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Biomedical subjects

G D Braunstein

Publications and source records attributed to G D Braunstein.

At least 19 recordsLinked to original sources
PubMed1992

Do thyroid function tests independently predict survival in the critically ill?

We studied the ability of thyroid function tests to predict hospital survival in 116 critically ill patients and compared the results with independent predictions of survival made by critical care physicians. Eleven patients (9.5%) had clinically unsuspected hypothyroidism and were less likely to survive (p = 0.03). In patients critically ill with nonthyroidal disease, low T3, low FT3I, low T4, low FT4I, high TSH, and high T3U levels each showed significant correlation with nonsurvival (all p less than 0.02). Of these, however, only low T3 (p less than 0.001) and high TSH (p = 0.016) showed significant independent prediction of nonsurvival, and only low T3 (p = 0.011) added any significant independent prediction of nonsurvival beyond that made clinically by the group of critical care physicians.

Critical Illness↗
PubMed1992

Somatostatin analog induces insulin-like growth factor binding protein-1 (IGFBP-1) expression in human hepatoma cells.

As the somatostatin analog octreotide suppresses pituitary GH secretion and circulating IGF-1 levels, we examined its effects on human hepatoma (hep G2) cells which selectively express IGFBP-1. Octreotide (60 nM) stimulated IGFBP-1 up to 4.1-fold (p < 0.001 after 24 hrs). Induction of IGFBP-1 was first detectable after 12 hrs of 6 nM octreotide (1.5-fold, p < 0.03), and was confirmed by ligand blotting. Cholera toxin and forskolin induced IGFBP-1 independently and were also additive with octreotide. IGFBP-1 mRNA expression was induced 2.7-fold by octreotide. Thus, octreotide induces basal and stimulated IGFBP-1 in hepatocytes independently of insulin and GH. As IGFBP-1 may regulate peripheral IGF-1 action, induction of IGFBP-1 represents a novel pituitary-independent mechanism for octreotide action.

Blotting, Northern↗
PubMed1992

Octreotide stimulates insulin-like growth factor-binding protein-1: a potential pituitary-independent mechanism for drug action.

As the long-acting somatostatin analog octreotide attenuates polypeptide hormone hypersecretion, it has recently been used to effectively treat acromegaly and gastrointestinal carcinoid tumors. Most growth-promoting actions of GH are mediated by insulin-like growth factor-I (IGF-I), which circulates complexed with multiple binding proteins (IGFBPs). IGFBP-1, a nonglycosylated peptide, competes with the IGF-I receptor for ligand binding and also regulates IGF action. To examine GH-independent mechanisms for octreotide regulation of the GH axis, circulating levels of IGFBP-1 were measured hourly after sc octreotide or saline administration in normal and GH-deficient adults. As IGFBP-1 is inhibited by insulin and GH, the dynamic pattern of alterations in GH and insulin levels was also assessed. After octreotide (100 micrograms) administration to 10 normal subjects, mean IGFBP-1 concentrations were stimulated from 23 +/- 4 to 72 +/- 18 micrograms/L (P < 0.007 vs. saline) after 2 h. Maximal induction of IGFBP-1 levels occurred after 3 h (325 +/- 115 micrograms/L; P < 0.02 vs. saline) and remained elevated (P < 0.005) for 6 h. IGFBP-1 was induced by octreotide in all subjects and was confirmed by Western ligand blotting. Insulin and GH levels preceding the rise in IGFBP-1 were unaltered by octreotide. Octreotide stimulated IGFBP-1 5-fold during a sustained fast in 4 normal subjects, despite equally suppressed insulin levels in both saline- and octreotide-treated groups. In 4 GH-deficient adults, IGFBP-1 levels were stimulated by octreotide from 16 +/- 3 to 146 +/- 36 and 154 +/- 28 micrograms/L after 3 and 4 h, respectively. In conclusion, the somatostatin analog octreotide induces IGFBP-1 independently of GH and insulin. As IGFBP-1 regulates the action of IGF-I, octreotide stimulation of IGFBPs may represent an additional pharmacological mechanism for attenuating the GH-IGF-I axis.

Adolescent↗
PubMed1991

Effects of anabolic-androgenic steroids on muscular strength.

OBJECTIVE: To assess the effects of anabolic-androgenic steroids on human muscle strength. DATA SOURCES: A MEDLINE search for the period from January 1966 to April 1990, supplemented by manual searches of previous reviews, produced 30 studies in which subjects received more than one dose of the study steroid and in which changes in muscular strength were measured. STUDY SELECTION: Of the 30 studies, 14 were not included in the detailed data summary because they did not use a placebo control, did not randomize subjects to groups, or did not make objective strength measurements, or because percent change in strength data could not be abstracted. DATA EXTRACTION: Details of study design, reporting of results, and the adequacy and correctness of statistical methods were tabulated. Percent improvement in strength for the largest muscle group studied was computed, using the difference between results for the placebo and for the steroid-treated groups. DATA SYNTHESIS: Previously trained athletes show slightly greater improvements in strength in the anabolic-androgenic steroid-treated group than in the placebo group, with a median difference of 5% across the nine studies (range, 1.2% to 18.7%). A meta-analysis of the three studies with enough information to compute effect size showed a mean difference of 1.0 standard deviations (95% CI, 0.49 to 1.5). However, the poor overall quality of the studies in terms of design, sample size, and analysis; the lack of a dose-response effect across the narrow range of dosages tested; and the tendency for differences to be smaller in the larger studies throw these results into question. No evidence was found to support enhanced muscle strength with steroid use in eight studies in untrained normal volunteers. CONCLUSIONS: Anabolic steroids may slightly enhance muscle strength in previously trained athletes. No firm conclusion is possible concerning the efficacy of anabolic steroids in enhancing overall athletic performance. Results for the low steroid dosages studied in the published reports cannot be generalized to steroid-using athletes taking megadose regimens.

Anabolic Agents↗
PubMed1991

Pediatric germ cell and human chorionic gonadotropin-producing tumors. Clinical and laboratory features.

Germ cell tumors may cause various aberrations in pubertal development. In prepubertal boys, these tumors may secrete human chorionic gonadotropin, resulting in precocious puberty. Human chorionic gonadotropin and alpha-fetoprotein are both useful as germ cell tumor markers in the diagnosis and detection of recurrence. Pregnancy-specific beta 1-glycoprotein, another oncoplacental antigen, has been used as a tumor marker for trophoblastic neoplasms, but not previously for human chorionic gonadotropin-producing tumors associated with precocious puberty. Patients with germ cell tumors may also have abnormal karyotypes. Herein, we describe six male pediatric patients with germ cell tumors and pubertal derangements seen during an 8-year period. We confirm the high incidence of associated sexual precocity, the usefulness of alpha-fetoprotein, human chorionic gonadotropin, and pregnancy-specific beta 1-glycoprotein as tumor markers in the diagnosis and follow-up of these patients, and the occurrence of sex chromosomal abnormalities.

Adolescent↗
PubMed1991

Decidua produces a protein that inhibits choriogonadotrophin release from human trophoblasts.

To test the hypothesis that uterine decidua may modulate trophoblast function, trophoblasts and decidual cells were isolated from term placentas by enzymatic digestion and Percoll gradient centrifugation. Placental trophoblasts were cocultured with decidual cells and trophoblasts or JEG-3 choriocarcinoma cells were incubated with medium conditioned by decidual cells (DCM) for 72-96 h. In cocultures decidual cells inhibited choriogonadotropin (hCG) release from trophoblasts by 75% in comparison with controls (P less than 0.001). The DCM contained a factor that markedly inhibited hCG release from trophoblasts and JEG cells in vitro compared with controls. The inhibitory effect of the factor on hCG release was dose dependent, and could be eliminated by boiling the DCM for 30 min or proteolytic enzyme treatment. Ultrafiltration and Sephadex G-50 fractionation of the DCM indicated that the apparent molecular mass was 7,000-10,000 D. DCM also inhibited the stimulatory effect of exogenous cAMP on hCG secretion by JEG-3 cells, suggesting that DCM may interfere with activation of the cAMP-dependent protein kinases or transcription of hCG genes. These results suggest that the release of trophoblast hCG is under local paracrine control, regulated in part by a protein released by decidual cells.

Cells, Cultured↗
PubMed1991

Retinoic acid stimulates placental hormone secretion by choriocarcinoma cell lines in vitro.

Retinoic acid (RA), an active metabolite of vitamin A, is an important mediator of cellular differentiation and has been shown to stimulate human CG (hCG) secretion by JEG-3 choriocarcinoma cells in vitro. In order to determine whether RA stimulates the hCG secretion by other trophoblastic cell lines, we evaluated the effect of RA on hCG, hCG-alpha subunit (hCG-alpha), and progesterone secretion in three choriocarcinoma cell lines: JEG-3, JAR, and BeWo. RA stimulated hCG and hCG-alpha secretion in a dose-dependent fashion by each of the three cell lines. The time required to give a statistically significant increment of hCG and hCG-alpha over control cells was 48 h. The addition RA to cholera toxin (10 micrograms/ml) resulted in an additive or synergistic stimulation of hCG and hCG-alpha secretion by the three cell lines. Cycloheximide (1 microM) abolished the effect of RA on hCG and hCG-alpha secretion in the BeWo cell line. Progesterone secretion in response to RA was inconsistent. Progesterone secretion by both JEG-3 and BeWo cell lines were stimulated at high concentrations of RA (1 x 10(-6], whereas progesterone secretion by JAR cells was not stimulated. Intracellular levels of cAMP were not affected by RA treatment in the JEG and JAR cells. In the dosages used, RA did not significantly alter cell number in any of the cell lines. RA in physiologic concentrations stimulates hCG and hCG-alpha secretion by three choriocarcinoma cell lines in vitro. Whether RA is a physiologic mediator of placental hormone production is unknown.

Cell Line↗
PubMed1991

Insulin stimulates synthesis and release of human chorionic gonadotropin by choriocarcinoma cell lines.

Recent studies have shown that insulin regulates placental lactogen, progesterone, and estrogen production from human trophoblast cells. This study was performed to examine whether insulin also regulates the production of hCG by this type of cell. After 24-36 h of preincubation, JEG-3 and JAR cells (2-3 x 10(5) cells/ml.well) or human term trophoblast cells (1 x 10(6) cells/ml.well) were exposed to the test hormone in serum-free Dulbecco's Modified Eagle's Medium for 24-96 h. Secretion of hCG from JEG-3 cells was stimulated by human insulin, human proinsulin, or porcine insulin in a dose-dependent manner, with lowest effective doses of 6.7, 96, and 53 mg/L, respectively. Time-course studies showed that hCG secretion peaked at 72-96 h with insulin exposure; in contrast, no decernable peak was seen without insulin in serum-free media. Exposure of JEG-3 cells for 24 h to 209 mg/liter insulin stimulated hCG synthesis, with 40 +/- 3% more immunoreactive intracellular hCG (P less than 0.05). Cells grown in the presence of insulin and [35S]methionine had 47 +/- 21% more labeled intracellular hCG and 56 +/- 13% more immunoprecipitable [35S]methionine-hCG secreted into the medium than the control cultures (P less than 0.05). During this time period, human placental lactogen release and total trichloroacetice acid-precipitable [35S]methionine protein were not increased. The insulin-induced stimulation of hCG synthesis was inhibited by cycloheximide. Additionally, insulin did not significantly affect total intracellular protein during 24-96 h of incubation. Insulin also increased hCG release from JAR cells, but not from human term trophoblast cells. A mouse monoclonal antibody to the IGF-I receptor inhibited the stimulation of insulin in JEG-3 cells. We conclude that insulin stimulates the synthesis and secretion of hCG from JEG-3 cells and JAR cells, and that hCG regulation in choriocarcinoma cells differs from that in primary human placental trophoblast cells. The effect of insulin on JEG-3 cells may be mediated in part through the insulin-like growth factor-I receptor.

Animals↗
PubMed1991

Octreotide stimulates insulin-like growth factor binding protein-1 (IGFBP-1) levels in acromegaly.

Insulin-like growth factors (IGFs) circulate in a complexed state with several binding proteins (BPs). Of these, IGFBP-1 is regulated by hormonal and nutritional factors. The somatostatin analogue, octreotide, has been used to effectively control hypersomaototropism in acromegaly. IGFBP-1 levels were measured by RIA in 17 acromegalic patients receiving octreotide. Serum hormone sampling was conducted hourly for 8 hr periods. Among 13 octreotide responders, mean pre-treatment basal GH, IGF-1, and IGFBP-1 levels were 19 +/- 5 micrograms/L, 1021 +/- 168 micrograms/L, and 36 +/- 8 micrograms/L respectively. One month following octreotide treatment, an acute subcutaneous injection (100 micrograms) maximally attenuated GH to 3 +/- 0.6 microgram/L (18% of control, P less than 0.03) and IGF-1 to 467 +/- 75 micrograms/L (46% of control, P less than 0.008) after 4 hrs. IGFBP-1 levels, however, were stimulated to 95 +/- 16 micrograms/L (297% of control, P less than 0.003) during the same time period. A significant increase in IGFBP-1 levels occurred within 2 hrs (158% of baseline, P less than 0.03), and was sustained until the 7th hr following injection. Insulin, a known suppressor of IGFBP-1, did not change during this time. Among the 4 octreotide non-responders, mean basal IGFBP-1 levels were 42 +/- 4 micrograms/L, and 4 hrs following octreotide administration IGFBP-1 was 40 +/- 7 micrograms/L. Octreotide induced a dynamic inverse relationship between circulating GH and IGFBP-1 levels (r = -0.73, P less than 0.001). The absence of IGFBP-1 changes in octreotide non-responders and the non-suppression of insulin in octreotide responsive patients, suggest a direct GH-mediated mechanism of IGFBP-1 regulation in octreotide treated patients with acromegaly. IGFBP-1 may be another useful marker in evaluating the response of acromegaly to octreotide treatment in patients who experience clinical benefit but equivocal GH and IGF-1 attenuation.

Acromegaly↗
PubMed1991

Gonadotropin secretory abnormalities.

Normal physiology of puberty and normal GnRH, LH, FSH, and hCG secretion have been reviewed. Systemic disorders can affect the neuroendocrine axis and cause varying degrees of hypogonadism by acting at different levels in the axis. As both hypothalamic abnormalities and intrinsic pituitary abnormalities can cause an abnormal FSH/LH response to GnRH, this test does not distinguish hypothalamic from pituitary mechanisms of hypogonadism. Therefore, only in disorders that have been demonstrated to have a structural pituitary abnormality (e.g., iron or granulomatous infiltration of the gonadotrophs) can we be certain that the disorder has its effect at the level of the pituitary. Abnormalities leading to hypersecretion (both ectopic and eutopic) of gonadotropins have also been described. To date, ectopic production of FSH and LH has not been unequivocally demonstrated. Systemic disorders cause mainly hypogonadism, many of the symptoms of which are reversible with control or cure of the disease. The effect of hypersecretion of gonadotropins on the reproductive system depends on the age at which the tumor (ectopic/eutopic) occurs.

Adenoma↗
PubMed1990

Expression of alpha- and beta-human chorionic gonadotropin subunits in cultured human cells.

We surveyed several human cell lines for production of alpha- and beta-human chorionic gonadotropin (hCG) under a variety of conditions known to induce gene expression. alpha- and beta-hCG subunits were monitored in culture media by specific radioimmunoassays and were shown to be quite sensitive to serum refeeding and growth state of all cell types studied. The permanent line JEG-3 secreted both alpha- and beta-subunits whereas HeLa cells secreted only the alpha-subunit. Production of both subunits was augmented in these permanent cell lines, for each growth state, by pretreating cells with 5-azacytidine; in contrast, spontaneous beta-hCG production by normal human fibroblasts (four of six strains) was only rarely increased after 5-azacytidine treatment, and more often was suppressed by 30 to 40%. Three of five strains from inherited chromosomal breakage syndromes produced immunoassayable beta-hCG spontaneously, two of which increased secretion upon treatment with either UV or mitomycin C. Surprisingly, one normal cell strain of fetal origin was induced to secrete alpha-hCG, but not beta-hCG, after UV irradiation. JEG-3 and HeLa cells produced detectable cognate mRNA for alpha- or beta-hCG subunits or both by Northern and S1 nuclease protection analyses, whereas such transcripts from untransformed human fibroblasts were consistently below detectable levels. Quantitation of beta-hCG mRNA by RNA:RNA annealing kinetics indicates that even the fibroblast strain producing the highest secreted beta-hCG levels contained cognate mRNAs at only approximately 0.1 per cell. We conclude that hCG expression in human fibroblasts is strongly repressed at the transcriptional level, although a variety of conditions (growth state, serum refeeding, cell senescence, or DNA damage) can affect the level of "leaky" expression, at least in some responding fraction of cells.

Cell Division↗
PubMed1990

Purified first and third trimester placental trophoblasts differ in in vitro hormone secretion.

In vitro studies with cytotrophoblasts obtained from term placentas have shown low levels of placental protein hormone secretion during the first 2 days in culture, followed by a marked increase during days 3 and 4. Since maternal serum placental hormone levels at term and during the first trimester differ, it is conceivable that cytotrophoblasts from first trimester placentas will differ in endocrine function from those derived from term placentas. Therefore, we examined the secretion of hCG, hCG alpha, human placental lactogen (hPL), and progesterone (P) both in the basal state and after exposure to 8-bromo-cAMP or endogenous cAMP stimulation with cholera toxin in cytotrophoblasts purified by enzymatic dispersion and Percoll gradient centrifugation from four first trimester and four third trimester placentas. At the time of seeding, all cells were mononuclear, and the degrees of aggregation and syncytia formation were similar in first and third trimester trophoblasts during the 4 days in culture. First trimester trophoblasts secreted greater quantities of hCG than did term trophoblasts, while basal secretion of hCG alpha, hPL, and progesterone were similar. Qualitative differences in the hormone secretory patterns were apparent. hCG secretion by first trimester trophoblasts decreased over the 4 days in culture, while the amounts secreted by third trimester trophoblasts increased. hCG alpha levels increased for 2-3 days in first trimester trophoblasts and then decreased, while hCG alpha increased in term trophoblast medium over the 4 days. The ratio of hCG alpha to hCG in media from first and third trimester cultures reflected the relative ratios of these hormones in placental tissue and maternal serum at analogous stages of pregnancy. hPL concentrations in the medium declined between days 3-4 in first trimester cultures, while they increased between days 3-4 in third trimester cultures. The secretory pattern of P was somewhat more erratic. cAMP stimulation led to a similar rise in hCG, hCG alpha, and P secretion in first and third trimester trophoblasts, and a variable response for hPL secretion. These results indicate that the functional activity of placental trophoblasts in culture depends in part upon the age of the placenta from which the cells are derived. The differences may represent intrinsic differences in function or the presence of inhibitory or stimulatory factors of maternal, fetal, or trophoblast origin.

Adult↗
PubMed1990

Progesterone and human chorionic gonadotropin do not stimulate placental proteins 12 and 14 or prolactin production by human decidual tissue in vitro.

To investigate the regulation of the synthesis and secretion of placental proteins-12 (PP12) and -14 (PP14) and PRL, explants and enriched preparations of stromal cells and gland cells obtained from 10 human early pregnancy decidua were preincubated in medium for 24 h (baseline), followed by incubation in medium with or without progesterone (0.02-32 mumol/L), hCG (10 and 100 ng/ml), or cAMP (0.25-1 mmol/L) in an atmosphere of 5% CO2-95% air at 37 C for another 96-120 h. Media were changed each 24 h, and PP12, PP14, and PRL levels were determined by RIA. Decidual explants, as well as their isolated cells produced detectable levels of PP12, PP14, and PRL in vitro. The gland cells synthesized and secreted about 30 times more PP14 than did stromal cells. After 96-120 h of incubation, the production of each protein by control cultures was increased 81-167% compared to the baseline (not significant). The secretion of these proteins in medium supplemented with progesterone or hCG was not significantly different from that in the control groups. 8-Bromo-cAMP significantly increased the secretion of PRL and PP12, but not PP14, by stromal cells compared to control values. We conclude that 1) PP14 is mainly produced by decidual gland cells; 2) progesterone at the concentrations used in our study does not stimulate production of PP12, PP14, and PRL in decidualized endometrium in vitro; 3) hCG does not stimulate the production of PP12 and PP14 in decidualized endometrium; and 4) 8-bromo-cAMP stimulates decidual stromal cell secretion of PRL and PP12.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Serum concentrations of two endometrial proteins are not useful for monitoring postmenopausal estrogen/progesterone therapy.

Measurements of the serum concentrations of the endometrial proteins IGFBP-1 and PP14 were made in an attempt to monitor the adequacy of the P effect in women receiving 1 year of 100 to 200 micrograms of percutaneous E2 for 28 days each month and 10 mg oral MPA given during the last 12 days of E2 administration. There were no significant changes in IGFBP-1 levels; a small, but significant increase in PP14 levels after E2 plus MPA was noted, but there was substantial overlap between basal and postprogestogen therapy serum PP14 concentrations. Serum concentrations of PP14, but not IGFBP-1, were slightly higher in women whose endometrial biopsies demonstrated a P effect, but again, there was substantial overlap with the values found in women whose biopsies showed only an estrogen effect. Serum measurements of IGFBP-1 and PP14 are not useful for monitoring postmenopausal replacement therapy with percutaneous E2 and oral MPA.

Adult↗
PubMed1990

Placental proteins as tumor markers.

Among the three placental proteins discussed, HCG is the only clinically useful tumor marker, and the value of HCG measurements is restricted to patients with gestational and nongestational trophoblastic disease. In patients with gestational trophoblastic disease, HCG levels may serve as an adjunct for the diagnosis, provide prognostic information, and be an objective parameter to evaluate the effects of therapy. Little or no additional information is obtained from HPL or SP-1 measurements. In patients with germ cell neoplasms of the testis, HCG measurements add useful information for clinical staging and monitoring of therapy, although discordance between tumor growth and HCG levels can be found in patients whose tumors contain several different elements. Therefore, AFP measurements must be made as well in these patients to monitor disease activity. Neither HPL nor SP-1 measurements are useful in these patients. None of the placental proteins are useful for screening, as prognostic indicators, or for evaluating the effects of therapy in groups of patients with nontrophoblastic neoplasms. In some patients with nontrophoblastic malignancies, each of the markers may accurately reflect changes in tumor burden during therapy. However, the problems with specificity and sensitivity of the tests and the fact that the majority of patients whose tumors produce the hormone have circulating concentrations that are at the limits of detection of the assays decrease the utility of these measurements and render them cost-ineffective for routine patient care.

Biomarkers, Tumor↗
PubMed1989

Photodynamic therapy of human choriocarcinoma transplanted to the hamster cheek pouch. II. Intra-lesional photosensitization.

Photodynamic therapy (PDT) uses light-activated compounds, such as hematoporphyrins, to produce cytotoxic effects after illumination. Human choriocarcinoma cells were transplanted into the hamster cheek pouch to study PDT. The transplanted choriocarcinoma secretes human chorionic gonadotropin (hCG) in proportion to tumor volume. Red light (630 nm) from an argon-pumped dye laser (100-200 J/cm2) was used to illuminate tumors sensitized with dihematoporphyrin ether (DHE). Previous work has demonstrated complete regression (CR) of 90% of tumors (18/20) after one or two PDT sessions, while contralateral cheek pouch tumors continued to grow despite intraperitoneal DHE. Neither DHE nor laser light alone resulted in significant CRs. In this study we evaluated intratumoral injection of DHE followed in 2 hr by laser treatment. In all tumors, localization of DHE was demonstrated by induced fluorescence with ultraviolet light or He:Cd laser. After a single treatment, 14 of 38 tumors (37%) completely regressed (hCG less than mIU/ml); 4 tumors regressed grossly with low-level hCG [partial regression (PR)]. After repeat treatment there were 10 additional CRs in 19 rapidly enlarging tumors. After a third treatment 3 CRs and 3 PRs were achieved in 6 tumors. Because of large volumes, 2 of 3 progressing tumors failed to fluoresce uniformly after intratumoral DHE and were treated after intraperitoneal DHE injection; both completely responded. Overall, 29 of 38 tumors (76%) completely responded to PDT, and 7 partially responded (18%) with no gross tumor remaining in 5 of the 7. Only 5% of tumors (2/38) were non-responders. Photodynamic therapy results in gross elimination of 90% of tumors (52/58) in this model after intraperitoneal or intratumoral DHE sensitization (P less than 0.0001). DHE in chorio-carcinomas is easily detected and may enable detection of occult foci of malignancy. Choriocarcinoma transplanted into the hamster cheek pouch is highly responsive to photodynamic therapy. Clinical trials of PDT in gynecologic cancers are warranted to confirm the high response rates observed in refractory nongynecologic cancers.

Animals↗
PubMed1989

Comparison of serum placental protein hormone levels in diabetic and normal pregnancy.

Conflicting data exist concerning maternal serum concentrations of placental hormones during pregnancy in women with diabetes mellitus. To resolve some of these discrepancies, women participating in the NICHD-Diabetes in Early Pregnancy Study were studied. In this collaborative study, pregnancy was identified within 21 days of conception by serum hCG measurements. We prospectively collected 185 blood samples from 35 insulin-dependent diabetic women and 166 blood samples from 31 control women, all between 5 and 37 weeks gestation. Serum concentrations of hCG, pregnancy-specific beta-1-glycoprotein, placental lactogen, and hCG alpha were measured serially. The relationship between serum hormone, fasting blood glucose, 1-h postprandial blood glucose, and glycosylated hemoglobin concentrations was compared. Serum hCG alpha levels were significantly lower in the diabetic women than in control women at multiple time points during the first and second trimesters, while no consistent differences in the serum concentrations of hCG or pregnancy-specific beta-1-glycoprotein were found between pregnant diabetic and control women. Serum placental lactogen levels were significantly lower in diabetic women at 9-10 weeks and 20 weeks gestation. There were no correlations between fasting blood glucose, 1-h postprandial blood glucose, or glycosylated hemoglobin and any of the placental protein levels in the diabetic women. These data are consistent with a defect in synthesis and/or secretion of hCG alpha by the cytotrophoblast during the first two trimesters of pregnancy in insulin-requiring diabetic women.

Adult↗