0021-972x/92/7503-0906$03.00/0 Journal of Clinical Endocrinology and Metabolism Copyright 0 1992 by The Endocrine Society
Vol. 15, No. 3 Printed in U.S.A.
Highest Concentrations of Prorenin and Human Chorionic Gonadotropin in Gestational Sacs During Early Human Pregnancy* JOSEPH ITSKOVITZ JEAN E. SEALEY
(ELDOR),
SPERANZA
RUBATTU?,
JACOB
LEVRON,
AND
Department of Obstetrics and Gynecology, Rambam Medical Center (J.I., J.L.) and Technion-Israel Institute of Technology, Faculty of Medicine (J.I.), Haifa 31096, Israel; and Cardiovascular Center, The New York Hospital-Cornell University Medical College (S.R., J.E.S.), New York, New York 10021 ABSTRACT Prorenin is not only the biosynthetic precursor of renin; under certain circumstances in vitro prorenin exhibits reversible intrinsic renin activity and can form angiotensin from renin substrate with or without cleavage of the prosequence. Prorenin is the predominant form of renin synthesized by reproductive organs (ovary, chorion laeve of the placenta, uterine decidua). Its plasma concentrations increases lofold throughout pregnancy to lo-100 times that of renin; amniotic fluid prorenin concentration is even higher. No data are available of gestational fluid prorenin concentrations during early pregnancy. For the first 10 weeks there are two gestational cavities; the chorionic cavity then disappears and the smaller amniotic cavity becomes predominant. In this study we measured prorenin, renin, renin substrate and hCG in fluid aspirated from gestational sacs during the first trimester of gestation (predominantly chorionic) and during the second and third trimesters (amniotic). Seventeen patients had amniocentesis during the second or third trimester. Nine patients underwent selective abortion of multiple pregnancy at 7-12 weeks gestation. One patient under-
went surgery at 5% weeks (26 days after conception) for a tubal pregnancy. Second and third trimester amniotic fluid prorenin maximum velocity (V,.,) (16 and 3 sacs, respectively) averaged 6,100 + 1,700 (SD) and 1,930 + 760 ng/mL. h, respectively (i.e. 1,700 and 540 ng/L.s). In gestational fluid collected before 8 weeks, prorenin V,., was lo-fold higher, averaging 62,500 + 40,000 ng/mL. h (17,000 ng/L.s). The concentration was 140,000 ng/mL. h (39,000 ng/L.s) in the 5% week tubal pregnancy. In sharp contrast, at lo-12 weeks gestation (n = 3) prorenin V,., was only 260 + 114 ng/mL. h (72 ng/L.s); human CG was also highest before 8 weeks (276,500 + 110,900 W/L) and lowest at lo-12 weeks (1210 f 540 IU/L) with intermediate levels occurring later in pregnancy. This study shows that the highest biological levels of prorenin yet detected (close to 1 /Ig protein/ml) occur in gestational sacs in early pregnancy, consistent with a role for the renin-angiotensin system in embryonic development or placentation. (J Clin Endocrinol Metab 75: 906-910,1992)
I?
have all been postulated as sourcesof prorenin in the human amniotic fluid, but the placental chorion laeve is most commonly considered to be the primary source. The role of renin or prorenin in human amniotic fluid is not known. Their presence suggests a possible role in embryonic and fetal development. No information is available regarding the levels of renin and prorenin in gestational fluids (amniotic or chorionic) during the first trimester of pregnancy, when organogenesis and placentation take place. We, therefore, measured prorenin and active renin in amniotic/chorionic fluids obtained from gestational sacsduring the first trimester of pregnancy. We found extraordinarily high concentrations of prorenin (1000 times the normal plasma level) at 3-6 weeks after conception when the major fluid compartment is the chorionic cavity (14) (Fig. 1). hCG was also very high. Much lower levels of both prorenin and hCG were found in fluids aspirated after 8 weeks at a time when the amniotic cavity replaces the chorionic cavity as the major placental fluid compartment. By 16 weeks the levels in amniotic fluid had increased again but not to the same degree as that found very early in gestation.
RORENIN is the biosynthetic precursor of renin, but it is also the major product of renin gene expression in the kidneys and reproductive organs (1). Prorenin can develop reversible intrinsic renin activity in vitro at room temperature and at 4 C (2) and at pH 3.3 (3, 4). In vitro, prorenin can form angiotensin from renin substrate in viva without cleavage of the prosequence (1). Plasma prorenin, which is normally close to 10 times higher than renin, increases lo-fold within 3 weeks after conception and remains elevated until parturition (5, 6). The rise in prorenin early in gestation is of ovarian origin, but the uteroplacental unit may, in part, contribute to circulating prorenin later in gestation (7-9). Amniotic fluid total renin concentration (prorenin plus renin) is reported to range from 100-2500 ng/mL.h (28-700 ng/ Las) (lo-13), averaging about 16 times the plasma concentration found in the second and third trimesters of human pregnancy (12). The major form of the renin in amniotic fluid is prorenin. The fetus, placenta and the uterine decidua Received November 14, 1991. Address all correspondence and requests for reprints to: Joseph Itskovitz (Eldor), M.D., DSc., Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa 31096, Israel. * This work was supported by NIH Grants HL-40152 and HL-18323 SCR. t Present address: Institute di Medicina e Chirurgia, Universita di Napoli, Napoli, Italy.
Subjects Fluids from women during
and Methods
first trimester gestational sacs were obtained from nine selective reduction of multiple pregnancy at 7-12 weeks
906
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 19 November 2015. at 00:18 For personal use only. No other uses without permission. . All rights reserved.
PRORENIN
AND hCG IN GESTATIONAL
SACS
907
renin was measured similarly with the exception that the incubation with Sepharose-bound trypsin was omitted. Prorenin is the difference between active renin and total renin. Prorenin maximum velocity (V,,,) is calculated from the Michaelis-Menten equation using a K, of 2.08 fimol/L. Angiotensinogen was measured as angiotensin I after incubation for 1 h at 37 C and pH 5.7 in the presence of angiotensinase and converting enzyme inhibitors (EDTA and phenylmethylsulfonylfluoride) and excess human renin (17 Goldblatt Unit (GU) /L). hCG was measured using an immunoradiometric assay (hCG MAIAclone from Serono Diagnositics Inc., Norwell, MA). WEEK
Results
FIG. 1. Schematic drawing to show the fluid compartments of the gestational sac at weeks 3, 5, and 8 after conception. The major fluid compartment at week 3 is the chorionic cavity. By week 5 the chorionic cavity is prominent. By week 8 after conception the chorionic cavity is obliterated by fusion of the amnion and chorion, and the amniotic cavity is the major fluid compartment. (From Pansky, B 1982 Review of Medical Embryology. Macmillan Publishing Co., Inc., New York, p 95). and from one patient during laparotomy for twin tubal pregnancy at 5 weeks and 5 days of pregnancy, i.e. 26 days after conception (Table 1). All of these patients had conceived after ovarian stimulation with gonadotropins for the purpose of ovulation induction or in vitro fertilization All gestational sacs in women undergoing selective abortion contained living embryos before aspiration. Early (7-8 weeks) selective reduction guided by transvaginal sonography was carried out by aspiration of the gestational sac and its content (15). Late (lo-12 weeks) first trimester selective abortion was accomplished by fetal intrathoracic injection of KC1 15% solution; a small amount of amniotic fluid was removed before the injection. Transvaginal sonography of the tubal pregnancy before laparotomy, showed two 9-mm gestational sacs containing the yolk sac and embryonic pole without discernible heart activity (could be normal for this stage of pregnancy). One of these gestational sacs was aspirated immediately after removal of the Fallopian tube. The volume aspirated from this sac was 0.3 mL. Second trimester samples were obtained at amniocentesis for chromosomal analysis from 14 women. Third trimester samples were obtained at term from one patient at elective cesarean section, and from two patients at spontaneous labor (4 cm effacement). Patient 12 (Table 1) carried a fetus who had trisomy 21 and cystic hygroma, and patient 14 delivered prematurly at 23 weeks gestation. Patient 21 was treated with aspirin 100 mg/day because of a history of recurrent abortion and had an uneventful pregnancy. Fluid samples were collected into tubes containing K3 ethylenediaminetetraacetate (EDTA), centrifuged to remove cellular elements, and stored at -20
c.
Eormonal
measurements
Gestational sac fluid total renin was measured by enzymatic assay of renin after limited proteolysis with solid phase trypsin (16). The fluid was diluted 1:30 with phosphate buffer (pH 7.4) containing 0.1 mol NaCI, 0.1% Na2 EDTA, 0.5% BSA, and 10 mmol benzamidine-HCl. Sepharose-bound trypsin (250 pg/mL) was added to the samples which were then incubated overnight at 4 C while shaking. After removal of trypsin by centrifugation at 3000 rpm for 30 min at 4 C, the supernatant was assayed for renin activity in the presence of partially purified human angiotensinogen [600 ng/mL (0.46 pmol/L)], and 3 mmol phenylmethylsulfonylfluoride after pH adjustment to 5.7 with 0.276 mol maleic acid. Samples were incubated for 0 and 1 h at 37 C and the formed angiotensin I was measured by RIA. Total renin is the difference in angiotensin I between the 0- and l-h incubation times and is expressed as nanograms per milliliter per hour (or nanograms per L.s). Active
Prorenin was highest in fluids collected before 9 weeks of gestation (i.e. between 26 and 42 days after conception) (Table 1 and Fig. 2). Active renin averaged only 0.2 + 0.1 (&SD)% of total renin. The highest level [140,000 ng/mL.h (39,000 ng/L.s)] was found in the earliest sample, but this was also a tubal pregnancy. The concentration of plasma prorenin in this patient was three orders of magnitude less, 460 ng/mL. h (130 ng/L.s). Four of the sacs (from three patients) had prorenin greater than or equal to 65,000 ng/ mL. h (18,000 “g/L. s) and six others (from five patients) were greater than or equal to 21,000 ng/mL. h (5,800 rig/L. s). At this stage of gestation we have found that plasma prorenin averages about 600 ng/mL. h (170 “g/L. s) in ovarian-stimulated women (6, 7). In sharp contrast, three samples (from two women) that were collected between 10 and 12 weeks of gestation had prorenin levels below 400 ng/mL . h (110 rig/L . s). All other samples were collected during the second to third trimester, between 16 and 41 weeks’ gestation, and in them prorenin ranged from l,lOO-18,000 ng/mL.h (310-5,000 ng/L.s), similar to previously reported values (10, 12, 13); active renin constituted 0.8 + 0.5% of the total renin. No consistent trend was found in the renin substrate concentrations (Table 1). While the three samples collected between 10 and 12 weeks had the lowest concentrations and those collected in the second and third trimester were, on average, higher, there was considerable overlap in the concentrations measured before 9 weeks, between 10 and 12 weeks, and between 16 and 41 weeks of pregnancy. As previously reported (12) all values were an order of magnitude lower than that normally found in maternal plasma. As with prorenin, the highest concentrations of hCG were detected in the seven samples collected before 9 weeks (over 200,000 IU/L) (Table 1 and Fig. 2). In all samples collected after 8 weeks, the hCG concentration was lower than 15,000 IU/L (range 350-14,500 IU/L), that is lower than the levels usually found in plasma at that time (17).
Discussion
This study demonstrates for the first time extraordinarily high concentrations of prorenin in gestational fluids surrounding the human embryo, 26-42 days after conception (40-56 days gestation). hCG concentrations were also very high. In sharp contrast, between 10 and 12 weeks gestation, both prorenin and hCG concentrations were three orders of magnitude lower; even less than that usually found in ma-
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 19 November 2015. at 00:18 For personal use only. No other uses without permission. . All rights reserved.
908 TABLE
ITSKOVITZ 1. Prorenin, Patient
No.
active
renin,
renin
Gestational age (weeks)
substrate,
and hCG
Prorenin
(V,..y
levels
ET AL.
in gestational
[rig/L.
s(ng/mL.h)l
JCE & M. 1992 Vol75.No3
sacs
Active renin [ng/ L.s(ng/mL.h)]
Renin substrate Uw/ml)l
[pmol/
Human CG W/L)
Firsltbtrimester 6 7 7
39,000 22,000 33,000
140,000 80,000 117,000
88 42 53
315 150 190
0.26 0.07 0.05
335 85 65
332,000 272,000
7 7 7 7 7 8
18,000 26,000 5,800 11,000 10,000 8,600
65,000 93,000 21,000 39,000 36,000 31,000
24 24 11 36 42 31
85 86 41 130 150 110
0.04 0.08 0.03 0.14 0.09 0.07
50 110 45 180 120 85
268,000 458,000 234,000
sac 1 sac 2
8 8
10,000 7,800
37,000 28,000
22 6
80 21
0.05 0.17
65 225
303,000 286,000
sac 1 sac 2
10 10 12
50 110 58
1 Cl 40
0.03 0.02 0.03
40 20 40
1,300 630 1,700
16 16 16
890 580
3,200 2,100
7
26 Cl0
0.08 0.03
105 40
4,500 2,900
1,200 1,200 310 3,900 3,600 1,900 720 440 890 5,000
4,400 4,400 1,100 14,000 13,000 6,900 2,600 1,600 3,200 18,000
9 9
Vol. 15, No. 3 Printed in U.S.A.
Highest Concentrations of Prorenin and Human Chorionic Gonadotropin in Gestational Sacs During Early Human Pregnancy* JOSEPH ITSKOVITZ JEAN E. SEALEY
(ELDOR),
SPERANZA
RUBATTU?,
JACOB
LEVRON,
AND
Department of Obstetrics and Gynecology, Rambam Medical Center (J.I., J.L.) and Technion-Israel Institute of Technology, Faculty of Medicine (J.I.), Haifa 31096, Israel; and Cardiovascular Center, The New York Hospital-Cornell University Medical College (S.R., J.E.S.), New York, New York 10021 ABSTRACT Prorenin is not only the biosynthetic precursor of renin; under certain circumstances in vitro prorenin exhibits reversible intrinsic renin activity and can form angiotensin from renin substrate with or without cleavage of the prosequence. Prorenin is the predominant form of renin synthesized by reproductive organs (ovary, chorion laeve of the placenta, uterine decidua). Its plasma concentrations increases lofold throughout pregnancy to lo-100 times that of renin; amniotic fluid prorenin concentration is even higher. No data are available of gestational fluid prorenin concentrations during early pregnancy. For the first 10 weeks there are two gestational cavities; the chorionic cavity then disappears and the smaller amniotic cavity becomes predominant. In this study we measured prorenin, renin, renin substrate and hCG in fluid aspirated from gestational sacs during the first trimester of gestation (predominantly chorionic) and during the second and third trimesters (amniotic). Seventeen patients had amniocentesis during the second or third trimester. Nine patients underwent selective abortion of multiple pregnancy at 7-12 weeks gestation. One patient under-
went surgery at 5% weeks (26 days after conception) for a tubal pregnancy. Second and third trimester amniotic fluid prorenin maximum velocity (V,.,) (16 and 3 sacs, respectively) averaged 6,100 + 1,700 (SD) and 1,930 + 760 ng/mL. h, respectively (i.e. 1,700 and 540 ng/L.s). In gestational fluid collected before 8 weeks, prorenin V,., was lo-fold higher, averaging 62,500 + 40,000 ng/mL. h (17,000 ng/L.s). The concentration was 140,000 ng/mL. h (39,000 ng/L.s) in the 5% week tubal pregnancy. In sharp contrast, at lo-12 weeks gestation (n = 3) prorenin V,., was only 260 + 114 ng/mL. h (72 ng/L.s); human CG was also highest before 8 weeks (276,500 + 110,900 W/L) and lowest at lo-12 weeks (1210 f 540 IU/L) with intermediate levels occurring later in pregnancy. This study shows that the highest biological levels of prorenin yet detected (close to 1 /Ig protein/ml) occur in gestational sacs in early pregnancy, consistent with a role for the renin-angiotensin system in embryonic development or placentation. (J Clin Endocrinol Metab 75: 906-910,1992)
I?
have all been postulated as sourcesof prorenin in the human amniotic fluid, but the placental chorion laeve is most commonly considered to be the primary source. The role of renin or prorenin in human amniotic fluid is not known. Their presence suggests a possible role in embryonic and fetal development. No information is available regarding the levels of renin and prorenin in gestational fluids (amniotic or chorionic) during the first trimester of pregnancy, when organogenesis and placentation take place. We, therefore, measured prorenin and active renin in amniotic/chorionic fluids obtained from gestational sacsduring the first trimester of pregnancy. We found extraordinarily high concentrations of prorenin (1000 times the normal plasma level) at 3-6 weeks after conception when the major fluid compartment is the chorionic cavity (14) (Fig. 1). hCG was also very high. Much lower levels of both prorenin and hCG were found in fluids aspirated after 8 weeks at a time when the amniotic cavity replaces the chorionic cavity as the major placental fluid compartment. By 16 weeks the levels in amniotic fluid had increased again but not to the same degree as that found very early in gestation.
RORENIN is the biosynthetic precursor of renin, but it is also the major product of renin gene expression in the kidneys and reproductive organs (1). Prorenin can develop reversible intrinsic renin activity in vitro at room temperature and at 4 C (2) and at pH 3.3 (3, 4). In vitro, prorenin can form angiotensin from renin substrate in viva without cleavage of the prosequence (1). Plasma prorenin, which is normally close to 10 times higher than renin, increases lo-fold within 3 weeks after conception and remains elevated until parturition (5, 6). The rise in prorenin early in gestation is of ovarian origin, but the uteroplacental unit may, in part, contribute to circulating prorenin later in gestation (7-9). Amniotic fluid total renin concentration (prorenin plus renin) is reported to range from 100-2500 ng/mL.h (28-700 ng/ Las) (lo-13), averaging about 16 times the plasma concentration found in the second and third trimesters of human pregnancy (12). The major form of the renin in amniotic fluid is prorenin. The fetus, placenta and the uterine decidua Received November 14, 1991. Address all correspondence and requests for reprints to: Joseph Itskovitz (Eldor), M.D., DSc., Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa 31096, Israel. * This work was supported by NIH Grants HL-40152 and HL-18323 SCR. t Present address: Institute di Medicina e Chirurgia, Universita di Napoli, Napoli, Italy.
Subjects Fluids from women during
and Methods
first trimester gestational sacs were obtained from nine selective reduction of multiple pregnancy at 7-12 weeks
906
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 19 November 2015. at 00:18 For personal use only. No other uses without permission. . All rights reserved.
PRORENIN
AND hCG IN GESTATIONAL
SACS
907
renin was measured similarly with the exception that the incubation with Sepharose-bound trypsin was omitted. Prorenin is the difference between active renin and total renin. Prorenin maximum velocity (V,,,) is calculated from the Michaelis-Menten equation using a K, of 2.08 fimol/L. Angiotensinogen was measured as angiotensin I after incubation for 1 h at 37 C and pH 5.7 in the presence of angiotensinase and converting enzyme inhibitors (EDTA and phenylmethylsulfonylfluoride) and excess human renin (17 Goldblatt Unit (GU) /L). hCG was measured using an immunoradiometric assay (hCG MAIAclone from Serono Diagnositics Inc., Norwell, MA). WEEK
Results
FIG. 1. Schematic drawing to show the fluid compartments of the gestational sac at weeks 3, 5, and 8 after conception. The major fluid compartment at week 3 is the chorionic cavity. By week 5 the chorionic cavity is prominent. By week 8 after conception the chorionic cavity is obliterated by fusion of the amnion and chorion, and the amniotic cavity is the major fluid compartment. (From Pansky, B 1982 Review of Medical Embryology. Macmillan Publishing Co., Inc., New York, p 95). and from one patient during laparotomy for twin tubal pregnancy at 5 weeks and 5 days of pregnancy, i.e. 26 days after conception (Table 1). All of these patients had conceived after ovarian stimulation with gonadotropins for the purpose of ovulation induction or in vitro fertilization All gestational sacs in women undergoing selective abortion contained living embryos before aspiration. Early (7-8 weeks) selective reduction guided by transvaginal sonography was carried out by aspiration of the gestational sac and its content (15). Late (lo-12 weeks) first trimester selective abortion was accomplished by fetal intrathoracic injection of KC1 15% solution; a small amount of amniotic fluid was removed before the injection. Transvaginal sonography of the tubal pregnancy before laparotomy, showed two 9-mm gestational sacs containing the yolk sac and embryonic pole without discernible heart activity (could be normal for this stage of pregnancy). One of these gestational sacs was aspirated immediately after removal of the Fallopian tube. The volume aspirated from this sac was 0.3 mL. Second trimester samples were obtained at amniocentesis for chromosomal analysis from 14 women. Third trimester samples were obtained at term from one patient at elective cesarean section, and from two patients at spontaneous labor (4 cm effacement). Patient 12 (Table 1) carried a fetus who had trisomy 21 and cystic hygroma, and patient 14 delivered prematurly at 23 weeks gestation. Patient 21 was treated with aspirin 100 mg/day because of a history of recurrent abortion and had an uneventful pregnancy. Fluid samples were collected into tubes containing K3 ethylenediaminetetraacetate (EDTA), centrifuged to remove cellular elements, and stored at -20
c.
Eormonal
measurements
Gestational sac fluid total renin was measured by enzymatic assay of renin after limited proteolysis with solid phase trypsin (16). The fluid was diluted 1:30 with phosphate buffer (pH 7.4) containing 0.1 mol NaCI, 0.1% Na2 EDTA, 0.5% BSA, and 10 mmol benzamidine-HCl. Sepharose-bound trypsin (250 pg/mL) was added to the samples which were then incubated overnight at 4 C while shaking. After removal of trypsin by centrifugation at 3000 rpm for 30 min at 4 C, the supernatant was assayed for renin activity in the presence of partially purified human angiotensinogen [600 ng/mL (0.46 pmol/L)], and 3 mmol phenylmethylsulfonylfluoride after pH adjustment to 5.7 with 0.276 mol maleic acid. Samples were incubated for 0 and 1 h at 37 C and the formed angiotensin I was measured by RIA. Total renin is the difference in angiotensin I between the 0- and l-h incubation times and is expressed as nanograms per milliliter per hour (or nanograms per L.s). Active
Prorenin was highest in fluids collected before 9 weeks of gestation (i.e. between 26 and 42 days after conception) (Table 1 and Fig. 2). Active renin averaged only 0.2 + 0.1 (&SD)% of total renin. The highest level [140,000 ng/mL.h (39,000 ng/L.s)] was found in the earliest sample, but this was also a tubal pregnancy. The concentration of plasma prorenin in this patient was three orders of magnitude less, 460 ng/mL. h (130 ng/L.s). Four of the sacs (from three patients) had prorenin greater than or equal to 65,000 ng/ mL. h (18,000 “g/L. s) and six others (from five patients) were greater than or equal to 21,000 ng/mL. h (5,800 rig/L. s). At this stage of gestation we have found that plasma prorenin averages about 600 ng/mL. h (170 “g/L. s) in ovarian-stimulated women (6, 7). In sharp contrast, three samples (from two women) that were collected between 10 and 12 weeks of gestation had prorenin levels below 400 ng/mL . h (110 rig/L . s). All other samples were collected during the second to third trimester, between 16 and 41 weeks’ gestation, and in them prorenin ranged from l,lOO-18,000 ng/mL.h (310-5,000 ng/L.s), similar to previously reported values (10, 12, 13); active renin constituted 0.8 + 0.5% of the total renin. No consistent trend was found in the renin substrate concentrations (Table 1). While the three samples collected between 10 and 12 weeks had the lowest concentrations and those collected in the second and third trimester were, on average, higher, there was considerable overlap in the concentrations measured before 9 weeks, between 10 and 12 weeks, and between 16 and 41 weeks of pregnancy. As previously reported (12) all values were an order of magnitude lower than that normally found in maternal plasma. As with prorenin, the highest concentrations of hCG were detected in the seven samples collected before 9 weeks (over 200,000 IU/L) (Table 1 and Fig. 2). In all samples collected after 8 weeks, the hCG concentration was lower than 15,000 IU/L (range 350-14,500 IU/L), that is lower than the levels usually found in plasma at that time (17).
Discussion
This study demonstrates for the first time extraordinarily high concentrations of prorenin in gestational fluids surrounding the human embryo, 26-42 days after conception (40-56 days gestation). hCG concentrations were also very high. In sharp contrast, between 10 and 12 weeks gestation, both prorenin and hCG concentrations were three orders of magnitude lower; even less than that usually found in ma-
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 19 November 2015. at 00:18 For personal use only. No other uses without permission. . All rights reserved.
908 TABLE
ITSKOVITZ 1. Prorenin, Patient
No.
active
renin,
renin
Gestational age (weeks)
substrate,
and hCG
Prorenin
(V,..y
levels
ET AL.
in gestational
[rig/L.
s(ng/mL.h)l
JCE & M. 1992 Vol75.No3
sacs
Active renin [ng/ L.s(ng/mL.h)]
Renin substrate Uw/ml)l
[pmol/
Human CG W/L)
Firsltbtrimester 6 7 7
39,000 22,000 33,000
140,000 80,000 117,000
88 42 53
315 150 190
0.26 0.07 0.05
335 85 65
332,000 272,000
7 7 7 7 7 8
18,000 26,000 5,800 11,000 10,000 8,600
65,000 93,000 21,000 39,000 36,000 31,000
24 24 11 36 42 31
85 86 41 130 150 110
0.04 0.08 0.03 0.14 0.09 0.07
50 110 45 180 120 85
268,000 458,000 234,000
sac 1 sac 2
8 8
10,000 7,800
37,000 28,000
22 6
80 21
0.05 0.17
65 225
303,000 286,000
sac 1 sac 2
10 10 12
50 110 58
1 Cl 40
0.03 0.02 0.03
40 20 40
1,300 630 1,700
16 16 16
890 580
3,200 2,100
7
26 Cl0
0.08 0.03
105 40
4,500 2,900
1,200 1,200 310 3,900 3,600 1,900 720 440 890 5,000
4,400 4,400 1,100 14,000 13,000 6,900 2,600 1,600 3,200 18,000
9 9
