0021-972X/78/0047-0695$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society
Vol. 47, No. 3 Printed in U.S.A.
SERUM IMMUNOREACTIVE SOMATOMEDIN-C IS ELEVATED LATE IN PREGNANCY1 R.W. FURLANETTO2, L.E. UNDERWOOD, J.J. VAN WYK AND S. HANDWERGER Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill and Department of Pediatrics, Duke University Medical Center, Durham, N.C. ABSTRACT. The concentrations of immunoreactive somatomedin-C (Sm-C) in the sera of women with uncomplicated pregnancies were found to be progressively higher as the duration of gestation increased. Between 19 and 42 weeks of gestation, there was a significant correlation between serum Sm-C concentration and duration of gestation. A striking decline in Sm-C was observed following delivery. While the data are too preliminary to elucide the mechanisms for the raised Sm-C, the concurrent increase in Sm-C and human placental lactogen (hPL) raises the possibility that hPL may mediate the increment in Sm-C.
Studies of the serum concentrations of the somatomedins during pregnancy are limited. Using a competitive membrane binding (CMB) assay, Megyesi, et_ al. reported that the levels of one of the somatomedins, nonsuppressible insulin-like activity, were elevated in 5 of 6 pregnant subjects (1), but the stage of pregnancy of these subjects was not stated. Bala, et al., have observed that bioassayable Sm is low before 24 weeks gestation, normal at 25-28 weeks, falls to low levels by 36 weeks, and returns to normal by delivery at term (2). The recent development of a sensitive radioimmunoassay has made it possible to measure the concentration of Sm-C with greater specificity than has been afforded previously by either CMB assays or by bioassays (3). In the bioassay there are inhibitors of Sm's action and in the CMB assay there are substances which compete with radiolabeled Sm-C for membrane binding sites. The latter phenomenon was observed by Chochinov, et^ a^. in studies of amniotic fluid (4-5). In this report, the serum concentrations of Sm-C are assessed in 50 women during pregnancy
Submitted 29 December, 1977. "Present Address: Department of Pediatrics, University of Texas, Galveston.
and in the postpartum period and the results are compared with hPL concentrations in the same subjects. MATERIALS AND METHODS Serum samples were obtained from 53 pregnant and 6 postpartum women who were attending the obstetrical clinics of the North Carolina Memorial Hospital. With the exception of 5 subjects who were receiving dicyclomine and doxylamine or promethazine for nausea, selection of pregnant subjects was limited to those whose pregnancies were uncomplicated and who were taking no medications other than prenatal vitamins. Duration of the pregnancies were estimated from the time of the last menstrual period and ranged between 5 1/2 - 42 weeks. Five of the postpartum samples were obtained within 72 hours of delivery; the 6th was obtained at 7 weeks postpartum. Two of the 6 postpartum women received high dosages of estrogen following delivery and were not breast feeding. Sm was also determined in 41 normal, nonpregnant women of childbearing age (median age 25 years) who were in the follicular phase of their menstrual cycle as determined by retrospective analysis of basal body temperature measurements. No subject was sampled on more than one occasion. Most samples were obtained between 0900 and 1300.
695
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 12 November 2015. at 22:15 For personal use only. No other uses without permission. . All rights reserved.
JCE&M • 1978 Vol 47 • No 3
RAPID COMMUNICATIONS
Blood was allowed to clot, cells and serum were separated by centrifugation and the serum was stored at -20°C until assayed. Sm-C concentrations were measured by radioimmunoassay as previously described (3). The Sm reference standard (MUC) is a human serum pool obtained from 3 health adult male volunteers and arbitrarily defined as containing 1 U of Sm activity/ml. The potency of this standard has been observed to consistently fall below the mean activity for larger groups of normal subjects. Human placental lactogen was measured by radioimmunoassay (6) .
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RESULTS The mean Sm-C concentration for the 41 nonpregnant, control women was 1.47 + 0.53 U/ml (1 SD). In the 11 women sampled between 5 and 18 weeks of gestation, the mean Sm-C was 0.91 + 0.22 U/ml (Figure 1; top panel). This is significantly less (p
Vol. 47, No. 3 Printed in U.S.A.
SERUM IMMUNOREACTIVE SOMATOMEDIN-C IS ELEVATED LATE IN PREGNANCY1 R.W. FURLANETTO2, L.E. UNDERWOOD, J.J. VAN WYK AND S. HANDWERGER Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill and Department of Pediatrics, Duke University Medical Center, Durham, N.C. ABSTRACT. The concentrations of immunoreactive somatomedin-C (Sm-C) in the sera of women with uncomplicated pregnancies were found to be progressively higher as the duration of gestation increased. Between 19 and 42 weeks of gestation, there was a significant correlation between serum Sm-C concentration and duration of gestation. A striking decline in Sm-C was observed following delivery. While the data are too preliminary to elucide the mechanisms for the raised Sm-C, the concurrent increase in Sm-C and human placental lactogen (hPL) raises the possibility that hPL may mediate the increment in Sm-C.
Studies of the serum concentrations of the somatomedins during pregnancy are limited. Using a competitive membrane binding (CMB) assay, Megyesi, et_ al. reported that the levels of one of the somatomedins, nonsuppressible insulin-like activity, were elevated in 5 of 6 pregnant subjects (1), but the stage of pregnancy of these subjects was not stated. Bala, et al., have observed that bioassayable Sm is low before 24 weeks gestation, normal at 25-28 weeks, falls to low levels by 36 weeks, and returns to normal by delivery at term (2). The recent development of a sensitive radioimmunoassay has made it possible to measure the concentration of Sm-C with greater specificity than has been afforded previously by either CMB assays or by bioassays (3). In the bioassay there are inhibitors of Sm's action and in the CMB assay there are substances which compete with radiolabeled Sm-C for membrane binding sites. The latter phenomenon was observed by Chochinov, et^ a^. in studies of amniotic fluid (4-5). In this report, the serum concentrations of Sm-C are assessed in 50 women during pregnancy
Submitted 29 December, 1977. "Present Address: Department of Pediatrics, University of Texas, Galveston.
and in the postpartum period and the results are compared with hPL concentrations in the same subjects. MATERIALS AND METHODS Serum samples were obtained from 53 pregnant and 6 postpartum women who were attending the obstetrical clinics of the North Carolina Memorial Hospital. With the exception of 5 subjects who were receiving dicyclomine and doxylamine or promethazine for nausea, selection of pregnant subjects was limited to those whose pregnancies were uncomplicated and who were taking no medications other than prenatal vitamins. Duration of the pregnancies were estimated from the time of the last menstrual period and ranged between 5 1/2 - 42 weeks. Five of the postpartum samples were obtained within 72 hours of delivery; the 6th was obtained at 7 weeks postpartum. Two of the 6 postpartum women received high dosages of estrogen following delivery and were not breast feeding. Sm was also determined in 41 normal, nonpregnant women of childbearing age (median age 25 years) who were in the follicular phase of their menstrual cycle as determined by retrospective analysis of basal body temperature measurements. No subject was sampled on more than one occasion. Most samples were obtained between 0900 and 1300.
695
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 12 November 2015. at 22:15 For personal use only. No other uses without permission. . All rights reserved.
JCE&M • 1978 Vol 47 • No 3
RAPID COMMUNICATIONS
Blood was allowed to clot, cells and serum were separated by centrifugation and the serum was stored at -20°C until assayed. Sm-C concentrations were measured by radioimmunoassay as previously described (3). The Sm reference standard (MUC) is a human serum pool obtained from 3 health adult male volunteers and arbitrarily defined as containing 1 U of Sm activity/ml. The potency of this standard has been observed to consistently fall below the mean activity for larger groups of normal subjects. Human placental lactogen was measured by radioimmunoassay (6) .
3.5
30
I
•
Units/
696
1^
o
? 2.0 a UJ
Z
1
•
5
v
•
10 •
0.5
*
•*
•
•
RESULTS The mean Sm-C concentration for the 41 nonpregnant, control women was 1.47 + 0.53 U/ml (1 SD). In the 11 women sampled between 5 and 18 weeks of gestation, the mean Sm-C was 0.91 + 0.22 U/ml (Figure 1; top panel). This is significantly less (p
