Mechanisms of Intrauterine Growth Retardation: Role of Fetal and Maternal Hormones

Gluckman, P. D.; Harding, JE; Oliver, Mark; Liu, L.; Ambler, Geoffrey; Klempt, Martin; Breier, B. H.

doi:10.1007/978-3-642-78217-6_14

“…The high levels of PGH measured from midgestation in human pregnancy (8) are likely to impact on placental metabolism and substrate supply to the fetus, either directly or mediated by IGF-I (2,5,9,10). This is supported by observations that maternal concentrations of total PGH and IGF-I correlate strongly and are decreased in cases of intrauterine growth retardation (IUGR) (5,8,11) and that maternal IGF-I correlates with fetal femur length and birth weight (12).…”

mentioning

confidence: 96%

Placental Growth Hormone (GH), GH-Binding Protein, and Insulin-Like Growth Factor Axis in Normal, Growth-Retarded, and Diabetic Pregnancies: Correlations with Fetal Growth*

McIntyre

¹

,

Serek²,

Crane³

et al. 2000

The Journal of Clinical Endocrinology &Amp; Metabolism

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We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28 -30 weeks gestation (K28) and 36 -38 weeks gestation (K36). The mean concentration (ϮSEM) of total PGH increased significantly from K28 to K36 (30.0 Ϯ 2.2 to 50.7 Ϯ 6.2 ng/mL; n ϭ 40), as did the concentration of free PGH (23.4 Ϯ 2.3 to 43.7 Ϯ 6.0 ng/mL; n ϭ 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P Ͻ 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-3 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGH at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P Ͻ 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P Ͻ 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r ϭ Ϫ0.52; P Ͻ .001), free PGH and total PGH correlated very closely (r ϭ 0.98). The results are consistent with an inhibitory function for GHBP in vivo and support a critical role for placental GH and IGF-I in driving normal fetal growth. (J Clin Endocrinol

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“…(J Clin Endocrinol Metab 85: [1143][1144][1145][1146][1147][1148][1149][1150]2000) L ATE PREGNANCY is a catabolic phase with redistribution of maternal nutrients to support fetal growth (1). Work by Gluckman (2) and others has shown fetal growth to be dependent on maternal substrate supply, and the hormonal mechanisms driving these changes are beginning to be elucidated. Placental GH (PGH) progressively replaces pituitary GH (hGH-N) in the maternal circulation from midgestation (3).…”

mentioning

confidence: 99%

Placental Growth Hormone (GH), GH-Binding Protein, and Insulin-Like Growth Factor Axis in Normal, Growth-Retarded, and Diabetic Pregnancies: Correlations with Fetal Growth

McIntyre¹

2000

Journal of Clinical Endocrinology & Metabolism

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We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28 -30 weeks gestation (K28) and 36 -38 weeks gestation (K36). The mean concentration (ϮSEM) of total PGH increased significantly from K28 to K36 (30.0 Ϯ 2.2 to 50.7 Ϯ 6.2 ng/mL; n ϭ 40), as did the concentration of free PGH (23.4 Ϯ 2.3 to 43.7 Ϯ 6.0 ng/mL; n ϭ 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P Ͻ 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-3 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGH at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P Ͻ 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P Ͻ 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r ϭ Ϫ0.52; P Ͻ .001), free PGH and total PGH correlated very closely (r ϭ 0.98). The results are consistent with an inhibitory function for GHBP in vivo and support a critical role for placental GH and IGF-I in driving normal fetal growth. (J Clin Endocrinol

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Dietary protein concentration correlates in a complex way with glucose metabolism and growth performance in pregnant rats

Jiménez-Gancedo

¹

,

Agis-Torres

²

,

López-Oliva

³

et al. 2004

Domestic Animal Endocrinology

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Mechanisms of Intrauterine Growth Retardation: Role of Fetal and Maternal Hormones

Cited by 5 publications

References 33 publications

Placental Growth Hormone (GH), GH-Binding Protein, and Insulin-Like Growth Factor Axis in Normal, Growth-Retarded, and Diabetic Pregnancies: Correlations with Fetal Growth*

Placental Growth Hormone (GH), GH-Binding Protein, and Insulin-Like Growth Factor Axis in Normal, Growth-Retarded, and Diabetic Pregnancies: Correlations with Fetal Growth*

Placental Growth Hormone (GH), GH-Binding Protein, and Insulin-Like Growth Factor Axis in Normal, Growth-Retarded, and Diabetic Pregnancies: Correlations with Fetal Growth

Dietary protein concentration correlates in a complex way with glucose metabolism and growth performance in pregnant rats

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