Effect of TGF-beta on dehydroepiandrosterone sulfotransferase in cultured human fetal adrenal cells.
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Adrenal Glands↗
Biomedical subjects
C R Parker
Publications and source records attributed to C R Parker.
Receptor binding of transforming growth factor-beta by human fetal adrenal cells.
We have shown previously that transforming growth factor beta 1 (TGF-beta 1) is antimitotic for human fetal adrenal (HFA) cells in vitro and that this effect can be partially blocked by adrenocorticotropic hormone (ACTH). In the present study, we sought to determine whether ACTH might interfere with TGF-beta 1 action by means of reducing TGF-beta 1 binding to adrenal cells. We incubated adrenal cells with 50 pM 125I-labeled TGF-beta 1 for 15 min to 3 h at 4 degree C and found that the binding of 125I-labeled TGF-beta 1 increased with time and could be inhibited in a dose-dependent manner by non-labeled TGF-beta 1 (0.05-10 nM), but not with other relevant cytokines: IL6, TNF alpha,IGF-I, IGF-II, TGF-alpha, and EGF. Pretreatment of HFA cells with ACTH (0.009-900 nM) for 4-24 h significantly increased specific 125I-labeled TGF-beta 1 binding compared to that in untreated cells; maximal increases in binding were achieved with 0.9 nM ACTH. This effect of ACTH could be mimicked by treatment of adrenal cells with dibutyryl cAMP (1 mM) or forskolin (10 microM). Scatchard analysis of data from ACTH-treated cells suggest the presence of two populations of TGF-beta 1 binding sites with different affinity and capacity of binding for the ligand.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Cortex↗
Maternal serum thromboxane B2 reduction versus pregnancy outcome in a low-dose aspirin trial.
OBJECTIVE: Our purpose was to determine whether in a low-dose aspirin trial a longitudinal decrease in maternal serum thromboxane B2 is associated with improvement in pregnancy outcomes. STUDY DESIGN: A total of 606 healthy nulliparous women with singleton gestations were randomized at 24 weeks to either 60 mg of aspirin or a placebo. Maternal serum thromboxane B2 was measured at randomization, at 29 to 31 weeks, at 34 to 36 weeks, and at delivery. After delivery, and without knowledge of patient outcome or group assignment, patients were categorized as having had either a longitudinal twofold or greater (> or = 50%) or less than twofold reduction (< 50%) in thromboxane B2 from baseline levels at randomization. RESULTS: Of 606 entrants, 92% had sufficient thromboxane B2 determinations to allow categorization. Whether patients were assigned to aspirin or placebo, birth weight was significantly greater in women who had a twofold or greater reduction in maternal serum thromboxane B2 levels. When the aspirin and placebo groups were combined, women with a twofold or greater reduction in thromboxane B2 levels had less preeclampsia, 1.9% (6/314) versus 5.7% (14/244) (p = 0.016), less preterm delivery (5.7% vs 10.7%, p = 0.032), fewer small-for-gestational-age newborns, 9 of 314 (2.95) versus 17 of 244 (7%) (p = 0.023), and a higher mean birth weight, 3314 gm versus 3121 gm (p = 0.0001). CONCLUSION: Women with a twofold or greater longitudinal reduction in maternal serum thromboxane B2 had less preeclampsia and prematurity, fewer small-for-gestational-age newborns, and higher birth weights than women with less than a twofold reduction.
Aspirin↗
Chronic hyperinsulinemia and the adrenal androgen response to acute corticotropin-(1-24) stimulation in hyperandrogenic women.
OBJECTIVE: Many women with androgen excess demonstrate elevated circulating insulin levels independent of obesity. In addition, in these women some investigators have demonstrated a negative correlation between the circulating levels of the adrenal androgens, dehydroepiandrosterone or dehydroepiandrosterone sulfate and insulin. The mechanism by which insulin decreases adrenal androgens is unclear. The objective of this study was to determine whether chronic hyperinsulinemia in hyperandrogenic women results in an alteration in the adrenocortical response to corticotropin, resulting in decreased androgen secretion. STUDY DESIGN: We studied seven hyperandrogenic women with severe chronic hyperinsulinemia and eight hyperandrogenic normoinsulinemic patients. Nine healthy women served as controls for the basal hormonal levels and the response to a 3-hour, 100 gm oral glucose tolerance test. In all subjects insulin and glucose were measured hourly during the oral glucose tolerance test and the baseline sample was assayed for total testosterone, dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, sex hormone-binding globulin, and free testosterone. In hyperandrogenic women cortisol, dehydroepiandrosterone, and androstenedione were also measured, before and 60 minutes, after acute intravenous administration of 0.25 mg corticotropin (1-24). RESULTS: There was no difference in the response of cortisol, dehydroepiandrosterone, or androstenedione to corticotropin-(1-24) stimulation between normoinsulinemic and hyperinsulinemic hyperandrogenic patients. As defined, the hyperinsulinemic patients had higher basal and peak insulin levels and areas under the insulin response curve compared with the normoinsulinemic patients or controls. Total testosterone and dehydroepiandrosterone did not differ among study groups. As expected, hyperandrogenic patients demonstrated lower sex hormone-binding globulin activity and higher free testosterone, androstenedione, and dehydroepiandrosterone sulfate basal levels compared with controls. CONCLUSIONS: The results of this study do not support the hypothesis that chronic hyperinsulinemia in hyperandrogenic patients significantly inhibits the andrenocortical secretion of dehydroepiandrosterone or androstenedione in response to corticotropin stimulation or the basal circulating adrenal androgen levels. Additional studies, including a greater number of patients, may be needed to fully establish these conclusions.
Adrenal Cortex↗
Low-dose aspirin: lack of association with an increase in abruptio placentae or perinatal mortality.
OBJECTIVE: To perform a meta-analysis determining the association of low-dose aspirin treatment with subsequent abruptio placentae or perinatal mortality. DATA SOURCES: Studies were identified and selected using the MEDLINE bibliographic data base of entries from January 1985 through April 1994. In addition, a manual search was performed using the references from all retrieved reports, review articles, and chapters from textbooks. METHODS OF STUDY SELECTION: Three criteria were used to select studies for inclusion: 1) Studies were designed as randomized or double-blind clinical trials; 2) aspirin was administered in doses of less than 200 mg/day; and 3) outcome data included the incidence of abruptio placentae and perinatal mortality. Three studies did not report the occurrence of abruptio placentae, but the authors of those papers answered written requests for such data. A total of 11 studies met our inclusion criteria. DATA EXTRACTION AND SYNTHESIS: We independently evaluated the study methods for each trial and abstracted quantitative outcome data. For each outcome, relative risk, risk differences, and 95% confidence intervals were calculated. The diagnosis of abruptio placentae was taken as self-reported in each trial. No trial of low-dose aspirin in pregnancy had predefined criteria for the diagnosis of abruptio placentae, and abruption was not a primary outcome in any of the 11 trials. We combined data from all studies and compared the data from the randomized trials to those from the double-blind studies. CONCLUSION: We found no increased risk for abruptio placentae or increased perinatal mortality in women taking low-dose aspirin.
Abruptio Placentae↗
Immunocytochemical analyses of dehydroepiandrosterone sulfotransferase in cultured human fetal adrenal cells.
Dehydroepiandrosterone sulfate is the major steroid secretory product of the human fetal adrenal gland. Several factors have been shown to modulate the secretion of this steroid by cultured fetal adrenal cells. In addition to the cytochrome P450 enzymes that are important in steroid biosynthesis, dehydroepiandrosterone sulfotransferase (DST) is likely to be a key regulated enzyme in the formation of sulfated steroids, which are characteristic of the human adrenal cortex, particularly that of the fetus and the adult zona reticularis. In the present investigation, we sought to evaluate the cellular localization of DST in cultures derived from the fetal zone, neocortex, and adrenal capsule and to determine the effects of ACTH and other agonists of the protein kinase-A pathway on the abundance of DST in such cells. Cells derived from the fetal zone, neocortex, and adrenal capsule were either precultured for 3-13 days in plastic flasks followed by culture on coverslips or were cultured directly on coverslips in control medium (McCoy's 5A medium that contained 5% fetal bovine serum) or control medium plus ACTH, forskolin, or dibutyryl cAMP for 1-4 days. Cells were fixed in buffered formalin and then immunostained for DST by use of a rabbit polyclonal antiserum prepared against human liver DST. DST immunoreactivity was abundant in freshly isolated cortical cells derived from fetal zone and neocortex. DST immunoreactivity was still observable in fetal zone and neocortex cells as well as in cells prepared from enzymatic digests of adrenal capsule after scraping off adherent neocortex cells following culture for 9-14 days in control medium. Adrenal fibroblasts were negative for DST. DST abundance in cortical cells was increased in cultures supplemented with ACTH, forskolin, or dibutyryl cAMP compared to that in cultures grown in control medium alone. The results of Western blot analyses of DST in these cells were consistent with the immunocytochemical data. These results suggest that DST is present in both fetal zone and neocortex cells of the human fetal adrenal at midgestation and that the production of DST is stimulated by ACTH and agonists of the protein kinase-A signal transduction pathway in the human fetal adrenal gland.
Adrenal Glands↗
Immunocytochemical analyses of dehydroepiandrosterone sulfotransferase in cultured human fetal adrenal cells.
Dehydroepiandrosterone sulfate is the major steroid secretory product of the human fetal adrenal gland. Several factors have been shown to modulate the secretion of this steroid by cultured fetal adrenal cells. In addition to the cytochrome P450 enzymes that are important in steroid biosynthesis, dehydroepiandrosterone sulfotransferase (DST) is likely to be a key regulated enzyme in the formation of sulfated steroids, which are characteristic of the human adrenal cortex, particularly that of the fetus and the adult zona reticularis. In the present investigation, we sought to evaluate the cellular localization of DST in cultures derived from the fetal zone, neocortex, and adrenal capsule and to determine the effects of ACTH and other agonists of the protein kinase-A pathway on the abundance of DST in such cells. Cells derived from the fetal zone, neocortex, and adrenal capsule were either precultured for 3-13 days in plastic flasks followed by culture on coverslips or were cultured directly on coverslips in control medium (McCoy's 5A medium that contained 5% fetal bovine serum) or control medium plus ACTH, forskolin, or dibutyryl cAMP for 1-4 days. Cells were fixed in buffered formalin and then immunostained for DST by use of a rabbit polyclonal antiserum prepared against human liver DST. DST immunoreactivity was abundant in freshly isolated cortical cells derived from fetal zone and neocortex. DST immunoreactivity was still observable in fetal zone and neocortex cells as well as in cells prepared from enzymatic digests of adrenal capsule after scraping off adherent neocortex cells following culture for 9-14 days in control medium. Adrenal fibroblasts were negative for DST. DST abundance in cortical cells was increased in cultures supplemented with ACTH, forskolin, or dibutyryl cAMP compared to that in cultures grown in control medium alone. The results of Western blot analyses of DST in these cells were consistent with the immunocytochemical data. These results suggest that DST is present in both fetal zone and neocortex cells of the human fetal adrenal at midgestation and that the production of DST is stimulated by ACTH and agonists of the protein kinase-A signal transduction pathway in the human fetal adrenal gland.
Adrenal Glands↗
Effects of transforming growth factor-beta on human fetal adrenal steroid production.
Transforming growth factor-beta (TGF-beta) was found to inhibit basal and ACTH-stimulated steroid production by cultured human fetal adrenal cells. The inhibitory effects of TGF-beta were both time and dose-dependent. Inhibition of basal dehydroepiandrosterone sulfate (DS) production usually was noted only after 3 or more days of treatment with > or = 0.1 ng TGF-beta/ml. The inhibitory effects of 1 ng/ml TGF-beta on ACTH-stimulated DS production were more striking than those on cortisol production by both fetal zone and neocortical cells. TGF-beta also was found to interfere with DS and cortisol production by fetal zone cells in response to forskolin and dibutyryl cAMP. TGF-beta interfered with ACTH stimulation of cytochrome P450(17) alpha mRNA in fetal zone and neocortex cells. These results are suggestive that TGF-beta differentially inhibits DS and cortisol production by human fetal adrenal cells and that the site of TGF-beta action on steroidogenesis may be distal to the generation of cAMP. Such results, along with those of others, are suggestive that TGF-beta may play an autocrine/paracrine role in the human adrenal.
Adenylyl Cyclases↗
Interactions between TGF-beta and adrenocorticotropin in growth regulation of human adrenal fetal zone cells.
The factors that regulate growth and function of the human adrenal gland during intrauterine development and thereafter are ill defined. Whereas others have reported that adrenocorticotropic hormone (ACTH) augments the inhibitory effect of transforming growth factor-beta (TGF-beta) on growth of fetal zone (FZ) cells of the human fetal adrenal, we recently found that ACTH interferes with TGF-beta's inhibition of growth of fetal adrenal neocortex cells. In this study we sought to assess independently the effects of TGF-beta in the absence and presence of ACTH on growth of FZ cells. TGF-beta, in a time- and dose-dependent manner, inhibited growth (i.e., [3H]thymidine incorporation) of FZ cells. ACTH (Cortrosyn), at 90 pM to 90 nM, was found to interfere with the TGF-beta inhibition of FZ growth. ACTH 1-24 and human ACTH 1-39, both from Sigma Chemical, also were found to blunt the response of FZ cells to TGF-beta. Growth inhibition due to TGF-beta action and the reversal by ACTH of TGF-beta effects on FZ cell growth were confirmed by the results of immunohistochemical analyses of 5'-bromo-2'-deoxyuridine incorporation into nuclei of FZ cells and by indirect evaluations of cell numbers. Both forskolin (10 microM) and dibutyryl adenosine 3',5'-cyclic monophosphate (1 mM), but not phorbol 12-myristate 13-acetate (1 or 100 mM), were able to mimic ACTH actions in blunting the inhibitory effects of TGF-beta on DNA synthesis. We conclude that ACTH, possibly via activation of adenylate cyclase, interferes with, rather than augments, the growth-inhibitory effect of TGF-beta on FZ cell growth.
Adrenal Glands↗
Abnormal adrenal steroidogenesis in growth-retarded newborn infants.
The results of prior studies suggest that abnormalities of development and function of the fetal adrenal occur in pregnancies complicated by intrauterine fetal growth retardation (IUGR). In the present investigation, we sought to extend such studies by matching IUGR infants with normally grown infants of women in whom pregnancy complications, delivery method, and gestational age were comparable. In 47 vaginally delivered, IUGR infants (38 +/- 2 wk, mean +/- SD; 2244 +/- 589 g body weight), the levels of dehydroepiandrosterone sulfate (DS) in umbilical cord serum (4.48 +/- 2.94 mumol/L) were lower (p = 0.035) than those (5.94 +/- 3.63 mumol/L) of 47 normal weight infants (38 +/- 2 wk; 3107 +/- 527 g). Yet, umbilical cord serum levels of cortisol in IUGR infants (455 +/- 189 nmol/L) were slightly higher than those of the control infants (408 +/- 247 nmol/L). The DS/cortisol molar ratio in IUGR infants (10.5 +/- 6.8) was 41% lower (p = 0.0013) than that of the control infants (17.7 +/- 13). Also, the estimated DS plasma pool in IUGR infants (521 +/- 349 nmol) was strikingly lower (p = 0.0018) than that of the control infants (800 +/- 480 nmol); the estimated plasma pools of cortisol were equivalent (growth-retarded: 53 +/- 27 nmol; control: 55 +/- 34 nmol). Although we anticipated that total cholesterol and apo B levels in IUGR infants would be increased due to reduced adrenal utilization of LDL for DS production, such was not the case. We conclude that a selective deficiency of DS production occurs in the IUGR fetus.
Adrenal Glands↗
Immunohistochemical localization of dehydroepiandrosterone sulfotransferase in human fetal tissues.
Sulfurylation of many steroid hormones has been found to occur in several tissues of the fetal and adult human. Because the production of prodigious quantities of dehydroepiandrosterone sulfate in the developing fetus is believed to be of signal importance in the hyperestrogenic state that is characteristic of human pregnancy, we sought to define the tissue sites that contain dehydroepiandrosterone sulfotransferase (DST). To this end, antibodies directed against purified human liver DST were employed for the immunohistochemical localization of DST in several fetal tissues. Abundant DST was found in the fetal and neocortical zones of the adrenal cortex, liver, testis, and intestine. Collecting ducts of the kidney were weakly positive for DST. DST immunostaining was not observed in spleen, thymus, lung, brain, heart, stomach, pancreas, or skeletal muscle. The tissue localization of DST immunoreactivity is consistent with the reported localization of enzymatic activity determined during in vitro studies on sulfurylation of C19 and C21 steroids. On the other hand, DST localization does not correspond as well to the sites of estrogen sulfurylation found by others. These data suggest that a single enzyme may be responsible for sulfurylation of C19 and C21 steroids in the developing human.
Fetus↗
Steroid secretory characteristics of a virilizing adrenal adenoma in a woman.
A tumour of the left adrenal gland was identified in a woman who presented with virilization and secondary amenorrhea. Preoperatively, the plasma levels of dehydroepiandrosterone sulphate, dehydroepiandrosterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and 5-androstene-3 beta,17 beta-diol were elevated two- to fourfold whereas those of urinary 17-ketosteroids were elevated more than tenfold. The production rate of dehydroepiandrosterone sulphate was more than 16 times that in normal women whereas those of dehydroepiandrosterone, testosterone and androstenedione were approximately twofold greater; plasma testosterone was derived almost entirely from the peripheral conversion of androstenedione. Blood was obtained by catheterization of the ovarian veins, left adrenal gland vein and inferior vena cava (at two different sites) and plasma steroid levels were determined: testosterone and cortisol levels were elevated in all blood samples whereas those of androstenedione, dehydroepiandrosterone sulphate and 11-desoxycortisol were approximately six- to eightfold, 1.5-fold and nine- to 22-fold higher in the effluent on the left adrenal gland/tumour compared with the levels in the other compartments. Blood was collected hourly for 24 h to determine steroid levels under basal conditions and, also, after ACTH treatment. Plasma cortisol levels increased markedly upon ACTH administration and fell to very low levels 11 h later, but those of androstenedione, testosterone, dehydroepiandrosterone, 5-androstene-3 beta,17 beta-diol and dehydroepiandrosterone sulphate were not affected by ACTH treatment. A histological diagnosis of cortical adenoma of the extirpated tumour was made. Tissue explants and adenoma cells were maintained in culture to characterize the steroid-metabolizing properties of the tumour. The secretion of dehydroepiandrosterone sulphate by tissue explants was highly initially, but declined to almost undetectable levels after 5 days in culture. In the presence of ACTH, dehydroepiandrosterone sulphate secretion remained elevated throughout the entire study up to 5 days. Basal secretion of dehydroepiandrosterone sulphate, androstenedione, 11-desoxycortisol, cortisol, testosterone and 11 beta-hydroxyandrostenedione by adenoma cells was either very low or undetectable. In the presence of ACTH, dibutyryl cyclic AMP or cholera toxin the secretion of dehydroepiandrosterone sulphate, androstenedione and 11-desoxycortisol increased markedly with time in culture up to 3 days, whereas the other steroids were undetected in the medium. A homogenate of adenoma tissue metabolized testosterone to androstenedione, but the conversion of androstenedione to testosterone was minimal. The findings of this study served to establish that virilization in this woman was due at least in part, to excess testosterone--and testosterone-derived 5 alpha-dihydrotestosterone--produced at extra-adrenal tissue sites almost exclusively through metabolism of tumour-secreted androstenedione.(ABSTRACT TRUNCATED AT 400 WORDS)
17-Ketosteroids↗
The effect of low-dose aspirin on fetal urine output and amniotic fluid volume.
OBJECTIVE: Patients given prostaglandin synthetase inhibitors in doses sufficient to inhibit labor are at risk for developing oligohydramnios (possibly related to a reduction in fetal urine output). We sought to ascertain whether the fetuses of women who received 60 mg of aspirin daily had a lower urine output than those whose mothers were given a placebo. STUDY DESIGN: Nulliparous women with singleton gestations in a double-blind preeclampsia prevention trial were randomly selected at 24 weeks' gestation to receive either 60 mg of aspirin daily or a placebo. Urine output was assessed in 59 fetuses (aspirin 32, placebo 27) by serial ultrasonographic measurement of their bladder volume (volume = 4/3 pi r3). Biochemical evidence of aspirin compliance was defined as an 80% reduction in maternal serum thromboxane B2 levels when comparing values obtained at randomization with those at 34 to 36 weeks' gestation. RESULTS: Visual assessment of amniotic fluid volume was similar in both groups. Four-quadrant amniotic fluid indexes also were similar (13.5 cm in aspirin group vs 12.2 cm in placebo group, p = 0.15). Mean fetal urine outputs were similar in the aspirin (57.7 ml/hr) and placebo (55.1 ml/hr) groups (p = 0.71). Moreover, the 23 women with a fourfold thromboxane B2 reduction had a higher mean fetal urine output (63.5 vs 51.8 ml/hr, p = 0.08) than did the remaining 35 patients. This study has a 96% chance (1-beta) of detecting a 50% (30 ml) reduction in fetal urine output. CONCLUSIONS: Daily maternal ingestion of 60 mg of aspirin did not decrease fetal urine output or amniotic fluid volume.
Adult↗
The effect of low-dose aspirin on umbilical artery Doppler measurements.
OBJECTIVE: Our purpose was to determine if the maternal administration of low-dose (60 mg) aspirin from 24 weeks' gestation until delivery is associated with significant changes in longitudinal umbilical artery Doppler index values. STUDY DESIGN: Healthy, young nulliparous women with singleton gestations who were enrolled in a double-blind trial of low-dose aspirin for preeclampsia prevention underwent prerandomization and monthly postrandomization continuous-wave umbilical artery Doppler evaluations. The systolic-to-diastolic ratio and the resistance index were determined at each examination. Compliance with the medical regimen was assessed by pill counts and measurement of maternal serum thromboxane B2 levels. RESULTS: The prerandomization Doppler index values were similar between the two randomization groups in the 538 (aspirin 266, placebo 272) patients studied. We found no significant differences with univariate comparisons and multiple linear regression modeling in the postrandomization Doppler index values (p = 0.21 to 0.96). No differences were found when patients were assessed by randomization assignment group (intent to treat) or by biochemical evidence for compliance and absence of crossover with maternal serum thromboxane B2 levels. CONCLUSION: The use of low-dose aspirin from 24 weeks' gestation until delivery does not significantly affect umbilical artery Doppler index values.
Aspirin↗
Midpregnancy serum thromboxane B2 determinations do not predict subsequent adverse pregnancy outcomes.
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Female↗
Low-dose aspirin therapy to prevent preeclampsia.
OBJECTIVE: Our aim was to test the hypothesis that acetylsalicylate (aspirin) treatment reduces the incidence or severity of pregnancy-associated hypertension. STUDY DESIGN: Patients were nulliparous, healthy, and with a singleton gestation at between 20 and 22 weeks' gestation. A sample size of 600 patients was calculated on the basis of p < or = 0.05 and 90% power of observation. A 2-week placebo-controlled "run-in" was used to select compliant patients. Randomization occurred at 24 weeks, with 60 mg of aspirin or placebo treatment from randomization to delivery. RESULTS: Follow-up was maintained on 99% of the patients. The randomized patients had a 94% pill compliance index. At randomization, serum thromboxane medians were similar in both groups. Thromboxane B2 levels in the aspirin group decreased significantly from baseline at 29 to 31 weeks, 34 to 36 weeks, and at delivery as compared with an overall increase in the placebo group. Preeclampsia developed in five of 302 women (1.7%) who received aspirin versus 17 of 302 (5.6%) who received the placebo (p = 0.009). Preeclampsia was severe in one aspirin and in six placebo recipients (p = 0.06). CONCLUSION: Daily ingestion of 60 mg of aspirin beginning at 24 weeks' gestation significantly reduced the occurrence of preeclampsia.
Adult↗
Effects of intrapartum stress on fetal adrenal function.
OBJECTIVE: Our purpose was to characterize the fetal adrenal response to acute intrapartum stress in otherwise uncomplicated pregnancies. STUDY DESIGN: Term infants (n = 61) diagnosed as having fetal distress during labor, as indicated by heart rate abnormalities, and delivered of women having normal pregnancies were pair-matched with 61 infants showing no signs of fetal distress or acidemia (controls) on the basis of gestational age and delivery method. Umbilical cord serum dehydroepiandrosterone sulfate and cortisol were measured, and the data were analyzed by two-tailed t test, Fisher's exact test, analysis of variance, and Tukey's multiple range test. RESULTS: Distressed infants had lower serum levels of dehydroepiandrosterone sulfate (3992 +/- 246 nmol/L, mean +/- SE) than control infants (4853 +/- 283 nmol/L); distressed infants also had higher levels of cortisol (412 +/- 17 nmol/L) than did control infants (299 +/- 16 nmol/L). The dehydroepiandrosterone sulfate/cortisol ratios in control infants (17.7 +/- 1.2) were almost twice those of distressed infants (10.8 +/- 0.9). These same relationships also were noted when the infant pairs were segregated according to whether delivered vaginally (21 pairs) or by cesarean section (40 pairs). The abnormalities in steroid levels in the distressed infants were independent of the presence or absence of acidemia. CONCLUSION: Intrapartum stress acutely alters fetal adrenal steroidogenesis, leading to increased production of cortisol and decreased secretion of dehydroepiandrosterone sulfate.
Adrenal Glands↗
Systemic and uterine responses to chronic infusion of estradiol-17 beta.
Human and ovine pregnancies are associated with increases in plasma levels of estrogens and angiotensin II (ANG II), cardiac output (CO), blood volume (BV), and uterine blood flow (UBF), as well as attenuated ANG II pressor responses. We hypothesized that, in nonpregnant animals, prolonged estradiol-17 beta (E2 beta) treatment would reproduce these endocrine and hemodynamic alterations. Nonpregnant ovariectomized ewes (n = 5) received 5 microgram E2 beta/kg iv followed by 220 micrograms/day for 14 days. Plasma E2 beta increased from 36 +/- 6 to 269 +/- 79 (SE) pg/ml (P < 0.05) during E2 beta treatment, returning to control values 4 days posttreatment. By 3 days of E2 beta, mean arterial pressure (MAP) and systemic vascular resistance (SVR) fell 9 +/- 1 and 29 +/- 1%, whereas heart rate (HR) and CO increased 20 +/- 5 and 26 +/- 1% (P < 0.05). Stroke volume (SV), BV, and plasma volume were unchanged until 7 days of E2 beta, with values rising 17 +/- 5, 13 +/- 3, and 14 +/- 4, respectively (P < 0.05). Although MAP remained similarly depressed (-11 +/- 1%) during week 2 of E2 beta, SVR decreased further (-37 +/- 3%) and was associated with additional increases (P < 0.05) in CO to 44 +/- 5%, reflecting rises in SV (21 +/- 2%) but not HR. Increases in BV correlated with rises in CO (r = 0.55) and SV (r = 0.64) but not HR (r = -0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗