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R J Robbins

Publications and source records attributed to R J Robbins.

At least 73 records · Page 4Linked to original sources
PubMed1986

Immunohistochemical localization of GRF-containing neurons in rat brain.

Brains from 4 normal and 4 colchicine-treated rats were studied for the presence of growth hormone-releasing factor (GRF) using an antibody directed against rat hypothalamic GRF (rGRF). Noncolchicine-treated animals showed intense staining in the external layer of the median eminence. Rats pretreated with intraventricular colchicine for 48 h showed localization of GRF-containing cell bodies in the arcuate nucleus, the perifornical area, the lateral basal hypothalamic region and lateral to the ventromedial nucleus and the premammillary nucleus. This pattern of distribution is consistent with the postulated role of GRF in hypothalamic regulation of growth hormone secretion. Our results confirm the predominant localization of GRF perikarya in the arcuate nucleus of the rat which has been noted in studies using antibodies directed against both human pancreas GRF (hpGRF) and rGRF, and demonstrate a unique pattern of rGRF-positive cell bodies elsewhere in the hypothalamus. No rGRF perikarya or processes were seen outside the hypothalamus.

Animals↗
PubMed1986

Syndrome of inappropriate antidiuresis in the absence of arginine vasopressin.

The syndrome of inappropriate antidiuresis (SIAD) is usually associated with inappropriately elevated plasma arginine vasopressin (AVP) concentrations. We describe herein a patient with a macroprolactinoma who had symptomatic hyponatremia due to SIAD. Although the patient had excessive thirst, severe plasma hypoosmolality, and hyperosmolar urine, no immunoassayable AVP could be detected. During long term treatment with bromocriptine, there was gradual shrinkage of the prolactinoma coincident with improvement in the ability to excrete a water load and normalization of the thirst threshold. At this point, plasma immunoactive AVP was measurable during a hypertonic saline infusion for the first time. By high pressure liquid chromatographic analysis, this immunoactive substance coeluted with AVP. These studies suggest that the SIAD in this patient was due to the production of an antidiuretic substance distinct from AVP in association with his prolactinoma.

Adult↗
PubMed1986

Regional distribution of human growth hormone-releasing hormone in the human hypothalamus by radioimmunoassay.

The regional distribution of human GH-releasing hormone (hGHRH) in the hypothalamus was determined by RIA using a standardized microdissection technique. The antiserum used in the RIA is highly specific for human GHRH-44, and cross-reactivity to hGHRH-40 is minimal (less than 0.06%). The concentration and content of immunoreactive hGHRH-44 (IR-GHRH) were measured in extracts of 12 nuclei and areas microdissected from hypothalami from 5 autopsy subjects. Extracts of proximal and distal pituitary stalk were similarly analyzed for IR-GHRH. The highest concentration of IR-GHRH in the hypothalamus was in the infundibular nucleus, with lesser concentrations in the periventricular area and paraventricular and supraoptic nuclei. All other regions had measurable concentrations, except the mammillary nuclei. There was 56.1 +/- 12.4 (+/- SD) ng (11.1 +/- 1.2 pmol) IR-GHRH in the human hypothalamus and pituitary stalk, with 62% in the pituitary stalk. IR-GHRH in tissue extracts produced the same dose-response curve as did hGHRH in the RIA and coeluted with synthetic hGHRH-44 on gel filtration. Our results indicate the following. 1) The regional distribution of IR-GHRH in the human hypothalamus differs from the regional distributions of other neuropeptides. 2) The infundibular nucleus contains the greatest IR-GHRH regional concentration, in accord with immunohistochemical studies. 3) Appreciable concentrations of IR-GHRH are found in regions not previously identified by immunohistochemical techniques. 4) The IR-GHRH molar content in the hypothalamus-pituitary stalk is lower than that reported for other hypothalamic releasing hormones.

Adult↗
PubMed1985

The effects of neurotensin, vasoactive intestinal polypeptide and other neuropeptides on the secretion of somatostatin from cerebral cortical cells.

We have examined the effects of several neuropeptides on the release of immunoreactive somatostatin from cerebral cortical cells in vitro. Neurotensin and vasoactive intestinal polypeptide induced large increases in somatostatin release, whereas cholecystokinin, gonadotropin releasing hormone and Met-enkephalin induced only modest increases. Thyrotropin releasing hormone and insulin had no effect. These results demonstrate a complex interaction amongst neuropeptides in the cerebral cortex, which must be considered in future studies of the roles of peptides in cortical function.

Animals↗
PubMed1985

The effects of growth hormone, prolactin, corticotropin, and thyrotropin on the production and secretion of somatostatin by hypothalamic cells in vitro.

The influence of GH and several other pituitary hormones on the secretion and intracellular content of immunoreactive somatostatin (IRS) in cultured hypothalamic cells was examined. Hypothalamic cells prepared from 17-day-old rat embryos and maintained as reaggregate monolayers for 12 days in vitro were used. Short term release of IRS from these cultures was found to be stable and relatively constant. IRS release was enhanced by 60 mM K+ in a calcium-dependent fashion and by dopamine at concentrations as low as 1 nM. GH (1 microM) increased medium IRS content above baseline 12, 24, and 48 h after the incubation was begun, but had no effect after only 4 h. Hypothalamic cell content of IRS was increased by a 24-h incubation in 0.3 and 1.0 microM GH, but not by 0.1 microM GH. TSH (1 microM) induced an increase in IRS release comparable to 1 microM GH. However, intracellular IRS content was decreased after exposure to TSH. Cosyntropin, an ACTH analog, inhibited both IRS release and cell content, whereas PRL had no effect on either medium or cellular IRS content. Our results demonstrate that developing somatostatinergic neurons in the hypothalamus have the capacity to respond to pituitary hormones, indicating that short-loop feedback pathways may exist in perinatal hypothalamic cells.

Adrenocorticotropic Hormone↗
PubMed1985

Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study.

To assess the effectiveness of bromocriptine in reducing the size of PRL-secreting macroadenomas with extrasellar extension, we conducted a prospective multicenter trial in patients without prior radiotherapy, applying a standard protocol of treatment and tumor size evaluation. Basal serum PRL levels [1441 +/- 417 (+/- SEM) ng/ml for women; 3451 +/- 1111 ng/ml for men] fell in all patients and to 11% or less of basal values in all patients but 1. Normal PRL levels were reached in 18 of the 27 patients. In 13 patients (46%), tumor size was reduced by greater than 50%, in 5 patients (18%) by about 50%, and in 9 patients (36%) by approximately 10-25%. The extent of tumor size reduction did not correlate with basal PRL, nadir PRL, percent fall in PRL, or whether PRL levels reached normal. However, a reduction in PRL levels always preceded any detectable change in tumor size. In 19 patients, reduction in tumor size was evident by 6 weeks, but in the other 8, such reduction was not noted until the 6 month evaluation. In the 4 patients in whom bromocriptine was discontinued at the end of 1 yr, tumor reexpansion occurred in 3. Visual fields improved in 9 of the 10 patients in whom they were abnormal. Because of the excellent results found in most of the patients in this series, we suggest that therapy with bromocriptine should be considered as initial management for patients with PRL-secreting macroadenomas.

Adenoma↗
PubMed1984

Interactions between thioridazine and bromocriptine in a patient with a prolactin-secreting pituitary adenoma.

Reported herein is the possible interaction between two drugs used to treat a man with a large prolactin-secreting pituitary adenoma. The patient had a long history of schizophrenia that was treated with many different medications, including phenothiazines. Evaluation of progressive lethargy led to the discovery of a large parasellar tumor and a prolactin level of 7,981 ng/ml. His serum prolactin level fell to the 400 ng/ml range during bromocriptine therapy but rose whenever the antipsychotic thioridazine was added to his regimen. A marked deterioration of his visual fields was noted after 3 months' therapy with both drugs, and this abnormality resolved five days after the thioridazine was stopped. The use of dopamine antagonists such as thioridazine in patients with prolactinoma may interfere with bromocriptine's action, resulting in potentially serious complications.

Adenoma↗
PubMed1984

Lipoprotein lipase is produced, regulated, and functional in rat brain.

Lipoprotein lipase (LP lipase, triacylglycero-protein acylhydrolase EC 3.1.1.34) activity was found in four dissimilar brain regions (hypothalamus, cortex, cerebellum, and midbrain) of adult male rats. Progressive accumulation of LP lipase activity in cultured fetal rat hypothalamic cells was also observed, indicating de novo synthesis of the lipase. The brain LP lipase activity was serum-dependent and was inhibited by 1 M NaCl and by protamine sulfate. Kinetic analysis revealed an apparent Km of 0.79 mM very similar to that of rat adipose tissue LP lipase. That the lipase was functioning in the cultured brain cells was indicated by uptake and incorporation of radioactivity from tri[( 1-14C]oleoyl)glycerol into cellular triacylglycerols, and into more polar lipids, such as phosphatidylcholine. Furthermore, brain LP lipase activity in adult rats was decreased in all four regions examined, most significantly in the hypothalamus, after 72 hr of food deprivation. Thus, authentic LP lipase is present in adult rat brain and can be synthesized by isolated brain cells in vitro. LP lipase also mediates the uptake of triacylglycerol fatty acids and their subsequent incorporation into cellular lipids of cultured brain cells. Decreased brain LP lipase activity after fasting suggests that this enzyme may be regulated by metabolic or nutritional factors. Because the largest changes in LP lipase activity in response to food deprivation occurred in the hypothalamus, the enzyme may have a role in hypothalamic control of food intake or in body-weight regulation.

Animals↗
PubMed1983

Somatostatin release from cerebral cortical cells: influence of amino acid neurotransmitters.

We examined the ability of several putative amino acid neurotransmitters to influence immunoreactive somatostatin (IRS) release from cultured rat cerebral cortical cells. The cells were exposed to either or sequential incubations in various concentrations of glutamate (Glu), aspartate (Asp), GABA, glycine, taurine and arginine. Glu and Asp were stimulatory to IRS release, whereas GABA was inhibitory. Glu-induced IRS release was calcium-dependent. Glycine and taurine were weak stimulants.

Amino Acids↗
PubMed1983

Influence of glucose on somatostatin synthesis and secretion in isolated cerebral cortical cells.

Somatostatin-producing cerebral cortical cell cultures were grown in either high- (33 mM) or low-glucose (5 mM) medium and then exposed to short repetitive changes of high- or low-glucose Krebs-Ringer's bicarbonate buffer. Equivalent amounts of somatostatin were released in the high-to-high, the low-to-low, and the low-to-high paradigms. The high-to-low experiment produced a rapid rise in somatostatin release, followed by a decline. Cultures exposed to 2-deoxyglucose after high-glucose medium also released much greater amounts of immunoreactive somatostatin. Separate sets of cultures were grown in high- or low-glucose medium for up to 19 days. Cultures grown in high-glucose medium generally contained more somatostatin intracellularly than did those maintained in low glucose, although somatostatin in the medium was only different at day 19. These results identify extracellular glucose as an important determinant of cortical somatostatin production.

Animals↗
PubMed1983

Characterisation of somatostatin and TRH release by rat hypothalamic and cerebral cortical neurons maintained on a capillary membrane perfusion system.

We have investigated the nature of the immunoreactive somatostatin (SS) and thyrotropin-releasing hormone (TRH) produced by long-term capillary perfusion cultures of rat fetal cortical and hypothalamic cells. Dispersed cortical and hypothalamic cells from 17-day-old fetal rats were injected on to the outer surfaces of separate capillary membrane perfusion systems. Recirculating nutrient medium (Minimum Essential Medium with added glucose, antibiotics and 10% fetal calf serum) was then perfused via the capillary lumen at a rate of 1.5 ml/min and was changed three times weekly. Medium reservoirs, gaseous exchange coils and capillary columns were maintained in a 95% air/5% CO2 environment with 100% humidity. After 6 and 12 days in continuous perfusion, both cortical and hypothalamic cells demonstrated immuno-reactive SS release following 60 mMK+ depolarization (5- to 7-fold increase from basal secretion levels of 15-20 pg/3 X 10(7) cells/10 min). This response was clearly calcium dependent since it was abolished during washes with Ca2+-free Krebs-Ringer bicarbonate solution. Affinity purified material from pooled neuronal perfusates showed three distinct peaks of somatotropin release-inhibiting factor (SRIF) immunoreactivity following polyacrylamide gel chromatography on Biogel-P10. The dominant form coeluted with synthetic tetradecapeptide-somatostatin (SS-14) and a smaller amount (c 30%) coeluted with synthetic SS-28. (The SS-14 antibody used showed equimolar cross reactivity with SS-28). A larger form of immunoreactive material was also detected with an apparent molecular weight of about 11,500 daltons. Hypothalamic and cortical perfusates produced similar electrophoretic patterns of immunoreactive SS (ISS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Somatostatin biosynthesis by cerebral cortical cells in monolayer culture.

We examined the ability of isolated rat cerebral cortical cells to synthesize and secrete immunoreactive somatostatin (IRS). Dispersed telencephalic cells (10(7] from rat embryos contain approximately 24 pg IRS. The IRS content of 10(7) cultured cells increased steadily to a level of 2800 pg by 20 days in vitro. The IRS content in the medium followed a parallel production curve and was, in general, 10% of the cellular content. The nature of this IRS was characterized by gel filtration. Bio-Gel P-10 chromatography resolved four discrete IRS peaks. The first peak had an apparent molecular weight of 11,500. The second peak, which comigrated with synthetic Somatostatin-28, had a molecular weight of 7,000. The third peak had a molecular weight of 1,800, and the fourth peak, which comigrated with Somatostatin-14, had a molecular weight less than 1,800. Incubation with [3H]phenylalanine (Phe) revealed that 3H was incorporated into each peak. Isolation of 3H-labeled peak 4 was carried out by double affinity column purification. Sequential automated Edman degradation of this material revealed [3H] Phe in the positions that Phe occupies in Somatostatin-14. These studies document the ability of isolated rat cerebral cortical tissue to synthesize several forms of IRS, establishing them as endogenous cortical peptides.

Amino Acid Sequence↗
PubMed1983

Unilateral toxic multicystic goiter.

We treated a 43-year-old woman who had multiple thyroid cysts and coexistent toxic nodules localized to the left lobe. After surgical excision of this lobe, the patient's right lobe proceeded to function normally, displaying no evidence of nodules, cysts, or hyperfunction. Since toxic multinodular goiter is usually a diffuse process involving the whole gland, this case is unique and underlines the wide variability in the manifestation of this disorder.

Adult↗
PubMed1982

Effects of neurotransmitters and cyclic AMP on somatostatin release from cultured cerebral cortical cells.

The influence of cortical neurotransmitters and cyclic AMP on the release of immunoreactive somatostatin (IRS)from cultured cortical cells was examined. Cells were obtained by mechanoenzymatic dispersal of telencephalons of 17-day-old rat embryos and were maintained as monolayers in minimum essential medium with 10% heat-inactivated horse serum. After the cultures had stabilized morphologically and in cellular IRS content they were subjected to rapid sequential changes of a buffered salt solution with or without test substances added. The amount of somatostatin released was measured by a specific radioimmunoassay. Acetylcholine and the GABA antagonist, picrotoxin, both stimulated IRS release. The cholinergic stimulation was predominantly muscarinic. GABA and histamine, to a lesser extent, were inhibitory and norepinephrine and serotonin produced no net change in IRS release. Both cAMP and theophylline (DMX) stimulated IRS release. These results confirm the potential of intrinsic cortical somatostatinergic neurons to respond to endogenous neurotransmitters and further establishes somatostatin as a cortical neuromodulator.

Acetylcholine↗
PubMed1982

Sodium- and calcium-dependent somatostatin release from dissociated cerebral cortical cells in culture.

The influence of membrane depolarization on somatostatin release from cerebral cortical neurons was examined. Fetal rat telencephalic cells, obtained by mechanoenzymatic dispersal, were maintained as organotypic monolayer cultures for 12 days before experimental studies. The immunoreactive somatostatin (IRS) released into the medium during a treatment epoch was compared to the amount released from the same cells during an immediately preceding control period. Potassium (60 mM) induced an increase in IRS secretion which was dependent on extracellular calcium concentration and could be prevented by the addition of the calcium channel blockers, cobalt or verapamil. Depolarization by veratridine, a sodium ionophore, also stimulated IRS release. The effect of veratridine was reversed by simultaneous exposure of the cells to either tetrodotoxin, a sodium channel blocker, or verapamil, a calcium channel blocker. These findings indicate that IRS release by cerebral cortical cells is stimulated by membrane depolarization and is dependent on both Na+ and Ca++ entry into the cells.

Animals↗
PubMed1980

Direct observation of the torsional dynamics of DNA and RNA by picosecond spectroscopy.

Picosecond time-dependent fluorescence depolarization techniques have been used to monitor the reorientation of ethidium bromide intercalated in DNA and RNA. The fluorescence polarization anisotropy reveals a nonexponential, exp(-at 1/2), torsional relaxation of the DNA double helix and provides an accurate value for its torsional rigidity, C = 1.3 +/- 0.2 X 10(-19) erg cm. Furthermore, from accurate measurements of the limiting anisotropy at zero time, we conclude that there is an additional fast (< 10 psec) internal motion that depends on the viscosity of the medium. Denatured DNA is considerably more flexible than the intact double helix, thus demonstrating the influence of secondary structure on internal motions.

DNA↗