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Corticosteroid-binding globulin and estrogens in maternal and cord blood
Corticosteroid-binding globulifi and estrogens in maternal and cord blood EMERY
A.
ANN
E. FINN,
WILLIAM M.
WILSON,
JOE
Lexington,
M.D.
M.A.
RAYBURN, JAWAD,
M.D.
M.S.
Kentucky
Corticosteroid-binding globulih (CBG) is produced by the liver in small concentrations and binds steroids with high affinity. Its concentration in the blood is sensitive to endogenous or exogenous estrogens in a dose-response manner and serves as a biological assay for ~estrogens. CBG concentrations were measured in sera collected from maternal and umbilical vein blood during labor and delivery and at elective cesarean section and correlated with endogenous estracfrol and estriol concentrations. CBG and estradiol concentrations of niaternal blood were signikantty greater than that of the infant cord blood but estrlol levels in cord,blood significantly exceeded those of maternal serum. A highly significant increase ih cord blood estriol concentration was found following vaginal delivery compared to elective cesarean section, indicating an increase in adrenal activity due to the stress of labor. CBG levels c&related directly with maternal estradiol but not estriol concentrations. Cord blood CBG concentration varied little despite a wide range of estrogen concentrations. The physiologic significance of CBG concentrations in maternal and fetal blood is discussed. (AM.J.OBSTET.GYNECOL.
135:215,1979.)
IN 1958, Daughaday’ electrophoretically demonstrated a plasma protein called corticosteroid-binding globulin (CBG) which interacts reversibly,with steroids, particularly cornsol and progesterone. CBG, which has a molecular weight of approximately 53,000, is present in small concentrations and binds steroids with high affinity.* The hepatic production and plasma concentration of CBG vary directly with estrogen levels in a dose-response manner and serve as a biological assay for endogenous estrogen production. From University
the Department of Kentuc~
Received
of Obstetrics and Gynecology, College of Medicine.
for publication
Accepted November
October
25, 1978.
10, 1978.
Reprint requests: Dr. Emery A. Wilson, Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky 40506. 0002-9378/79/180215+04$00.40/O
@ 1979
The
C. V. Mosby
Co
Because of the difficulty in isolating CBG, the serum protein-binding capacity of cortisol provides a convenient and indirect measurement of CBG. During normal pregnancy, CBG increases to three times its initial value by 32 weeks’ gestation and remains stable until term.3 In this report CBG levels in maternal and cord blood are compared and correlated with serum concentrations of endogenous estrogens.
Material and methods Fifty-one patients with no prenatal complications were observed throughout gestation at the University of Kentucky Medical Center. Whole blood was obtained from 42 patients at the onset of labor. Following normal vaginal delivery, umbilical venous blood was also obtained. For comparison, nine maternal and umbilical venous blood samples were collected at the C
215
216
Wilson
et al.
September 15. 1979 Am. J, Obatet. Gvnc~ol.
Table I. CBG and estrogen maternal
and cord blood No. of
Blood
Maternal Cord
patients
42 42
*Significantly
concentrations (mean + SEM)
CBC hg4
Estradiol (nglml)
64.0 2 2.2 10.3 k 0.4*
different
20.1
iz 1.2
9.1 Ifr 0.7*
in
Estriol (ngM 15.3 2 1.1
134. -t 1.2.3*
from maternal values (p < 0.001).
Table II. CBG and estrogen maternal cesarean Blood
Maternal Cord
and cord blood section No. of patients 9 9
*Significantly
concentrations in (mean +- SEM) at elective
CBG (mg4 62.9
Estradiol (ngld)
5 5.7
9.1 -t- 0.9* different
26.8
+. 2.9
7.7 k 1.1*
Es&l (nglm0 16.2 -t 1.4 72.5 f 12.3*
from maternal values (p c 0.001).
time of repeat, elective cesarean section. All sera were stored at -20” C until assayed. All patients were delivered of normal, mature infants at term. Corticosteroid-binding capacity of serum was measured by the following technique: One-tenth milliliter of serum was stripped of its steroids by incubating with 0.6 ml of dextran-coated charcoal suspension for 30 minutes in a water bath at 45” C. After centrifugation at 2,500 x g for 10 minutes, 0.5 ml of supernate was obtained. Purified cortisol standard (Steraloids Inc., Wilton, New Hampshire, 80 ng, and tritiated cortisol (New England Nuclear, Boston, Massachusetts), 10,000 cpm, was added to the specimen which was then incubated at 37” C for 30 minutes and cooled at 4” C for 15 minutes. Bound and free cortisol were separated by centrifugation at 2,500 x g following a 30 minute incubation at 4” C with 0.6 ml dextran-coated charcoal suspension and the supernate containing cortisol-bound proteins was counted in a liquid-scintillation counter. Correction of the nonspecific binding was obtained by incubating 0.1 ml of patient serum with 0.6 ml of dextrancoated charcoal suspension at 60” C for 30 minutes prior to addition of cortisol. The amount of nonspecific binding was subtracted from the respective specimen. The intra-assay coefficient of variation for corticosteroid-binding capacity was less than 6%. Each molecule of CBG contains a single binding site for steroids.2 By determining the molar concentration of steroid bound, the concentration of CBG can be calculated and reported in milligrams per’liter of plasma. Estradiol and estriol concentrations were measured by direct radioimmunoassay methods previously described.4, 5 The estradiol and estriol antisera were specific, cross-reacting less than 1% with other estro-
gens, androgens, and progestins. The interassay coefficient of variation for estradiol and estriol was less than 12% and the intra-assay coefficient of variation was less than 9%.
Results The CBG and estradiol concentrations in maternal blood at the onset of labor were significantly greater than those of the infant cord blood but estriol levels in cord blood significantly exceeded those of maternal serum (Table I). The maternal CBG levels correlated with maternal endogenous estradiol (r = 0.550; p < 0.01) but not with estriol (r = 0.158) concentrations. The CBG of cord blood varied little despite a wide range of estrogen concentrations. In cord blood, no correlation between the CBG and estradiol (r = 0.223) or estriol (r = 0.208) concentrations was found. CBG and estrogen concentrations in maternal and cord blood at elective cesarean section are given in Table II. The reiationships between maternal and cord blood values were similar to those obtained in patients experiencing spontaneous labor and delivery. The differences in values between maternal and cord blood were highly significant. A slight but significant decrease in maternal estradiol concentrations (p < 0.05) and a highly significant increase in cord blood estriol concentrations (p < 0.001) were noted in the group of patients experiencing spontaneous labor and delivery when compared to patients undergoing elective cesarean section.
Comment CBG is an alpha-l globulin produced by the liver in small concentrations relative to other proteins but binds steroids with high affinity. CBG production responds to endogenous or exogenous estrogens in a dose-response manner and its increase is not known to be related to other hormones. Maximum increase in CBG concentration occurs after approximately 14 days of estrogen administration6 and its half life is 5.3 days7 Sandberg and associates7 have shown that the increase in concentration of CBG in response to estrogens is due to increased secretion by the liver and not to decreased turnover. Because of the Iong half life and low variability of CBG relative to the more widely fluctuating estrogen concentrations, CBG concentrations provide a stable representation of endogenous estrogen effect. Estrogens are the only steroids known to increase CBG concentration. The total pool of CBG in normal women is approximately 75 mg and in estrogen-treated women is 225 mg.’ Secondary to the increase in endogenous estrogens, CBG increases threefold during pregnancy.3 Its concentration may be low in complicated
Volume Number
CBG and estrogens in maternal and cord blood
135 2
217
pregnancies after the first trimester or in fetal death.* In nonpregnant patients, pharmacologic doses of es-
greater biological activity of estradiol in comparison with that of estriol. CBG concentrations in umbilical
trogens
vein
are
required
to increase
CBG
concentration6
Maternal unconjugated estradiol concentrations were consistently higher than estriol concentrations. This relationship was reversed in umbilical vein sera where the unconjugated estriol concentrations were some twelvefold greater than estradiol concentrations, reflecting greater placental secretion of estradiol into the maternal compartment whereas greater estriol secretion is directed to the fetal compartment. Although conjugated estrogens in maternal and fetal blood are much greater than unconjugated estrogens, the unconjugated estrogens are reported in this study because they would better reflect the effect of biological activity of estrogens on the production of serum proteins. Estradiol and estriol concentrations obtained in this study were similar to the results reported by others.‘-” Maternal serum was collected at the onset of labor to avoid changes in maternal estrogens during parturition. A slight but significant decrease in maternal estradiol was detected in these patients when compared to patients undergoing elective cesarean section. This decrease in estradiol is unexplained but it is consistent with a decrease in maternal estradiol after 40 weeks’ gestation reported by Turnbull and associates.‘* Labor may also alter fetal estrogens. Arai and colleaguesi reported a 25% increase in estriol concentrations and estrio1 precursors between fetal scalp blood during labor and umbilical cord blood obtained at the time of delivery. A similar increase in cord blood estriol concentrations following labor was detected in this study, indicating increased fetal adrenal function in reaction to the stress of labor. The corticosteroid-binding capacity of maternal sera at the onset of labor was significantly greater than that found in nonpregnant women. The CBG begins to increase during the first trimester, increases progressively until 28 to 32 weeks’ gestation, and then remains stable until term.3 Estrogen concentrations during pregnancy follow much the same pattern but continue to increase after 28 weeks. The CBG in maternal sera significantly correlated with endogenous estradiol concentrations but not estriol concentrations, indicating
sera
were
significantly
lower
than
those
of mater-
nal sera and even nonpregnant sera (unpublished data). No correlation of umbilical vein CBG with estradiol or estriol was detected. This lack of correlation in cord blood may have two possible explanations. Large concentrations of the impeded estrogen, estriol, may effectively compete with estradioland prevent a rise in corticosteroid-binding globulin. Katz and Kappas I4 studied the effects of estradiol and estriol on plasma levels of CBG and found that estradiol increased CBG whereas estriol, even in large dosages, showed no effect. However, the low variability of CBG found in cord blood despite a wide range of estradiol concentrations, in addition to the known evidence that the fetal and neonatal liver is enzymatically immature until approximately 6 months of life suggests that the fetal liver is incapable of increasing serum protein production in response to estrogens. The physiologic importance of increased CBG concentration during pregnancy and decreased CBG concentration in the fetus is presently unknown. Although the absolute amounts of total and free cortisol increase during pregnancy in maternal serum, so does the CBG concentration and the percentage of free metabolically active cortisol is unchanged throughout gestation. Although glucocorticoids have been reported to decrease the incidence of respiratory distress syndrome in newborn infants and, because estrogens increase the levels of CBG in the circulation, the concentration of CBG and the binding of cortisol may be of importance to fetal lung maturity. However, Sybulski and Maughan15 could find no correlation between umbilical cord plasma estradiol levels and cortisol levels. Further, we were unable to detect any correlation between estradiol and CBG concentrations in cord blood. The low CBG concentrations in cord blood may have physiologic significance in that the cortisol produced by the fetal adrenal during late gestation is largely unbound cortisol and is thus biologically active, which may facilitate maturation of the fetal lung or possibly the initiation of labor.
REFERENCES 1. Daughaday,
W. H.:
Binding
of corticosteroids
by plasma
proteins. IV. The electrophoretic demonstration of corticosteroid binding globulin, J. Clin. invest. 37:519, 1958. 2. Westphal, U.: Steroid-Protein Interactions, New York, 197 1, Springer-Verlag, p. 339. 3. Doe, R. P., Fernandez, R., and Seal, U. S.: Measurement of corticosteroid-binding globulin in man, J. Clin. Endocrinol.
Metab.
24: 1039,
1964.
4. England,
B. G., Niswender,
G. D., and Midgley,
A. R., Jr.:
Radioimmunoassay of estradiol- 170 without cbromatography, J. Ciin. Endocrinol. Metab. 38~42, 1974. 5. Abraham, G. E., Buster, J. E., Samojlik, R., et al: Comparison between four radioimmunoasays for plasma estrio], Anal. Letters 7: 119, 1974. 6. Muss, certain
B. U., Seal, U. S., and Doe, R. P.: Elevation of plasma proteins in man following estrogen admin-
218
Wilson
et al
September
Am. J. Obstet.
7:
8.
9.
10.
11.
istration: A dose-response relationship, J. Clin. Endocrinol. Metab. 25: 1163, 1965. Sandberg, A. A., Woodruff, M., Rosenthal, H., et al.: Transcortin: A Corticosteroid-binding protein of plasma. VII. Half-life in normal and estrogen-treated subjects, J. Chn. Invest. 4.3~461, 1964. DeMoor, P., Steeno, O., Brosens, I., et al.: Data on transcortin activity in human plasma as studied by gel filtration, J. Clin. Endocrinol. Metab. 26:71, 1966. Sarda. I. R., and Gorwill, R. H.: Hormonal studies in pregnancy. I. Total unconjugated estrogens in maternal peripheral vein, cord vein. and cord artery serum at delivery, AM. J. OBSTET. GYNECOL. 124~234, 1976. Cohen, M., and Cohen, H.: A radioimmunoassay for plasma unconjugated estrogens in normal pregnancy, AM. J. OBSTET. GYNECOL. 118:200, 1974. Cleary, R. E., and Young, P. C. M.: Serum unconjugated estriol in normal and abnormal pregnancy, AM. J. OBSTET. GYNECOL. 118:18, 1974.
15. 1979 Gvt~ecd.
12. Turnbull, A. C., Flint, A. P. F., Jeremy, J. Y.. Patten. P. T., Keirse, M. J. N. C., and Anderson, A. B. M.: Significant fall in progesterone and rise in oestradiol levels in human peripheral plasma before onset of labour. Lancer 1: 101, 1974. 13. Arai, K., Kuwabara, Y., Kihara, K., et al.: Steroid hormone levels in human fetal blood during delivery, AM. J. OBSTET. GYNECOL. 114~812, 1972. 14. Katz, F. H., and Kappas, A.: The effects of estradiol and estriol on plasma levels of cortisol and thyroid hormone-binding globulins and on aldosterone and cortisol secretion rates in man, J. Clin. Invest. 46~1768, 1967. 15. Sybulski, S., and Maughan, G. B.: Umbilical cord plasma e&radio1 levels in relation to complications of pregnancy and newborn and to cortisol levels. Biol. Neonate 27:302. 1975.
A.
ANN
E. FINN,
WILLIAM M.
WILSON,
JOE
Lexington,
M.D.
M.A.
RAYBURN, JAWAD,
M.D.
M.S.
Kentucky
Corticosteroid-binding globulih (CBG) is produced by the liver in small concentrations and binds steroids with high affinity. Its concentration in the blood is sensitive to endogenous or exogenous estrogens in a dose-response manner and serves as a biological assay for ~estrogens. CBG concentrations were measured in sera collected from maternal and umbilical vein blood during labor and delivery and at elective cesarean section and correlated with endogenous estracfrol and estriol concentrations. CBG and estradiol concentrations of niaternal blood were signikantty greater than that of the infant cord blood but estrlol levels in cord,blood significantly exceeded those of maternal serum. A highly significant increase ih cord blood estriol concentration was found following vaginal delivery compared to elective cesarean section, indicating an increase in adrenal activity due to the stress of labor. CBG levels c&related directly with maternal estradiol but not estriol concentrations. Cord blood CBG concentration varied little despite a wide range of estrogen concentrations. The physiologic significance of CBG concentrations in maternal and fetal blood is discussed. (AM.J.OBSTET.GYNECOL.
135:215,1979.)
IN 1958, Daughaday’ electrophoretically demonstrated a plasma protein called corticosteroid-binding globulin (CBG) which interacts reversibly,with steroids, particularly cornsol and progesterone. CBG, which has a molecular weight of approximately 53,000, is present in small concentrations and binds steroids with high affinity.* The hepatic production and plasma concentration of CBG vary directly with estrogen levels in a dose-response manner and serve as a biological assay for endogenous estrogen production. From University
the Department of Kentuc~
Received
of Obstetrics and Gynecology, College of Medicine.
for publication
Accepted November
October
25, 1978.
10, 1978.
Reprint requests: Dr. Emery A. Wilson, Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky 40506. 0002-9378/79/180215+04$00.40/O
@ 1979
The
C. V. Mosby
Co
Because of the difficulty in isolating CBG, the serum protein-binding capacity of cortisol provides a convenient and indirect measurement of CBG. During normal pregnancy, CBG increases to three times its initial value by 32 weeks’ gestation and remains stable until term.3 In this report CBG levels in maternal and cord blood are compared and correlated with serum concentrations of endogenous estrogens.
Material and methods Fifty-one patients with no prenatal complications were observed throughout gestation at the University of Kentucky Medical Center. Whole blood was obtained from 42 patients at the onset of labor. Following normal vaginal delivery, umbilical venous blood was also obtained. For comparison, nine maternal and umbilical venous blood samples were collected at the C
215
216
Wilson
et al.
September 15. 1979 Am. J, Obatet. Gvnc~ol.
Table I. CBG and estrogen maternal
and cord blood No. of
Blood
Maternal Cord
patients
42 42
*Significantly
concentrations (mean + SEM)
CBC hg4
Estradiol (nglml)
64.0 2 2.2 10.3 k 0.4*
different
20.1
iz 1.2
9.1 Ifr 0.7*
in
Estriol (ngM 15.3 2 1.1
134. -t 1.2.3*
from maternal values (p < 0.001).
Table II. CBG and estrogen maternal cesarean Blood
Maternal Cord
and cord blood section No. of patients 9 9
*Significantly
concentrations in (mean +- SEM) at elective
CBG (mg4 62.9
Estradiol (ngld)
5 5.7
9.1 -t- 0.9* different
26.8
+. 2.9
7.7 k 1.1*
Es&l (nglm0 16.2 -t 1.4 72.5 f 12.3*
from maternal values (p c 0.001).
time of repeat, elective cesarean section. All sera were stored at -20” C until assayed. All patients were delivered of normal, mature infants at term. Corticosteroid-binding capacity of serum was measured by the following technique: One-tenth milliliter of serum was stripped of its steroids by incubating with 0.6 ml of dextran-coated charcoal suspension for 30 minutes in a water bath at 45” C. After centrifugation at 2,500 x g for 10 minutes, 0.5 ml of supernate was obtained. Purified cortisol standard (Steraloids Inc., Wilton, New Hampshire, 80 ng, and tritiated cortisol (New England Nuclear, Boston, Massachusetts), 10,000 cpm, was added to the specimen which was then incubated at 37” C for 30 minutes and cooled at 4” C for 15 minutes. Bound and free cortisol were separated by centrifugation at 2,500 x g following a 30 minute incubation at 4” C with 0.6 ml dextran-coated charcoal suspension and the supernate containing cortisol-bound proteins was counted in a liquid-scintillation counter. Correction of the nonspecific binding was obtained by incubating 0.1 ml of patient serum with 0.6 ml of dextrancoated charcoal suspension at 60” C for 30 minutes prior to addition of cortisol. The amount of nonspecific binding was subtracted from the respective specimen. The intra-assay coefficient of variation for corticosteroid-binding capacity was less than 6%. Each molecule of CBG contains a single binding site for steroids.2 By determining the molar concentration of steroid bound, the concentration of CBG can be calculated and reported in milligrams per’liter of plasma. Estradiol and estriol concentrations were measured by direct radioimmunoassay methods previously described.4, 5 The estradiol and estriol antisera were specific, cross-reacting less than 1% with other estro-
gens, androgens, and progestins. The interassay coefficient of variation for estradiol and estriol was less than 12% and the intra-assay coefficient of variation was less than 9%.
Results The CBG and estradiol concentrations in maternal blood at the onset of labor were significantly greater than those of the infant cord blood but estriol levels in cord blood significantly exceeded those of maternal serum (Table I). The maternal CBG levels correlated with maternal endogenous estradiol (r = 0.550; p < 0.01) but not with estriol (r = 0.158) concentrations. The CBG of cord blood varied little despite a wide range of estrogen concentrations. In cord blood, no correlation between the CBG and estradiol (r = 0.223) or estriol (r = 0.208) concentrations was found. CBG and estrogen concentrations in maternal and cord blood at elective cesarean section are given in Table II. The reiationships between maternal and cord blood values were similar to those obtained in patients experiencing spontaneous labor and delivery. The differences in values between maternal and cord blood were highly significant. A slight but significant decrease in maternal estradiol concentrations (p < 0.05) and a highly significant increase in cord blood estriol concentrations (p < 0.001) were noted in the group of patients experiencing spontaneous labor and delivery when compared to patients undergoing elective cesarean section.
Comment CBG is an alpha-l globulin produced by the liver in small concentrations relative to other proteins but binds steroids with high affinity. CBG production responds to endogenous or exogenous estrogens in a dose-response manner and its increase is not known to be related to other hormones. Maximum increase in CBG concentration occurs after approximately 14 days of estrogen administration6 and its half life is 5.3 days7 Sandberg and associates7 have shown that the increase in concentration of CBG in response to estrogens is due to increased secretion by the liver and not to decreased turnover. Because of the Iong half life and low variability of CBG relative to the more widely fluctuating estrogen concentrations, CBG concentrations provide a stable representation of endogenous estrogen effect. Estrogens are the only steroids known to increase CBG concentration. The total pool of CBG in normal women is approximately 75 mg and in estrogen-treated women is 225 mg.’ Secondary to the increase in endogenous estrogens, CBG increases threefold during pregnancy.3 Its concentration may be low in complicated
Volume Number
CBG and estrogens in maternal and cord blood
135 2
217
pregnancies after the first trimester or in fetal death.* In nonpregnant patients, pharmacologic doses of es-
greater biological activity of estradiol in comparison with that of estriol. CBG concentrations in umbilical
trogens
vein
are
required
to increase
CBG
concentration6
Maternal unconjugated estradiol concentrations were consistently higher than estriol concentrations. This relationship was reversed in umbilical vein sera where the unconjugated estriol concentrations were some twelvefold greater than estradiol concentrations, reflecting greater placental secretion of estradiol into the maternal compartment whereas greater estriol secretion is directed to the fetal compartment. Although conjugated estrogens in maternal and fetal blood are much greater than unconjugated estrogens, the unconjugated estrogens are reported in this study because they would better reflect the effect of biological activity of estrogens on the production of serum proteins. Estradiol and estriol concentrations obtained in this study were similar to the results reported by others.‘-” Maternal serum was collected at the onset of labor to avoid changes in maternal estrogens during parturition. A slight but significant decrease in maternal estradiol was detected in these patients when compared to patients undergoing elective cesarean section. This decrease in estradiol is unexplained but it is consistent with a decrease in maternal estradiol after 40 weeks’ gestation reported by Turnbull and associates.‘* Labor may also alter fetal estrogens. Arai and colleaguesi reported a 25% increase in estriol concentrations and estrio1 precursors between fetal scalp blood during labor and umbilical cord blood obtained at the time of delivery. A similar increase in cord blood estriol concentrations following labor was detected in this study, indicating increased fetal adrenal function in reaction to the stress of labor. The corticosteroid-binding capacity of maternal sera at the onset of labor was significantly greater than that found in nonpregnant women. The CBG begins to increase during the first trimester, increases progressively until 28 to 32 weeks’ gestation, and then remains stable until term.3 Estrogen concentrations during pregnancy follow much the same pattern but continue to increase after 28 weeks. The CBG in maternal sera significantly correlated with endogenous estradiol concentrations but not estriol concentrations, indicating
sera
were
significantly
lower
than
those
of mater-
nal sera and even nonpregnant sera (unpublished data). No correlation of umbilical vein CBG with estradiol or estriol was detected. This lack of correlation in cord blood may have two possible explanations. Large concentrations of the impeded estrogen, estriol, may effectively compete with estradioland prevent a rise in corticosteroid-binding globulin. Katz and Kappas I4 studied the effects of estradiol and estriol on plasma levels of CBG and found that estradiol increased CBG whereas estriol, even in large dosages, showed no effect. However, the low variability of CBG found in cord blood despite a wide range of estradiol concentrations, in addition to the known evidence that the fetal and neonatal liver is enzymatically immature until approximately 6 months of life suggests that the fetal liver is incapable of increasing serum protein production in response to estrogens. The physiologic importance of increased CBG concentration during pregnancy and decreased CBG concentration in the fetus is presently unknown. Although the absolute amounts of total and free cortisol increase during pregnancy in maternal serum, so does the CBG concentration and the percentage of free metabolically active cortisol is unchanged throughout gestation. Although glucocorticoids have been reported to decrease the incidence of respiratory distress syndrome in newborn infants and, because estrogens increase the levels of CBG in the circulation, the concentration of CBG and the binding of cortisol may be of importance to fetal lung maturity. However, Sybulski and Maughan15 could find no correlation between umbilical cord plasma estradiol levels and cortisol levels. Further, we were unable to detect any correlation between estradiol and CBG concentrations in cord blood. The low CBG concentrations in cord blood may have physiologic significance in that the cortisol produced by the fetal adrenal during late gestation is largely unbound cortisol and is thus biologically active, which may facilitate maturation of the fetal lung or possibly the initiation of labor.
REFERENCES 1. Daughaday,
W. H.:
Binding
of corticosteroids
by plasma
proteins. IV. The electrophoretic demonstration of corticosteroid binding globulin, J. Clin. invest. 37:519, 1958. 2. Westphal, U.: Steroid-Protein Interactions, New York, 197 1, Springer-Verlag, p. 339. 3. Doe, R. P., Fernandez, R., and Seal, U. S.: Measurement of corticosteroid-binding globulin in man, J. Clin. Endocrinol.
Metab.
24: 1039,
1964.
4. England,
B. G., Niswender,
G. D., and Midgley,
A. R., Jr.:
Radioimmunoassay of estradiol- 170 without cbromatography, J. Ciin. Endocrinol. Metab. 38~42, 1974. 5. Abraham, G. E., Buster, J. E., Samojlik, R., et al: Comparison between four radioimmunoasays for plasma estrio], Anal. Letters 7: 119, 1974. 6. Muss, certain
B. U., Seal, U. S., and Doe, R. P.: Elevation of plasma proteins in man following estrogen admin-
218
Wilson
et al
September
Am. J. Obstet.
7:
8.
9.
10.
11.
istration: A dose-response relationship, J. Clin. Endocrinol. Metab. 25: 1163, 1965. Sandberg, A. A., Woodruff, M., Rosenthal, H., et al.: Transcortin: A Corticosteroid-binding protein of plasma. VII. Half-life in normal and estrogen-treated subjects, J. Chn. Invest. 4.3~461, 1964. DeMoor, P., Steeno, O., Brosens, I., et al.: Data on transcortin activity in human plasma as studied by gel filtration, J. Clin. Endocrinol. Metab. 26:71, 1966. Sarda. I. R., and Gorwill, R. H.: Hormonal studies in pregnancy. I. Total unconjugated estrogens in maternal peripheral vein, cord vein. and cord artery serum at delivery, AM. J. OBSTET. GYNECOL. 124~234, 1976. Cohen, M., and Cohen, H.: A radioimmunoassay for plasma unconjugated estrogens in normal pregnancy, AM. J. OBSTET. GYNECOL. 118:200, 1974. Cleary, R. E., and Young, P. C. M.: Serum unconjugated estriol in normal and abnormal pregnancy, AM. J. OBSTET. GYNECOL. 118:18, 1974.
15. 1979 Gvt~ecd.
12. Turnbull, A. C., Flint, A. P. F., Jeremy, J. Y.. Patten. P. T., Keirse, M. J. N. C., and Anderson, A. B. M.: Significant fall in progesterone and rise in oestradiol levels in human peripheral plasma before onset of labour. Lancer 1: 101, 1974. 13. Arai, K., Kuwabara, Y., Kihara, K., et al.: Steroid hormone levels in human fetal blood during delivery, AM. J. OBSTET. GYNECOL. 114~812, 1972. 14. Katz, F. H., and Kappas, A.: The effects of estradiol and estriol on plasma levels of cortisol and thyroid hormone-binding globulins and on aldosterone and cortisol secretion rates in man, J. Clin. Invest. 46~1768, 1967. 15. Sybulski, S., and Maughan, G. B.: Umbilical cord plasma e&radio1 levels in relation to complications of pregnancy and newborn and to cortisol levels. Biol. Neonate 27:302. 1975.