the secretion of Ad increased with F in the course of labor. The response of fetal adrenal to the stress of labor may be different from that of maternal adrenal since a significant correlation was not noticed between the levels of Ad and cortisol in cord blood as was found in maternal blood.
To study the serum levels of 19-hydroxyandrostenedione (19-OH-A), known as an obligatory intermediate of estrogen biosynthesis and considered to be one of the hypertensinogens, a method using GC-MS with application of synthesized [7,7-d2]androstenedione (A), [7,7-d2] 19-OH-A and [9,11-d2]estrone(E1) as internal standards was newly developed. Normal pregnant women and pregnant women complicated with hypertension near term were selected for the study. The levels of 19-OH-A and E1 increased significantly as gestation progressed [19-OH-A; 224.7 +/- 72.1 (1st trimester), 655.5 +/- 325.4 (2nd trimester). 1517.8 +/- 543.6 (3rd trimester)pg/ml], and a positive correlation was found between the levels of the two steroids. No apparent change was observed in A levels during the course of pregnancy. The mean levels of 19-OH-A in pregnancy complicated with hypertension at 2nd and 3rd trimester were 761.7 +/- 348.9 and 1473.0 +/- 491.4 pg/ml, which were compatible with those in normal pregnancy. The levels of 19-OH-A at delivery in maternal vein (MV) were 1735.1 +/- 683.9 pg/ml. Significantly higher levels of 19-OH-A were found in umbilical vein (UV) (1977.2 +/- 564.9 pg/ml) than those in umbilical artery (109.7 +/- 49.1 pg/ml). 19-OH-A concentration in term placental tissue was 16.3 ng/g.w.w. tissue. This is the first report to demonstrate the serum 19-OH-A levels measured by GC-MS and also to demonstrate the levels in the cord blood. The results indicate that 19-OH-A may be the product of pregnancy and may be derived from the feto-placental compartment.
19-hydroxyandrostenedione (19-OH A), known for many years as an obligatory intermediate of estrogen biosynthesis, has recently been found to be an amplifier of aldosterone action and in itself a hypertensinogenic steroid (J. Steroid Biochem., 16; 329, 1982). To search the presence of a non-aromatizing andorgen 19-hydroxylase in fetal organs, metabolism of labeled androstenedione(A) in fetal adrenal, liver, lung, brain and kidney was studied. 19-hydroxylase activity was calculated by the amounts of 19-OH A formed from A. The tissue homogenate was incubated with [4-14C]A and NADPH for different periods of time under air. The product, [4-14C] 19-OH A with added carrier standard [6,7-3H] 19-OH A was separated and purified by TLC, acetylation and TLC to constant 3H/14C ratio. The identity of the product was established by C.C.D. and by GC-MS analysis of purified product 19-AcOA in a larger scale adrenal incubation of non-labeled A. 19-hydroxylase activity was 0.9 pmol/min/mg protein for adrenal, but there was a negligible quantity of 19-OH A in lung, brain and kidney. Estrogen production was also assayed by 3H-water method using [1 beta-3H, 4-14C] A (3H/14C = 69.9). No detectable amount of estrogen was found in incubation of any homogenate except for liver. These results indicate that the non-aromatizing 19-hydroxylase activity in fetal adrenal gland is much higher than that in other organs. This is the first report to demonstrate the presence of 19-hydroxylase in human fetal adrenal tissue. It is suggested that 19-OH A secreted from fetal adrenal may also be associated with serum concentration of fetal circulation.
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