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C Polychronakos

Publications and source records attributed to C Polychronakos.

65 records · Page 4Linked to original sources
PubMed1985

Increase in the type 2 insulin-like growth factor receptors in the rat kidney during compensatory growth.

We have observed an increase in binding of IGF-I and IGF-II to microsomes obtained from rat kidneys undergoing compensatory growth following contralateral nephrectomy. This increase was evident by the 4th day and it preceded observable growth of the kidney. Binding returned to control levels just prior to the flattening of the growth curve of the kidney. The increase was due to an increase in the type 2 binding sites, the only type unequivocally present, from 95.3 +/- 2.7 to 117.2 +/- 4.1 pM/150 micrograms of microsome protein at its maximum at 4 days.

Animals↗
PubMed1985

Acute reversal of the enhanced insulin action in trained athletes. Association with insulin receptor changes.

We studied the effect of aerobic training and detraining on insulin-stimulated glucose disposal and on erythrocyte insulin receptor binding. Seven endurance-trained athletes were studied at 12 h, 60 h, and 7 days after cessation of training and compared with three untrained, age- and weight-matched controls. The metabolic clearance rate of glucose as measured by the euglycemic clamp technique was 15.6 +/- 1.8 ml/kg/min (mean +/- SEM) in the trained subjects 12 h after the last bout of exercise compared with 7.8 +/- 1.2 ml/kg/min in the untrained control group. When the trained subjects refrained from physical training, the metabolic clearance rate decreased to 10.1 +/- 1.0 ml/kg/min at 60 h and further to 8.5 +/- 0.5 ml/kg/min after 7 days of detraining. The percentage of specific insulin binding to young erythrocytes (density 1.089-1.092), isolated by density gradient centrifugation, decreased from 10.4 +/- 0.9 at 12 h after the last exercise to 8.1 +/- 0.7%/3 X 10(9) cells after 60 h of detraining (P less than 0.001). The decrease in insulin binding to erythrocytes was almost entirely accounted for by a decrease in the number of insulin receptors. We conclude that the increase in peripheral insulin action seen in trained athletes is rapidly reversed, possibly by a mechanism separate from other phenomena associated with chronic training. The parallel findings of decreased in vivo insulin action and decreased insulin binding in young erythrocytes suggest that modulation of in vivo insulin response by detraining may be at least partially mediated by changes in insulin receptor number.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Receptors for the insulin-like growth factors on human erythrocytes.

We have examined the presence and properties of specific receptors for the insulin-like growth factors (IGFs) on human erythrocytes (RBC). HPLC purified IGF-I and II peptides were used as ligands. RBCs were separated in density fractions representing cell groups of different ages. Binding to all cell fractions was found for both IGF tracers. Porcine insulin displaced this binding only partially, with a potency that was at least 10 times lower. IGF-II was equipotent with IGF-I in displacing [125I] IGF-I binding, but was somewhat more potent than IGF-I in displacing its homologous tracer. In the youngest cell fraction from 7 normal adults, the level of specific binding per 3 X 10(9) cells was 5.2 +/- 0.4% (mean +/- SE) and 6.3 +/- 0.5% of added radioactivity for IGF-I and IGF-II respectively. It declined rapidly as a function of cell age. Binding for unfractionated cell samples was 2.2 +/- 0.1% and 3.1 +/- 0.1% respectively. We conclude that: a) Specific receptors for the IGFs exist on human erythrocytes. b) Binding to these receptors is dependent on cell age. c) The binding in isolated young RBCs is of sufficient magnitude to permit their use for the clinical measurement of these receptors.

Adult↗
PubMed1982

The role of cell age in the difference in insulin binding between adult and cord erythrocytes.

Erythrocytes (RBCs) from cord blood are known to bind more insulin than those of adults. We have investigated the possibility that this difference is due to the younger cell age of the neonatal cells. Samples from 13 normal full term neonates and 12 adults were fractionated into 5 fractions of defined density by dextran gradient centrifugation. Fractions of comparable density, a variable known to correlate well with age, were then compared for insulin binding. Plasma insulin and glucose levels were the same in the two study groups. The density distribution curve was shifted to the left for the cord samples, indicating a younger cell age. The difference was most marked in the lightest fraction, which contained 4.66 + 0.46% (mean +/- SE) adult cells vs. 15.26 +/- 1.27% cord cells (P less than 0.01). Insulin binding was identical when fractions of equal density were compared in the two groups. The only exception was the lightest (youngest) fraction (density, less than 1.092), in which the cord cells displayed a considerably higher percentage of specific binding; (19.98 +/- 1.57 vs. 13.32 +/- 0.92 P less than 0.005). This difference was shown to be due to a high percentage of very light cells in cord samples, compared to adult samples, in this fraction which, unlike the others, did not have a lower limit of density. When a lower density cutoff was introduced (1.089 g/ml), the remaining cells of this fraction (density, 1.089-1.092) displayed quite similar percentages of specific binding (13.07 +/- 1.63 vs. 11.86 +/- 1.27). Cells below this density were virtually absent in the adult, comprising less than 0.3% of all adult cells compared to 7.2% of the cord cells. These results indicate that the difference in insulin binding between adult and cord cells is due to a younger RBC age distribution in cord blood. This difference is most marked in the youngest cell fractions. Age fractionation of RBCs by density gradient centrifugation appears to be a promising method of assessing RBC insulin receptors in situations in which substantial changes in cell age are seen.

Adult↗
PubMed1981

Perinatal activity of the hypothalamic-pituitary-gonadal axis in the lamb. III. LH, testosterone and prolactin secretory pattern in newborn lambs.

Crossbred male and female lambs from Suffolk rams and Dorset-Finnish ewes born in January and February were studied at 1, 3, 7, 21 and 28 days of age and female lambs at 14 days. Ultradian variations in plasma luteinizing hormone (LH), prolactin (PRL) and testosterone were studied at 30-min intervals during a 4-hour period. In female lambs LH secretory peaks were observed at 7 days of age the amplitude of LH peaks increasing 8-fold between 7 and 14 days and 2-fold between 21 and 28 days. The number of secretory peaks also increased with age. Ultradian variations in PRL were observed from 1 day of age, the amplitude of the PRL peaks increasing also with age. In male lambs, LH and testosterone peaks were observed at 3 days of age, the testosterone peak being preceded by or concomitant with LH peaks. The amplitude of LH peaks increased with age together with basal testosterone levels although the amplitude of testosterone peaks was unchanged. This study demonstrates pulsatile secretion of LH and PRL in lambs of both sexes and of testosterone in male lambs in the first week of postnatal life. In addition, since the ovine testis is responsive to endogenous gonadotropic stimulation at this period, it is suggested that the hypothalamic-pituitary-gonadal axis is already operative at this age. It can be concluded that the hypothalamic activity concerned with pulsatile LH and prolactin secretion is present very early in the lamb neonate.

Animals↗
PubMed1981

Perinatal activity of the hypothalamic-pituitary-gonadal axis in the lamb. IV. Testicular responsiveness to hCG from 1 through 28 days of life.

Previous studies in this laboratory have shown the existence of an early postnatal activation of the hypothalamic-pituitary-gonadal axis (HPGA) in the male lamb which was present at 2 and 4 weeks of age. In order to define more precisely the time sequence of HPGA activity, we have studied the in vivo and in vitro testicular responsiveness to human chorionic gonadotropin (hCG) of the immature lamb at 1, 3, 7, 14, 21 and 28 days of life. Plasma testosterone (T) increments (delta) after hCG were lower in 1-day-old animals than in other age groups. Testicular concentrations of T, dehydroepiandrosterone and 17-hydroxyprogesterone increased from 1 to 14 days. Testicular 17, 20 lyase activity rose significantly with age but was not influenced by hCG. hCG and dibutyryl cyclic AMP increased significantly the T production by enriched interstitial cell preparation at 1, 3, and 7 days, the greatest response being found at 7 days. hCG also increased significantly the T production at 14 days. These data suggest that the lamb testis has the capacity to respond to hCG in vivo and to various stimuli vitro from the 1st day of life and that the response reaches a plateau from 2 to 4 weeks after birth.

Androstenedione↗
PubMedDate not supplied

Proteinolytic activity against IGF-binding proteins involved in the paracrine interactions between prostate adenocarcinoma cells and osteoblasts.

PA-III rat prostate adenocarcinoma cells are capable of inducing osteoblastic reaction after inoculation onto rat skeleton. In this study PA-III cells and osteoblast-derived rat osteosarcoma cells (UMR 106 cells) were employed to characterize the cellular interactions in the PA-III cell-induced bone tumors, in vitro. Insulin-like growth factor-I (IGF-I) and conditioned media (CM) of UMR 106 cells stimlated tritiated-thymidine incorporation into the DNA of PA-III cells growing in serum-free media. This effect was inhibited by monoclonal anti-hIGF-I antibody. In addition PA-III cell CM contained proteinolytic activity for the IGF-binding proteins of UMR 106 cell CM (IGFBP-1 and -2). This proteinase activity hydrolyzed also benzyloxycarbonyl-lysine thiobenzyl ester (BLT) and its action on IGFBPs and BLT was inhibited by benzamidine and aprotinin. Proteinase activity of PA-III cell CM when bound covalently to tritiated-dilsopropylfluoro-phosphate (DFP) and then analyzed on SDS-PAGE gel electrophoresis, revealed the presence of radioactivity linked with a 35 kDa protein band. This proteinase was eluted in the void volume of the G-50 sephadex column and was retained on and eluted from p-benzamidine affinity column. The 35 kDa proteinase was retained on and was eluted from cartridges of the C18 silica by 80% acetonitrile over 0.1% trifuroacetic acid. This partially purified material hydrolyzed BLT substrate and IGFBPs of UMR 106 cell CM and its effect was inhibited by benzamidine and aprotinin. These data indicate that PA-III cell CM contains a 35 kDa proteinase capable of digesting the IGFBPs and thus increases the bioavailability of osteoblast-derived IGFs. This mechanism may participate in the pathophysiology of the PA-III cell-induced bone tumor and its subsequent osteoblastic reaction.

Adenocarcinoma↗
PubMedDate not supplied

Somatostatin analogue SMS 201-995 reduces serum IGF-I levels in patients with neoplasms potentially dependent on IGF-I.

Tumors of several organs have been shown to bear cell surface receptors for insulin-like growth factor I (IGF-I), and to exhibit dependence on this mitogen for optimum proliferation both in vivo and in vitro. To investigate the feasibility of a novel form of endocrine therapy that would exploit such dependence, we treated 8 patients with non-endocrine solid tumours with the somatostatin analogue SMS 201-995, in an effort to reduce growth hormone-stimulated IGF-I production. Significant decreases in basal and arginine-stimulated serum growth hormone and serum IGF-I were noted. This approach deserves evaluation as a potentially useful form of palliative endocrine therapy for certain cancers.

Adult↗
PubMedDate not supplied

Urokinase-type plasminogen activator: a paracrine factor regulating the bioavailability of IGFs in PA-III cell-induced osteoblastic metastases.

The transplantation of PA-III rat prostate cancer cells onto rat skeleton produces osteoblastic metastases. Therefore w e studied the paracrine interactions between the PA-III cells and osteoblast-derived osteosarcoma cells (UMR 106 cells). A serine protease secreted by PA-III cells hydrolyzed IGF-binding protein-1 and IGF-binding protein-2 (IGFBP-1 and IGFBP-2) detected in the cell culture media (CM) of OMR 106 cells by western ligand blotting. The serine protease of PA-III cell CM was purified using a benzamidine affinity column. This protease was a protein of 45-50 kDa on polyacrylamide gel electrophoresis under non-reducing conditions but generated two protein bands under reducing conditions; a) one of 33-35 kDa possessing protease activity and b) another of 20-25 kDa which was proteinolytically inactive. Sequence analysis identified the amino acid sequence of the a-chain (20-25 kDa band) and of the b-chain (33-35 kDa band) of rat urokinase-type plasminogen activator molecule. Urokinase purified from PA-III cell CM hydrolyzed IGFBPs of UMR 106 cells and stimulated the proliferation of UMR 106 cells in serum-free cultures. Its protease activity was abolished by benzamidine and aprotinin. Its mitogenic activity for osteoblasts was inhibited by anti-IGF-I monoclonal antibody. Northern blot analysis documented the expression of the urokinase-type plasminogen activator gene in the mRNA extracted from PA-III cells. Urokinase expression was inhibited by dexamethasone. Therefore, we conclude that urokinase-type plasminogen activator stimulates osteoblasts via an IGF-I dependent mechanism. Hydrolysis of the IGFBOPs at the sites of PA-III cell-induced bone tumors account for an increased bioavailability of IGFs. This may facilitate the development and the growth of PA-III cell-induced bone tumor and can also mediate the subsequent local osteoblastic reaction.

Animals↗