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R Barnard

Publications and source records attributed to R Barnard.

At least 19 recordsLinked to original sources
PubMed2002

Placental growth hormone is not suppressed by oral glucose loading in normal human pregnancy.

Placental growth hormone (PGH) progressively replaces pituitary growth hormone in the maternal circulation from mid-gestation onwards in human pregnancy. Our previous investigations have shown that placental growth hormone concentrations correlate well with foetal growth. Despite the apparent correlation between PGH and birthweight, the physiology of its secretion during pregnancy has not been well defined. We investigated the response of maternal serum PGH to oral glucose loading in pregnant women (n = 24) who demonstrated normal glucose tolerance at a mean gestation of 29 weeks. Mean (SEM) fasting PGH concentrations were high (36.9 [6.4] ng/ml). No suppression of PGH was noted at one, two or three hours after a 75 g oral glucose load. Similarly, no changes were noted in growth hormone binding protein or in calculated free PGH over the course of the glucose tolerance test. As expected, insulin concentrations rose sixfold and insulin like growth factor binding protein 1 concentrations fell by 20 % with glucose loading. Correlation analysis showed maternal weight, BMI, fasting serum glucose serum insulin to be significantly correlated with the babies' birthweight. Our results support the proposition that PGH concentrations in maternal serum are not suppressed by oral glucose loading in non-diabetic mothers.

Adult↗
PubMed2001

Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer.

Immunohistochemical staining of human breast tissues, using an antibody against fibroblast growth factor receptor 3 [FGFR-3], showed differences in cellular distribution. Both malignant and non-malignant epithelial cells contained FGFR-3 immunoreactivity, but myoepithelial cells and stroma were negative. The staining pattern in malignant epithelial cells was predominantly nuclear, whereas epithelial cells in normal breast tissue showed both cytoplasmic and nuclear elements. Reverse transcription-polymerase chain reaction (RT-PCR) revealed two isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously described exon-deleted nuclear form of FGFR-3, which were present in both malignant and non-malignant epithelial cells. The higher level of nuclear staining and loss of cytoplasmic staining seen in malignant epithelial cells did not correspond to an increase in expression of the exon-deleted form of FGFR-3, nor to any detectable activating point mutations. Since receptor activation can result in its movement to a perinuclear localization, an alternative explanation for the redistribution of FGFR-3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9). No FGF9 was detected by immunohistochemistry in breast tissues. FGF1, however, is present in the majority of breast cancers and a different tissue distribution of FGF1 was found in breast tissues, showing predominantly nuclear, or a mix of nuclear and cytoplasmic FGFR-3. The difference in FGFR-3 staining patterns may implicate this ligand-receptor pair in breast cancer.

Adult↗
PubMed2001

Growth hormone binding protein in normal and aneuploid pregnancy: a paradoxical decrease in trisomy 18.

OBJECTIVE: To explore whether abnormalities in growth hormone binding protein (GHBP) may underlie the growth restriction associated with fetal aneuploidy. DESIGN: A retrospective casecontrol study. SETTING: Monash Medical Centre. Clayton, Victoria, Australia. POPULATION: Twenty-one trisomy 18, and 30 trisomy 21 pregnancies, and 170 chromosomally normal pregnancies at 15-18 weeks of gestation representing three to five controls per case matched for source, gestation and duration of storage. METHODS: GHBP was measured using a ligand immunofunctional assay RESULTS: In the chromosomally normal pregnancies GHBP levels decreased slightly but significantly across the narrow gestational window studied. Compared with controls, levels of GHBP, expressed as median (95% CI) multiples of the median (MoM). in the trisomy 21 pregnancies were similar, 1.0 (0.92-1.39) MoM and 1.27 (1.04-1.50) MoM, respectively; P = 0.061 (Mann-Whitney U test) but were significantly reduced in the trisomy 18 pregnancies, 0.68 (0.5 1-0.84) MoM: P = 0.0014 (Mann-Whitney U test). CONCLUSIONS: These data suggest that decreased levels of maternal growth hormone binding protein, and by implication growth hormone receptor complement, may underlie the early severe growth restriction that is characteristic of trisomy 18.

Carrier Proteins↗
PubMed2001

Neither the New Zealand genetically hypertensive strain nor Dahl salt-sensitive strain has an A1079T transversion in the alpha1 isoform of the Na(+),K(+)-ATPase gene.

A putative 1079A-->T mutation in the alpha1 isoform of the Na(+), K(+)-ATPase (Atp1a1) gene of the Dahl salt-sensitive rat inbred by John Rapp (SS/Jr) strain was projected to cause a conformation change in the membrane hydrophobic region of the protein product, possibly resulting in hypertension. The existence of the mutation was challenged, but the challenge was apparently rebutted. The New Zealand genetically hypertensive (GH) rat is known to have a blood pressure quantitative trait locus on chromosome 2 containing the gene for the ATPase. Thus, we sought to determine whether the GH rat carried the 1079A-->T transversion. We chose a method, first nucleotide change analysis, that can detect point mutations in a mixed population of polymerase chain reaction (PCR) products, even in the presence of PCR bias, and confirmed our analysis by restriction enzyme digestion of PCR products. To ensure the validity of our analyses, we used site-directed mutagenesis to create positive controls containing the mutation. Surprisingly, we found that neither the GH nor the SS/Jr strain had the A1079T transversion. Indeed, the transversion was not found in any strain tested. As an incidental observation, we have sequenced the intron preceding the exon containing the putative A1079T transversion. Within this intron, a single-base C/T polymorphism was observed at base 132. Our results definitively eliminate the putative A1079T transversion in Atp1a1 as a causative factor underlying hypertension in the GH, spontaneously hypertensive, and SS/Jr rat strains and indicate that alternative candidate genes in the region defined by the chromosome 2 hypertension quantitative trait locus should be examined.

Adenosine Triphosphate↗
PubMed2001

Development of ligase-assisted spacer addition for the measurement of microsatellites.

Conventional methods for detecting differences in microsatellite repeat lengths rely on electrophoretic fractionation on long denaturing polyacrylamide gels, a time-consuming and labor-intensive method. Therefore, there is a need for the development of new and rapid approaches to routinely detect such length polymorphisms. The advent of techniques allowing the coupling of DNA molecules to solid surfaces has provided new prospects in the area of mutation detection. We describe here the development and optimization of the ligase-assisted spacer addition (LASA) method, a novel and rapid procedure based on an ELISA format to measure microsatellite repeat lengths. The LASA assay was successfully applied to a set of 11 bird samples to assess its capabilities as a genotyping method.

Animals↗
PubMed2000

Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: correlations with fetal growth.

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases ofnoninsulin-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 (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 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 < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 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 = -0.52; P < .001), free PGH and total PGH correlated very closely (r = 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.

Adult↗
PubMed1999

Bilin organization in cryptomonad biliproteins.

The bilin organization of three cryptomonad biliproteins (phycocyanins 612 and 645 and phycoerythrin 545) was examined in detail. Two others (phycocyanin 630 and phycoerythrin 566) were studied less extensively. Phycocyanin 645 and phycoerythrin 545 were suggested to have one bilin in each monomeric (alphabeta) unit of the dimer (alpha2beta2) isolated from the others, and the remaining six bilins may be in pairs. One pair was found across the monomer-monomer interface of the protein dimer, and two identical pairs were proposed to be within the monomer protein units. For phycocyanin 612, a major surprise was that a pair of bilins was apparently not found across the monomer-monomer interface, but the remaining bilins were distributed as in the other two cryptomonad proteins. The effect of temperature on the CD spectra of phycocyainin 612 demonstrated that two of the bands (one positive and one negative) behaved identically, which is required if they are coupled. The two lowest-energy CD bands of phycocyanin 612 originated from paired bilins, and the two higher-energy bands were from more isolated bilins. The paired bilins within the protein monomers contained the lowest-energy transition for these biliproteins. Using the bilins as naturally occurring reporter groups, phycocyanin 612 was shown to undergo a reversible change in tertiary structure at 40 degrees C. Protein monomers were shown to be functioning biliproteins. A hypothesis is that the coupled pair of bilins within the monomeric units offers important advantages for efficient energy migration, and other bilins transfer energy to this pair, extending the wavelength range or efficiency of light absorption.

Circular Dichroism↗
PubMed1999

Increased expression of fibroblast growth factor 8 in human breast cancer.

Fibroblast growth factor 8 (FGF8) is an important developmental protein which is oncogenic and able to cooperate with wnt-1 to produce mouse mammary carcinoma. The level of expression of FGF8 mRNA was measured in 68 breast cancers and 24 non-malignant breast tissues. Elevated levels of FGF8 mRNA were found in malignant compared to non-malignant breast tissues with significantly more malignant tissues expressing FGF8 (P=0.019) at significantly higher levels (P=0.031). In situ hybridization of breast cancer tissues and analysis of purified populations of normal epithelial cells and breast cancer cell lines showed that malignant epithelial cells expressed FGF8 mRNA at high levels compared to non-malignant epithelial and myoepithelial cells and fibroblasts. Although two of the receptors which FGF8 binds to (FGFR2-IIIc, FGFR3-IIIc) are not expressed in breast cancer cells, an autocrine activation loop is possible since expression of fibroblast growth factor receptor (FGFR) 4 and FGFR1 are retained in malignant epithelial cells. This is the first member of the FGF family to have increased expression in breast cancer and a potential autocrine role in its progression.

Adult↗
PubMed1999

The significance of Erb-b2 immunostaining in cervical cancer.

OBJECTIVE: The aim of this study was to assess the relationship between survival and erb-b2 immunohistochemical staining in patients with early stage cervical carcinoma. METHODS: Archival specimens for 126 patients with stage IB/IIA cervical carcinoma treated with radical hysterectomy and bilateral pelvic node dissection (RH-BPND) were retrieved and submitted to immunohistochemistry for ERBB2 expression. The association between positive results and poor survival was assessed in a multivariate analysis. RESULTS: Erb-b2 immunostaining was significantly associated with poor survival (P = 0.0284) but less so than parametrial extension (P = 0.0014) and nodal disease (P = 0.0106). Tumor type (squamous/adenosquamous/adenocarcinoma) and the status of surgical margins were not significantly associated with survival. CONCLUSIONS: These results supported further investigations of ERBB2 expression as a marker of high-risk disease in patients treated with RH-BPND.

Adenocarcinoma↗
PubMed1999

Bcl-2 genes and growth factors in the pathology of ischaemic acute renal failure.

For the past decade, an attempt has been made by many research groups to define the roles of the growing number of Bcl-2 gene family proteins in the apoptotic process. The Bcl-2 family consists of pro-apoptotic (or cell death) and anti-apoptotic (or cell survival) genes and it is the balance in expression between these gene lineages that may determine the death or survival of a cell. The majority of studies have analysed the role/s of the Bcl-2 genes in cancer development. Equally important is their role in normal tissue development, homeostasis and non-cancer disease states. Bcl-2 is crucial for normal development in the kidney, with a deficiency in Bcl-2 producing such malformation that renal failure and death result. As a corollary, its role in renal disease states in the adult has been sought. Ischaemia is one of the most common causes of both acute and chronic renal failure. The section of the kidney that is most susceptible to ischaemic damage is the outer zone of the outer medulla. Within this zone the proximal tubules are most sensitive and often die by necrosis or desquamate. In the distal nephron, apoptosis is the more common form of cell death. Recent results from our laboratory have indicated that ischaemia-induced acute renal failure is associated with up-regulation of two anti-apoptotic Bcl-2 proteins (Bcl-2 and Bcl-XL) in the damaged distal tubule and occasional up-regulation of Bax in the proximal tubule. The distal tubule is a known reservoir for several growth factors important to renal growth and repair, such as insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF). One of the likely possibilities for the anti-cell death action of the Bcl-2 genes is that the protected distal cells may be able to produce growth factors that have a further reparative or protective role via an autocrine mechanism in the distal segment and a paracrine mechanism in the proximal cells. Both EGF and IGF-1 are also up-regulated in the surviving distal tubules and are detected in the surviving proximal tubules, where these growth factors are not usually synthesized. As a result, we have been using in vitro methods to test: (i) the relative sensitivities of renal distal and proximal epithelial cell populations to injury caused by mechanisms known to act in ischaemia-reperfusion; (ii) whether a Bcl-2 anti-apoptotic mechanism acts in these cells; and (iii) whether an autocrine and/or paracrine growth factor mechanism is initiated. The following review discusses the background to these studies as well as some of our preliminary results.

Acute Kidney Injury↗
PubMed1999

Growth hormone binding protein correlates strongly with leptin and percentage body fat in GH-deficient adults, is increased by GH replacement but does not predict IGF-I response.

GH-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor (GHR) and has been shown to be closely related to body fat. This study aimed to examine the inter-relationship between GHBP, leptin and body fat, and to test the hypothesis that GHBP is modified by GH replacement in GH-deficient adults and predicts IGF-I response. Twenty adults, mean age 47 years (range 20-69) with proven GH deficiency were randomly allocated to either GH (up to 0.25 U/kg/week in daily doses) or placebo for 3 months before cross-over to the opposite treatment. Plasma GHBP and leptin were measured at baseline and 2, 4, 8 and 12 weeks after each treatment. Whole body composition was measured at baseline by dual-energy X-ray absorptiometry (DEXA). There was a strong correlation between baseline leptin and GHBP (r = 0.88, P < 0.0001) and between baseline GHBP and percentage body fat, (r = 0.83, P < 0.0001). Mean GHBP levels were higher on GH compared with placebo, 1.53 +/- 0.28 vs 1.41 +/- 0.25nM, P = 0.049. There was no correlation between baseline IGF-I and GHBP (r = -0.049, P = 0.84), and GHBP did not predict IGF-I response to GH replacement. The close inter-relationship between GHBP, leptin and body fat suggests a possible role for GHBP in the regulation of body composition. GHBP is increased by GH replacement in GH-deficient adults, but does not predict biochemical response to GH replacement.

Absorptiometry, Photon↗
PubMed1999

Administration of growth hormone or IGF-I to pregnant rats on a reduced diet throughout pregnancy does not prevent fetal intrauterine growth retardation and elevated blood pressure in adult offspring.

Increasing evidence from human epidemiological studies suggests that poor growth before birth is associated with postnatal growth retardation and the development of cardiovascular disease in adulthood. We have shown previously that nutritional deprivation in the pregnant rat leads to intrauterine growth retardation (IUGR), postnatal growth failure, changes in the endocrine parameters of the somatotrophic axis, and to increased blood pressure in later life. In the present study, we investigated whether administration of insulin-like growth factor-I (IGF-I) or bovine growth hormone (GH) during pregnancy could prevent IUGR and/or alter long-term outcome. Dams from day 1 of pregnancy throughout gestation received a diet of ad libitum available food or a restricted dietary intake of 30% of ad libitum fed dams. From day 10 of gestation, dams were treated for 10 days with three times daily subcutaneous injections of saline (100 microl), IGF-I (2 micrograms/g body weight) or GH (2 micrograms/g body weight). Maternal weight gain was significantly increased (P<0.001) in ad libitum fed dams treated with GH, (98.9+/-4.73 g) compared with the IGF-I (80.5+/-2.17 g) and saline-treated (70.7+/-2.65 g) groups. There was a small increase in maternal weight gain (P<0.06) in 30% ad libitum fed dams following GH (16.3+/-2.47 g) and IGF-I (15.8+/-1.97 g) treatment compared with saline (9.2+/-1.96 g). Whole spleen, kidney and carcass weights were significantly (P<0.05) increased in ad libitum fed and 30% ad libitum fed dams with GH treatment. Circulating IGF-I was significantly increased (P<0.001) in ad libitum fed dams with both IGF-I (369.6+/-32.33 ng/ml) and GH (457.9+/-33.32 ng/ml) compared with saline treatment (211.7+/-14.02 ng/ml), and with GH (223.4+/-23.72 ng/ml) compared with saline treatment (112.0+/-7.33 ng/ml) in 30% ad libitum fed dams. Circulating GH binding protein (GHBP) levels were significantly reduced (P<0.05) in GH-treated (299.1+/-51.54 ng/ml) compared with saline-treated (503.9+/-62.43 ng/ml) ad libitum fed dams, but were not altered in 30% ad libitum fed dams. There was no significant effect of either IGF-I or GH treatment on fetal weight, placental weight, fetal organ weights or circulating IGF-I levels in both ad libitum fed and 30% ad libitum fed fetuses. Offspring of 30% ad libitum fed dams remained significantly growth retarded postnatally and showed elevated blood pressure in later life. The increased maternal weight gain following IGF-I or GH administration, without an effect on fetal and placental weights, suggests a modification in the mode of maternal nutrient repartitioning during mid to late pregnancy at the expense of the fetus.

Animals↗
PubMed1998

Analysis and application of an equilibrium model for in vitro bioassay systems with three components: receptor, hormone and hormone-binding-protein.

A simple theoretical framework is presented for bioassay studies using three component in vitro systems. An equilibrium model is used to derive equations useful for predicting changes in biological response after addition of hormone-binding-protein or as a consequence of increased hormone affinity. Sets of possible solutions for receptor occupancy and binding protein occupancy are found for typical values of receptor and binding protein affinity constants. Unique equilibrium solutions are dictated by the initial condition of total hormone concentration. According to the occupancy theory of drug action, increasing the affinity of a hormone for its receptor will result in a proportional increase in biological potency. However, the three component model predicts that the magnitude of increase in biological potency will be a small fraction of the proportional increase in affinity. With typical initial conditions a two-fold increase in hormone affinity for its receptor is predicted to result in only a 33% increase in biological response. Under the same conditions an 11-fold increase in hormone affinity for receptor would be needed to produce a two-fold increase in biological potency. Some currently used bioassay systems may be unrecognized three component systems and gross errors in biopotency estimates will result if the effect of binding protein is not calculated. An algorithm derived from the three component model is used to predict changes in biological response after addition of binding protein to in vitro systems. The algorithm is tested by application to a published data set from an experimental study in an in vitro system (Lim et al., 1990, Endocrinology 127, 1287-1291). Predicted changes show good agreement (within 8%) with experimental observations.

Animals↗
PubMed1998

Expression of growth hormone receptors by lymphocyte subpopulations in the human tonsil.

The ability of human tonsillar lymphoid cells to express growth hormone receptor (hGH-N-R) was analyzed by flow cytometry. FITC-coupled recombinant human growth hormone (hGH-N) was used to reveal the receptors, in combination with phenotype markers. Unlike T cells, tonsillar B cells constitutively express the hGH-N receptor. Quiescent cells separated from activated cells by Percoll-gradient centrifugation bear fewer receptors than activated ones. Activated T cells express hGH-N-R, but the typical germinal centre CD4+ CD57+ T cells do not. These latter thus appear not to be fully activated. Inside the lymph follicles, the germinal centre CD38+ B-cell population and the mantle-zone CD39+ B-cell population display similar levels of hGH-N-R expression, but receptor density is lower on dividing dark-zone CD38+ CD10+ B cells. Different lymphoid-cell populations thus differ markedly in their ability to express the growth hormone receptor, in relation notably to their activation status. This highlights the link between the neuroendocrine system and the active immune defense.

B-Lymphocyte Subsets↗
PubMed1998

PCR bias toward the wild-type k-ras and p53 sequences: implications for PCR detection of mutations and cancer diagnosis.

PCR-based cancer diagnosis requires detection of rare mutations in k-ras, p53 or other genes. The assumption has been that mutant and wild-type sequences amplify with near equal efficiency, so that they are eventually present in proportions representative of the starting material. Work on factor IX suggests that this assumption is invalid for one case of near-sequence identity. To test the generality of this phenomenon and its relevance to cancer diagnosis, primers distant from point mutations in p53 and k-ras were used to amplify wild-type and mutant sequences from these genes. A substantial bias against PCR amplification of mutants was observed for two regions of the p53 gene and one region of k-ras. For k-ras and p53, bias was observed when the wild-type and mutant sequences were amplified separately or when mixed in equal proportions before PCR. Bias was present with proofreading and non-proofreading polymerases. Mutant and wild-type segments of the factor V, cystic fibrosis transmembrane conductance regulator and prothrombin genes were amplified and did not exhibit PCR bias. Therefore, the assumption of equal PCR efficiency for point mutant and wild-type sequences is invalid in several systems. Quantitative or diagnostic PCR will require validation for each locus, and enrichment strategies may be needed to optimize detection of mutants.

Base Sequence↗
PubMed1997

Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer.

Monoclonal antibodies against two epitopes of FGFR-1 have been used to investigate FGFR-1 expression in the normal and neoplastic human breast. Different forms are detected in the different cell types constituting the normal breast. Moreover, breast cancer cells lack one form of FGFR-1. Western blot analysis showed 115-kDa and 106-kDa forms of FGFR-1 within the human breast. The 115-kDa band corresponds to the beta form of FGFR-1, whereas the 106-kDa band is truncated at the carboxyl terminus. The 106-kDa form of FGFR-1 is the major form present in breast fibroblasts and myoepithelial cells, whereas epithelial cells contain equal amounts of the 115-kDa and 106-kDa forms. Breast cancer cells, however, appear to contain only the 115-kDa form of FGFR-1. This expression pattern is reflected in malignant and non-malignant tissue samples. Using reverse transcription polymerase chain reaction (RT-PCR) analysis, we have shown that the 106-kDa FGFR-1 isoform is not the previously described alpha 2 receptor that arises from a 25-base pair insertion in the second kinase domain. It is probable that the 106-kDa FGFR-1 has different signalling properties to the full-length receptor, having lost at least one tyrosine at amino acid 766, which is required for phospholipase C activation. This form of FGFR-1 appears to be lost in all breast cancer cells analysed and its absence may have a bearing on malignancy.

Amino Acid Sequence↗
PubMed1997

Growth hormone-binding protein in normal and pathologic gestation: correlations with maternal diabetes and fetal growth.

To date, measurements of GH-binding protein (GHBP) during human pregnancy have been carried out using assays susceptible to interference by the elevated levels of human placental GH typical of late gestation. We recruited a large cohort of pregnant women (n = 140) for serial measurements of GHBP and used the ligand immunofunctional assay for GHBP. For normal gravidas, GHBP levels fell throughout gestation. Mean levels were 1.07 nmol/L (SE = 0.18) in the first trimester, 0.90 nmol/L (SE = 0.08) at 18-20 weeks, 0.73 nmol/L (SE = 0.05) at 28-30 weeks, and 0.62 nmol/L (SE = 0.06) at 36-38 weeks. GHBP levels in the first trimester correlated significantly with maternal body mass index (r = 0.58; P < 0.01). GHBP levels in pregnancies complicated by noninsulin-dependent diabetes mellitus (NIDDM) were substantially elevated at all gestational ages. The mean value in the first quarter (2.29 nmol/L) was more than double the normal mean (P < 0.01). In contrast, patients with insulin-dependent diabetes mellitus (IDDM) showed reduced GHBP concentrations at 36-38 weeks. The correlation between body mass index and GHBP is consistent with a metabolic role for GHBP during pregnancy, as is the dramatic elevation in GHBP observed in cases of NIDDM. At 36 weeks gestation, GHBP was significantly elevated (P < 0.01) in those women whose neonates had low birth weight (< 10th percentile). In early gestation (< 14 weeks), GHBP tended to be higher in women whose fetuses were designated to be at risk of intrauterine growth retardation (1.39 nmol/L; n = 4; compared with 1.07 nmol/L in normals), but this did not reach statistical significance. Although both NIDDM and IDDM pregnancies are at risk of fetal macrosomia, their GHBP concentrations are markedly divergent. This paradox and the roles of glucose and insulin in the regulation of GHBP during gestation warrant further investigation.

Carrier Proteins↗