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S Handwerger

Publications and source records attributed to S Handwerger.

At least 127 records · Page 7Linked to original sources
PubMed1985

Somatomedin-C stimulates glycogen synthesis in fetal rat hepatocytes.

The effects of somatomedin-C/insulin-like growth factor I (Sm-C) on glycogen metabolism in cultured hepatocytes from 20-day-old rat fetuses have been examined and compared with the effects of insulin. Sm-C (25-375 ng/ml; 3.25-50 nM) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen (14.4-72.9%; P less than 0.001) and total cell glycogen content (10.6-34.3%; P less than 0.01). Maximal stimulation of glycogen synthesis by Sm-C occurred at 2-4 h of incubation. Insulin (10 nM to 10 microM) also stimulated [14C]glucose incorporation but its potency was only 1/20th that of Sm-C. The time course of stimulation of glucose incorporation by insulin was identical to that of Sm-C, the dose-response curves of the two hormones were parallel, and the maximal effects of insulin were not enhanced by simultaneous exposure of cells to Sm-C. These findings suggest that Sm-C and insulin stimulate glycogenesis in fetal liver through similar or identical mechanisms. Since the potency of Sm-C was 20 times greater than that of insulin, the glycogenic action of insulin in fetal liver may be mediated through binding to a hepatic receptor which also binds Sm-C. In addition to having mitogenic effects on fetal tissues, Sm-C may have direct anabolic effects on fetal carbohydrate metabolism.

Animals↗
PubMed1985

Differences in the cell surface antigens of prolactin-producing cells of human decidual and pituitary tissues.

Anterior pituitary cells and other endocrine cells which synthesize and release protein hormones share the cell surface ganglioside antigens A2B5 and 3G5. In addition, these peptide hormone-producing cells contain chromogranin, a major protein component of secretory vesicles. Since human decidual cells synthesize and release a PRL that has chemical and biological properties indistinguishable from those of pituitary PRL, we examined by immunochemical techniques whether decidual cells also contain cell surface antigens A2B5, 3G5, and chromogranin. In these studies, human decidual tissue from three pregnancies and human and rat pituitary tissues were processed and stained with mouse monoclonal antibodies to A2B5, 3G5, and chromogranin by indirect immunofluorescence using fluorescein-conjugated sheep antimouse gamma-globulin. In all instances, the pituitary and pancreatic tissue stained strongly with the monoclonal antibodies to the cell surface antigens, but the decidual tissues from the three pregnancies did not. The pituitary and pancreatic cells also stained strongly with the monoclonal antibody (LK 2H10) to chromogranin, but the decidual tissues had no reactivity. In control experiments, the decidual tissues stained strongly with a monoclonal antibody to HLA antigens, and none of the tissues stained with nonimmune gamma-globulin. These results strongly suggest that the PRL-producing cells of human decidua and pituitary have different cell surface antigens. The observation that decidual cells do not contain chromogranin is consistent with previous biochemical studies suggesting that decidual PRL is not stored in secretory granules. The differences in the subcellular localization of PRL in decidual and pituitary tissues may explain, in part, the differences in the regulation of PRL release from these tissues.

Animals↗
PubMed1985

Stimulation of ovine placental lactogen secretion by arachidonic acid.

To determine whether arachidonic acid stimulates the secretion of ovine placental lactogen (oPL), arachidonic acid was infused as an intravenous bolus into pregnant ewes and fetuses. Plasma oPL concentrations were determined in mothers and fetuses before and for 5 h after infusion. The administration of 12.5 mg arachidonic acid (0.15-0.2 mg/kg, n = 11 experiments) to the pregnant ewes caused an increase in maternal plasma oPL concentrations of 73.9 +/- 15.6% (S.E.M.) and 60.8 +/- 18.1% above the pretreatment concentrations at 4 and 5 h respectively (P less than 0.01 in each instance). The infusion of 25 mg arachidonic acid (n = 8) caused increases of 96.0 +/- 19.1% and 100.3 +/- 26.4% (P less than 0.005), and the stimulation was not inhibited by the cyclo-oxygenase inhibitors indomethacin and ibuprofen. In contrast to arachidonic acid, vehicle alone or palmitic acid had no effects on plasma oPL concentrations. Despite the increase in maternal plasma oPL concentrations, plasma oPL concentrations in the fetus remained unchanged after the maternal infusions. The infusion of arachidonic acid (0.5-1.5 mg/kg) directly into six fetuses had no effects on either fetal or maternal oPL concentrations. These studies indicate that arachidonic acid stimulates maternal plasma oPL concentrations but has no effect on fetal oPL concentrations and the stimulation of oPL secretion is not due to the conversion of arachidonic acid to prostaglandins or other cyclo-oxygenase products.

Animals↗
PubMed1985

Arachidonic acid stimulates phosphoinositide hydrolysis and human placental lactogen release in an enriched fraction of placental cells.

Previous investigations in this laboratory have indicated that arachidonic acid stimulates a rapid, dose-dependent, and reversible increase in human placental lactogen (hPL) release which is not dependent on cyclooxygenase or lipoxygenase metabolism. To investigate further the mechanism by which arachidonic acid stimulates the release of hPL, the effects of arachidonic acid on phosphoinositide hydrolysis were examined in an enriched cell culture population of term human syncytiotrophoblast. Phosphoinositide hydrolysis was assayed by three methods: the release of 3H from perfused cells prelabeled with [3H]myoinositol, the measurement of inositol phosphate accumulation, and the distribution of radioactivity in phospholipids separated by two-dimensional thin layer chromatography after exposure of 32P-labeled placental cells to arachidonic acid. Arachidonic acid stimulated a concentration-dependent, rapid, and reversible increase in the release of both [3H]myoinositol and hPL from perfused placental cells. This effect was not inhibited by prior incubation of cells with indomethacin (20 microM). In contrast, palmitic acid and oleic acid stimulated phosphoinositide hydrolysis only at a high concentration (100 microM). Arachidonic acid also stimulated the rapid appearance of inositol monophosphate in placental cells. The effect of arachidonic acid was specific for hydrolysis of phosphoinositides and phosphatidylserine and did not involve other phospholipids. Since phosphoinositide hydrolysis is associated with hormone release in a variety of secretory systems, these results suggest that the stimulation of hPL release by arachidonic acid may be mediated, at least in part, by the activation of phospholipase C.

Arachidonic Acid↗
PubMed1984

Glycogenolytic effects of the calcium ionophore A23187, but not of vasopressin or angiotensin, in foetal-rat hepatocytes.

Vasopressin, angiotensin and phenylephrine stimulate glycogenolysis in postnatal rat liver by a Ca2+-mediated mechanism not involving cyclic AMP. To determine whether these hormones promote glycogenolysis in foetal liver, we have examined their effects, and those of the Ca2+ ionophore A23187, on glycogen metabolism in cultured foetal-rat hepatocytes. Vasopressin and angiotensin (0.1 nM-0.1 microM) had no effects on either glycogen synthesis (as assessed by [14C]glucose incorporation into glycogen) or phosphorylase a activity. However, A23187 at 1 and 10 microM inhibited glycogen synthesis by 31.3 and 89.1% respectively (both P less than 0.001) and stimulated phosphorylase a activity by 66.9 and 184.1% respectively (both P less than 0.01). Incubation of cells in Ca2+-deficient medium attenuated the effects of 10 microM-A23187 on glycogen synthesis and abolished the effects of 1 microM-A23187. As in postnatal liver, glucagon (1 and 20 nM) and isoprenaline (1 and 10 microM), which activate adenylate cyclase, inhibited glycogen synthesis and stimulated phosphorylase a activity in foetal hepatocytes. The minimal effective concentration of phenylephrine was 10 times that of isoprenaline. These results indicate striking differences in the ontogeny of cyclic AMP-mediated and Ca2+-mediated processes which regulate hepatic glycogenolysis. Since increases in cytosolic Ca2+ induce glycogenolysis in foetal-rat liver, the weak or absent responses to vasopressin, angiotensin and the alpha-adrenergic agonists may result from defects in hormone-receptor binding or in post-receptor events leading to the mobilization of intracellular Ca2+ stores.

Angiotensin II↗
PubMed1984

Different subcellular storage sites for decidual- and pituitary-derived prolactin: possible explanation for differences in regulation.

The intracellular sites of storage for human decidual- and pituitary-derived prolactins have been determined by measuring the hormones in subcellular fractions following differential and density gradient centrifugations. In decidual tissue, 78 +/- 4% (mean +/- SE, n = 5) of the prolactin was detected in the post-microsomal supernatant, while 98% of the prolactin in the pituitary was detected in mitochondrial and microsomal particulate fractions. Following centrifugation on sucrose density gradients, decidual prolactin was distributed diffusely throughout the gradients, while greater than 90% of the pituitary prolactin sedimented as a single peak with a mean density of 1.22 g/cm3. These studies indicate that, unlike pituitary prolactin, decidual prolactin is not stored in secretory granules. Differences in the intracellular storage sites of decidual and pituitary prolactins may explain observed differences in the regulation of prolactin secretion by decidual and pituitary tissues.

Animals↗
PubMed1984

Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes.

The effects of placental lactogen on glycogen metabolism have been studied in cultured hepatocytes from 20-day-old fetal rats. Ovine placental lactogen (oPL; 2, 5, 10, and 25 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen and total cellular glycogen content after 4 h of incubation but had no effect on glycogen degradation. Half-maximal stimulation occurred with an oPL concentration of 3 micrograms/ml. In contrast, human placental lactogen had no effect on [14C]glucose incorporation into glycogen. Ovine growth hormone (50 and 100 micrograms/ml), rat growth hormone (20, 40, and 100 micrograms/ml), and ovine prolactin (10, 40, and 100 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen, but the potencies of these hormones were only 10-20% of that of oPL. Insulin (20 nM) stimulated [14C]glucose incorporation into glycogen, whereas glucagon (0.5 and 20 nM) inhibited [14C]glucose incorporation into glycogen and increased glycogen degradation. Our findings suggest that oPL may have direct insulin-like effects on carbohydrate metabolism in the fetus and that oPL may contribute to the accumulation of fetal liver glycogen that occurs in late gestation.

Animals↗
PubMed1984

Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes.

The interactions between ovine placental lactogen (oPL) and insulin in the regulation of fetal liver glycogen metabolism have been studied in cultured hepatocytes from fetal rats on day 20 of gestation. Both oPL (0.75-22.5 micrograms/ml) and insulin (0.01-1 microM) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen. However, the dose-response curves for the two hormones were not parallel and the maximum effect of oPL was 3.4 times greater than that of insulin (P less than 0.001). The two hormones had synergistic effects on [14C]glucose incorporation at low concentrations and additive effects at maximum concentrations. Ovine growth hormone (oGH) also stimulated [14C]glucose incorporation into glycogen but with a potency only 12.3% that of oPL. Cycloheximide (20 microM) abolished the stimulation of [14C]glucose incorporation by insulin (1 microM), oPL (5 micrograms/ml), and oGH (100 micrograms/ml). Although the glycogenic actions of oPL and insulin may depend on new protein synthesis, the results of these studies suggest that these hormones stimulate glycogen synthesis in fetal liver by different mechanisms. Because the glycogenic actions of oPL are potentiated by insulin, these hormones may act in concert to promote hepatic glycogen storage in the fetus.

Animals↗
PubMed1984

Peritoneal fluid prolactin in infertile women with endometriosis: lack of evidence of secretory activity by endometrial implants.

To evaluate the functional status of endometriotic implants, a luteal secretory product of endometrium, PRL, was measured in the PF of 27 infertile women with endometriosis, 13 infertile women without endometriosis, and 11 fertile women undergoing elective sterilization. PF PRL concentrations and PF/plasma PRL ratios were similar in all the groups and did not vary with the menstrual cycle or the stage of endometriosis. These data demonstrate that the ectopic endometrium in infertile women with endometriosis does not secrete PRL in amounts sufficient to elevate PF concentrations and suggest that the infertility observed in these women is probably not dependent upon the secretory activity of endometriotic implants.

Adult↗
PubMed1983

Ovine placental lactogen, but not growth hormone, stimulates amino acid transport in fetal rat diaphragm.

Previous studies from this laboratory indicate that ovine placental lactogen (oPL) and ovine growth hormone (oGH) stimulate amino acid transport in diaphragms of postnatal rats with equal potencies. However, in studies reported here using diaphragms from fetal rats on day 20 of gestation, oPL (2,5 and 20 micrograms/ml) stimulated a dose-dependent increase in amino acid uptake, while oGH (5,20 and 100 micrograms/ml) and rat growth hormone (rGH, 2 and 40 micrograms/ml) were without effect. The effect of oPL on fetal AIB transport was neither enhanced nor antagonized by oGH (100 microgram/ml). The magnitude of stimulation of AIB transport by oPL was comparable to that observed with insulin (100 and 1000 microU/ml). Human placental lactogen (hPL) and ovine prolactin (oPRL) had no effect on fetal AIB transport. Since oPL is present in high concentrations in fetal blood, these studies suggest that oPL may have a direct role in the regulation of fetal amino acid and protein metabolism, that oPL and oGH may bind to different receptors in fetal rat tissues, and that oPL may function as a "fetal growth hormone".

Amino Acids↗
PubMed1983

Characterization of the synthesis and release of prolactin by an enriched fraction of human decidual cells.

An enriched fraction of human decidual cells that synthesizes and releases human PRL (hPRL) was obtained by isopycnic centrifugation of collagenase- and hyaluronidase-dispersed cells through Percoll. The cells that synthesized and released hPRL banded at a density of 1.017-1.045 g/ml, an area of the gradient comprising only a small percentage of the total decidual DNA. The enriched cells formed distinct colonies in culture and contained hPRL, as evidenced by indirect immunofluorescent staining with anti-PRL serum. Plated at a density of 5.0 x 10(5) cells/well, the cells produced hPRL at a mean rate of 8.1 +/- 1.1 ng/microgram DNA . 24 h (mean +/- SD) for 8 days. Like decidual explants, the enriched cells responded to phospholipase A2 (0.1 U/ml) with a 54% decrease in hPRL release and to placental conditioned medium (0.5 mg protein/ml medium) with a 62% increase. Insulin (8.3 x 10(-7) M), progesterone (10(-5) - 10(-12) M), and estradiol (10(-5) - 10(-12) M) did not affect hPRL release over 6 days. These results indicate that enriched PRL-releasing cells, obtained by the isopycnic centrifugation of collagenase- and hyaluronidase-dispersed cells, are a useful model for the study of the synthesis and release of PRL.

Cell Separation↗
PubMed1983

Characterization of the synthesis and release of human placental lactogen and human chorionic gonadotropin by an enriched population of dispersed placental cells.

An enriched fraction of human placental cells that synthesize and release both placental lactogen (hPL) and hCG was obtained by isopycnic centrifugation of collagenase/hyaluronidase-dispersed cells through a density gradient of 40% Percoll. The enriched cells, which banded at a density of approximately 1.01 g/ml, comprised 10-15% of the total DNA. During the first 24 h after attachment, the cells released 50-250 ng hPL and 4-10 mIU hCG/10(6) cells. Thereafter, the rate of hPL release decreased, while the rate of hCG and [35S]trichloroacetic acid-precipitable protein release remained constant. The enriched cells responded to phospholipase A2, low extracellular calcium, and (Bu)2cAMP in a manner similar to that of placental explants. Phospholipase A2 (0.1 and 1 U/ml) stimulated hPL release by 270% and 568%, respectively, and low extracellular calcium (0-0.18 mM) stimulated hPL release by 48%. (Bu)2 cAMP (1 mM) stimulated hCG release by 42%, but had no effect on hPL. Estradiol (10(-5)-10(-12) M) and progesterone (10(-5)-10(-10) M) had no effect on the synthesis and release of either hPL or hCG over a 6-day period. In addition, insulin (8.3 X 10(-7) M) and changes in medium glucose content (0-5 mg/ml) had no effect on hPL release over a 72-h period. Since the enriched trophoblast cells respond to provocative stimuli in a manner similar to that of explants and placental fragments, this cell population is a useful model system for investigations of the cellular mechanisms of hPL and hCG release.

Bucladesine↗
PubMed1983

Inhibition of decidual prolactin release by a decidual peptide.

Conditioned media from cultures of human decidual explants and aqueous extracts of human decidual tissue contain a factor that causes a reversible dose-dependent inhibition of decidual PRL release in vitro. Decidual explants incubated for 30 min in medium containing 50, 100, and 250 micrograms/ml of a dialyzed and lyophilized preparation of decidual conditioned medium (DCM) released 32.4 +/- 2.7%, 70.9 +/- 4.5%, and 100.0%, respectively, less PRL than control explants. DCM, however, had no measurable effect on the synthesis of decidual PRL or the synthesis and release of trichloroacetic acid-precipitable 35S-labeled proteins. The effect was of short duration and completely reversible. The inhibition of decidual PRL release was not due to PRL, since 500 micrograms/ml human pituitary PRL (a PRL concentration 40 times that in the minimal effective dose of DCM) added to the incubation medium of decidual explants had no effect on the synthesis or release of decidual PRL or trichloroacetic acid-precipitable 35S-labeled decidual proteins. The inhibitory activity eluted from Sephadex G-200 with an apparent molecular weight of 38,000-45,000 daltons, was heat labile, was destroyed by treatment with trypsin, and was unaffected by extraction with acetone-ethanol. These results strongly suggest that the release of decidual PRL is under local control, regulated in part by a factor(s) other than PRL that is released by the decidua.

Animals↗
PubMed1983

Serum somatomedin C concentrations in the fetal sheep increase markedly during gestation.

Serum somatomedin C concentrations in fetal sheep and pregnant ewes from days 51 to 149 of gestation were determined by specific radioimmunoassay. In the fetus (n = 61 samples) serum somatomedin C concentrations, fitted to a regression curve, increased significantly with advancing gestation from 0.44 units/ml at 51 days to 3.99 units/ml at 149 days, an increase of 806% (P less than 0.001). In the pregnant ewes (n = 14 samples), serum somatomedin C did not change during gestation. The temporal relationship between the marked increase in fetal somatomedin C concentrations and the acceleration of fetal growth is consistent with the hypothesis that somatomedin is important in the stimulation of fetal growth.

Animals↗
PubMed1983

Differential effects of ornithine on placental lactogen and growth hormone secretion in the pregnant ewe and fetus.

The intravenous infusion of ornithine (0.5-0.9 g/kg) into five fetal sheep of 116-141 days gestation caused no significant change in concentrations of fetal plasma placental lactogen (PL) or GH as determined by specific homologous radioimmunoassays. In contrast, the intravenous infusion of ornithine (0.3-0.5 g/kg) into three of the ewes caused a 144.5 +/- 74.7 (S.E.M.)% increase in maternal plasma PL concentrations and a 255.2 +/- 55.0% increase in maternal GH concentrations. Fetal PL concentrations remained unchanged depsite the large increase in maternal PL concentrations. This study, which indicates a differential effect of ornithine on PL and GH secretion in the mother and fetus, suggests that the factors regulating PL and GH secretion in the mother and fetus are distinct.

Animals↗
PubMed1983

Failure of acute changes in prolactin to affect DHEA-S secretion in the human.

To investigate whether acute changes in prolactin secretion affect adrenal androgen secretion, serum prolactin and dehydroepiandrosterone sulfate (DHEA-S) concentrations were determined in seven normal women following the administration of chlorpromazine and L-dopa. The changes in plasma prolactin and DHEA-S concentrations over a four-hour period were compared to those in control experiments in which four of the women received placebo alone. Following the administration of chlorpromazine, plasma prolactin concentrations increased four-fold above pretreatment concentrations, reaching a maximum at 120 minutes. Following L-dopa, plasma prolactin concentrations decreased by greater than 50%, with the nadir noted within 90 minutes. Despite these acute changes in prolactin secretion, plasma DHEA-S concentrations remained unchanged. These results, therefore, strongly suggest that acute changes in prolactin secretion have no affect on adrenal androgen secretion.

Adult↗