PubMed Health⌕ Search

Biomedical subjects

S A Berry

Publications and source records attributed to S A Berry.

At least 73 records · Page 4Linked to original sources

Effects of elevated serum insulinlike growth factor-II on growth hormone and insulinlike growth factor-I mRNA and secretion.

The insulinlike growth factors (IGF) appear to exert feedback control over their own production. In an effort to determine the physiologic mechanisms for this feedback modulation, we utilized a previously developed in vivo model in which rIGF-II secreting tumor cells are transplanted into immunodeficient rats to form IGF-II secreting tumors. The tumor-bearing rat have serum IGF-II concentrations sevenfold greater than those in controls (119 +/- 16 ng/mL [mean +/- SE] v 17 +/- 2 ng/mL, P less than .0001). Serum IGF-I concentrations were reduced among the tumor-bearing rats (438 +/- 42 ng/mL v 606 +/- 32 ng/mL, P = .002) and were negatively correlated with IGF-II concentrations (r = -.47, P = .025), suggesting that IGF-II suppressed the secretion of IGF-I. Increased serum IGF-II concentrations, however, did not affect basal growth hormone concentrations (tumor-bearing, 44 +/- 12 ng/mL; control 33 +/- 6 ng/mL, P = 0.96). The GH response to GH releasing factor was likewise similar in both groups. Moreover, pituitary GH mRNA level were not different in the two groups, suggesting that IGF-II does not have a significant effect on GH secretion in this in vivo model. There was no association between serum glucose and serum IGF-I or IGF-II concentrations. To examine the effect of IGF-II on IGF-I production from the liver, we measured IGF-I mRNA levels in a subset of animals. Despite these differences in serum IGF-I concentrations, the tumor-bearing rats did not have significantly lower liver IGF-I mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neurotensin activates tuberoinfundibular dopamine neurons and increases serum corticosterone concentrations in the rat.

The activity of tuberoinfundibular dopamine neurons, as estimated from the amount of dihydroxyphenylalamine (DOPA) formed in the median eminence after the inhibition of DOPA decarboxylase and the concentration of dihydroxyphenylacetic acid (DOPAC) in this brain region, was significantly increased 1-8 h following the intracerebroventricular (i.c.v.) administration of neurotensin (20 micrograms). Neurotensin (5 and 20 micrograms i.c.v.) also significantly increased DOPAC concentrations in the n. accumbens but had no effect in the striatum. Serum concentrations of corticosterone in rats treated with neurotensin (1-20 micrograms i.c.v.) were 5-7 times those in vehicle-treated animals. [D-Trp11]-neurotensin (0.5 micrograms i.v.c.) also significantly increased DOPAC concentrations in the median eminence and serum corticosterone concentrations. It is concluded that neurotensin acutely increases the activity of tuberoinfundibular and mesolimbic dopamine neurons and the secretion of ACTH.

3,4-Dihydroxyphenylacetic Acid↗

Growth failure in cholestatic rats: the effect of malnutrition on insulin-like growth factor I.

Low IGF-I levels are found in patients with chronic liver disease, but it is not known whether these reductions in IGF-I are secondary to hepatic dysfunction or to malnutrition. To determine whether malnutrition associated with hepatic dysfunction causes the decrease in these levels, serum and liver IGF-I concentrations and liver IGF-I mRNA content were compared in three groups of Sprague-Dawley rats: 15 rats underwent bile duct obstruction; 10 rats were sham-operated and pair-fed with operated rats to control for nutritional status; and 12 rats were sham-operated controls fed ad libitum. In addition, IGF-I peptide and mRNA were compared with food intake, crude nitrogen balance, total wt gain, tail length increase and leg muscle wt. All the parameters were lower in cholestatic and nutritionally deprived animals than in control animals (p less than 0.001). There was no difference in serum and hepatic IGF-I and liver IGF-I mRNA values between the 10 cholestatic and pair-fed animals, despite lower crude nitrogen balance, tail length gains, and leg muscle wt in the bile duct-obstructed animals. These studies suggest that in chronic bile duct obstruction, the low serum and hepatic IGF-I levels are primarily due to decreased food intake and appear unrelated to cholestatic liver disease itself. However, factors in addition to suboptimal nutrition and decreased IGF-I levels must also contribute to cholestasis-induced growth failure.

Animals↗

Actions of typical and atypical antipsychotics on tuberoinfundibular dopamine neurons.

The activity of tuberoinfundibular dopamine neurons, as judged from the accumulation of dihydroxyphenylalanine (DOPA) after the inhibition of decarboxylase activity, was unaltered following the acute administration of the typical antipsychotics haloperidol, cis-flupentixol, chlorpromazine, or fluphenazine. In contrast, a significant increase in the activity of tuberoinfundibular dopamine neurons was elicited by the purported atypical antipsychotics clozapine, melperone, thioridazine, setoperone, and RMI 81582. The clozapine-induced increase in the activity of tuberoinfundibular dopamine neurons was antagonized by the D1 agonist SKF 38393, but not by the D2 agonist quinpirole. The stimulatory effects of atypical antipsychotics on the activity of these hypothalamic dopamine neurons was mimicked by neurotensin and its analogue [D-Trp11]-neurotensin. Moreover, like typical antipsychotics, neurotensin and its analogue also increased serum concentrations of corticosterone. The production of an acute activation of tuberoinfundibular dopamine neurons, which is sensitive to D1 receptor activation and may be mediated by neurotensin, appears to be an effect that distinguishes typical and atypical antipsychotics.

Animals↗

A deficiency of both subunits of pyruvate dehydrogenase which is not expressed in fibroblasts.

Pyruvate dehydrogenase complex (PDC) deficiency usually has been detected by decreased activity in cultured skin fibroblasts. We investigated two brothers in whom PDC activity was less than 10% of controls in lymphocytes but normal in skin fibroblasts. They both had abnormal neuromuscular development and lactic acidosis which was aggravated by ingestion of carbohydrate. One brother died at age 3 yr and tissues were obtained at autopsy soon after death. The brain was swollen with diffuse acute hemorrhages but without the lesions characteristic of Leigh's disease. PDC activity was virtually undetectable in mitochondria or homogenates of liver, skeletal muscle, and heart, but was about 30% of controls in kidney. The activity of the first component E1 was not detectable in mitochondria from liver, whereas the activities of the second and third components were normal; the activities of all components were normal in fibroblasts. Western immunoblot analysis showed absent to trace amounts of both the E1 alpha and E1 beta subunits in liver, skeletal muscle, and heart, with normal amounts of the second and third components. About one-fourth of control amounts of E1 alpha and E1 beta were present in kidney and normal levels were present in fibroblasts. PDC activity in lymphocytes from the mother was 35% of controls; she had normal PDC activity in her fibroblasts. PDC activity was normal in lymphocytes from the brothers' sister, father, and maternal grandparents and great-grandmother. The mode of inheritance was not established. In conclusion, PDC deficiency may not be detected in skin fibroblasts in some cases; the mechanism of variable tissue expression of E1 remains to be delineated.

Child, Preschool↗

Identification of a rat GHRH-like substance and its messenger RNA in rat testis.

The adult testis is a source of hypothalamic neuropeptides including TRH, GnRH, POMC and CRF. The role of these neuropeptides as paracrine regulators of gonadal function in the testis remains unknown. We postulated that growth hormone releasing hormone (GHRH) might also be measureable in rat testis. Testes from ten post pubertal rats (400-425g, approximately 90d) were extracted and assayed in an enzyme linked immunosorbent assay (ELISA) which utilized an anti-rat GHRH antiserum and had a sensitivity of 30 pg. We detected 1.62 +/- 0.17 (M +/- SEM) ng of GHRH-like substance per g testis. The GHRH content of hypothalamus from these animals was 2.70 +/- 0.24 ng/g (N = 7.6 hypothalami/N). Fat served as a negative control tissue in which no GHRH-like material was detectable. To confirm the finding and in attempt to determine if it represented local production of GHRH, we measured GHRH mRNA using a cRNA probe subcloned from a cDNA for rat GHRH. Abundant levels of hybridizing RNA were found in mature testis by dot-blot hybridization (319% +/- 30% of the mean hypothalamus value). Northern analysis revealed that the rat hypothalamic GHRH mRNA was 715 nucleotides. In contrast, testicular GHRH(-like) mRNA was 1750 nucleotides. We conclude that there are high levels of a GHRH-like substance in mature rat testis which is present both at the level of protein product and gene transcript. The mRNA for this GHRH-like substance is substantially larger than the GHRH transcript from hypothalamus.

Animals↗

Hormonal regulation of serum alpha 1-antitrypsin and hepatic alpha 1-antitrypsin mRNA in rats.

We evaluated the effects of pituitary dependent hormones on alpha 1-antitrypsin in male rats. Hepatic alpha 1-antitrypsin mRNA was measured by in vitro translation and by specific hybridization with a mouse cDNA alpha 1-antitrypsin probe. Hypophysectomy caused a 50-75% decrease in serum elastase inhibitory capacity (measuring functional alpha 1-antitrypsin) and hepatic alpha 1-antitrypsin mRNA content. In hypophysectomized animals, no increase in elastase inhibitory capacity or alpha 1-antitrypsin mRNA levels by translation was found when met-human growth hormone alone or corticosterone, dihydrotestosterone and thyroxine were given together. Growth hormone increased alpha 1-antitrypsin mRNA by hybridization to a small extent. Addition of growth hormone to the combination of corticosterone, dihydrotestosterone, and thyroxine increased serum elastase inhibitory capacity and alpha 1-antitrypsin mRNA. We conclude that growth hormone acts synergistically with the other pituitary dependent hormones to regulate serum and hepatic mRNA levels of alpha 1-antitrypsin.

Animals↗

Medical genetics for clinicians. 1. Recent advances in diagnostic technology.

During the last 15 years, the potential for diagnosis and treatment of genetic disorders has rapidly expanded. In general, patients with multisystem abnormalities that include retarded physical growth and delayed development are candidates for chromosome analysis. Because failure to consider a genetic cause for a disorder can be disastrous, physicians need to familiarize themselves with genetic principles and new genetic technology.

Base Composition↗

Methionyl- and pituitary derived human growth hormone have identical effects on the expression of growth hormone responsive rat hepatic mRNA.

Pituitary extracts of human growth hormone have been used extensively for therapy of growth hormone deficiency, although they are known to contain a variety of contaminating polypeptides. Biosynthetic human growth hormone is now available for this use and appears to be functionally identical in promoting growth. To establish additional criteria of identity we compared the effect of these two hormone preparations on a family of hepatic messenger RNA sequences in hypophysectomized adult male rats. Total hepatic RNA from these animals was translated in a cell-free rabbit reticulocyte lysate. Five translational products previously demonstrated to be responsive to ovine and methionyl-human growth hormone were found to be equally induced by pituitary derived human growth hormone, despite demonstrable heterogeneity in pituitary derived preparations. In addition, no significant alterations in approximately 200 non-growth hormone responsive translational products were identified. Methionyl and pituitary derived growth hormone have identical effects on the expression of hepatic mRNA.

Animals↗

Differential endocrine regulation of alpha 2U-globulin messenger ribonucleic acid activity: effect of age at hypophysectomy.

Three alpha 2U-globulin products were identified on two-dimensional gel electrophoretograms of the [35S]methionine-labeled products formed in response to total hepatic RNA by the reticulocyte lysate translational assay. These products, arbitrarily designated A, B, and C, were quantified by video-imaging of two-dimensional electrophoretograms. At both 65 and 85 days, they represent approximately 13%, 10%, and 77%, respectively, of the total translational products coding for alpha 2U-globulin. Hypophysectomy at either 30 or 55 days resulted in a marked decrease in all three products when measured at 60 and 85 days. Products A and B were not induced in animals hypophysectomized (hypox) at 30 days and subsequently reinjected for 10 days beginning on day 50 with GH alone; with T4, corticosterone, and dihydrotestosterone (three hormones); or with a four-hormone combination. Product C was significantly induced by the four-hormone combination. In animals hypox at 55 days and reinjected for 10 days beginning on day 75, GH alone and the three-hormone combination failed to increase product A. In contrast to the observations in animals hypox at 30 days, the four-hormone combination induced a significant increase in products A and B in animals hypox at 55 days, and product C was induced by the three-hormone as well as the four-hormone combination. Measurement of total alpha 2U-globulin mRNA by cDNA hybridization indicated that animals hypox at 30 days achieved only 33.8% of age-matched normal levels, whereas animals hypox at 55 days achieved 69% (P less than 0.05) when injected with all four hormones. Furthermore, the three-hormone combination increased total alpha 2U-globulin mRNA in animals hypox at 55 days, but not in animals hypox at 30 days. The observations on the individual alpha 2U-globulin products suggest that endocrine regulation of individual alpha 2U sequences is not identical. The different magnitude of response observed in the animals hypox at different ages suggests that exposure of the liver to a pituitary-dependent factor between 30 and 55 days modifies the ability of the liver to regulate alpha 2U-globulin mRNA levels.

Aging↗

Ontogenesis of growth hormone (GH)-responsive hepatic gene products: lack of correlation with hepatic GH receptor content.

The ontogenesis of hepatic GH receptor content is postulated as a major determinant of expression of hepatic GH-responsive gene products, since the ontogeny of the receptors and the responsive gene products, somatomedin-C, somatomedin-binding protein, and GH-responsive acidic protein, have similar qualitatively ontogenetic patterns. Two-dimensional gel electrophoresis of in vitro synthesized [35S]methionine-labeled proteins formed in the cell-free mRNA-dependent rabbit reticulocyte lysate system in response to hepatic RNA was used to quantitate the ontogenetic changes in a family of five GH-responsive gene products (S3, S11, S15, S16, and S20). These gene products were altered 2- to 12-fold by the administration of methionyl-human GH to adult hypophysectomized animals and were not altered by the combined administration of T4, corticosterone, and dihydrotestosterone. The translational activity of three of the five products (S3, S15, and S20) in animals younger than 15 days ranged from 1-12% of the values observed in normal adults and was consistent with diminished GH action. The translational activities of two mRNA sequences (S11 and S16) were not consistent with diminished GH action in the newborn animal. In the newborn animal, S11, induced 3-fold by GH in the adult animal, was 7.4 times the level observed in the adult. During the time of increasing GH receptor content (2-35 days), S16, attenuated by GH 2-fold in the adult, increased 6-fold. Injection of GH from days 2 through 11 augmented S20 and D2 (a hormonally nonresponsive, developmentally dependent product) 2-fold. The combined administration from days 2 through 11 of GH, T4, and corticosterone augmented S16 1.8-fold, a response paradoxical to that in the adult animal, but consistent with advancing maturation of the liver. We conclude that GH receptor content is not the sole determinant for the ontogenetic expression of GH-responsive products and that important alternate mechanisms exist for their regulation. In addition, GH, along with T4 and corticosterone, appear to modulate the rate at which adult levels of some mRNA sequences are achieved.

Animals↗

Agenesis of the penis, scrotal raphe, and anus in one of monoamniotic twins.

Severe defects in the development of the caudal axis are rare, but lead to profound consequences for the fetus. They result from damage to multiple germ layers at a very early stage of development and vary in severity depending on the timing and degree of insult incurred. One of a set of identical male twins presented with persistence of the primitive cloaca with an absent phallus and anal atresia, but normal limb development. This combination of penile agenesis, imperforate anus, and absence of the scrotal and perineal raphae is an ominous physical finding indicative of severe renal anomalies, which in all cases have been incompatible with extrauterine survival. This constellation of findings, of which our patient is only the sixth reported example, probably results from a primary defect in caudal mesoderm migration before the fourth week of gestation. In this case, the defect may have occurred as a consequence of monochorionic monoamniotic monozygotic (MZ) twinning.

Abnormalities, Multiple↗

Single central incisor in familial holoprosencephaly.

Most cases of holoprosencephaly occur sporadically, but occasionally this malformation recurs in a kindred. In a family with two affected children, the father and paternal aunt were found to have single central maxillary incisors and hypotelorism. Family members of children with holoprosencephaly should be carefully examined for these physical findings; their presence may represent evidence for a less severe form of holoprosencephaly that may be transmitted in an autosomal dominant fashion.

Brain↗

Substantial induction of a new serum protein by growth hormone: physiochemical and physiological characterization.

Serum from GH-treated hypophysectomized rats was examined by two-dimensional gel electrophoresis followed by silver staining to screen a large number of serum proteins for GH responsiveness. A distinctive, highly acidic protein of 60,000 mol wt was clearly responsive to GH administration, increasing 7-fold over levels observed in hypophysectomized controls. Administration of T4, corticosterone, and 5 alpha-dihydrotestosterone failed to induce this protein; however, addition of GH to this regimen resulted in a 60-fold increase in its concentration. Examination of proteins synthesized by isolated hepatocytes in the presence of [35S]methionine showed that this protein is of hepatic origin. Physiological and physiochemical evidence suggest that this protein is unlikely to be one of the other well documented GH-responsive serum proteins: somatomedin-C, alpha 2U-globulin, or the somatomedin-binding protein. The protein demonstrates a remarkable ontogeny, increasing 135-fold over newborn levels by 35 days of age. This is qualitatively similar to changes observed in somatomedin-C, however, the quantitative change is much more striking. Examination of the protein in an altered physiological state which limits growth (uremia) reveals a 30-fold diminution of levels of the protein after 3 weeks of renal failure. In contrast, pair-fed animals demonstrated only a 2-fold decrease. This suggests that there is a profound inhibition of GH action which is not accounted for by poor nutritional intake. This protein may be useful in the investigation of the GH-hepatic axis.

Age Factors↗