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Biomedical subjects

J A Edwardson

Publications and source records attributed to J A Edwardson.

At least 127 records · Page 7Linked to original sources
PubMed1975

Release of corticotrophin releasing factor and other hypophysiotropic substances from isolated nerve-endings (synaptosomes).

Synaptosomes isolated from the sheep and the rat hypothalamus contain corticotrophin releasing factor, vasopressin, prolactin-release inhibiting factor and probably all of the substances which participate in the regulation of adenohypophysial function. Electrical field stimulation or depolarizing concentrations (55 mmol/l) of potassium ions cause a release of these factors from the incubated nerve-endings in a calcium-dependent manner. It is suggested that synaptosomes may provide a valuable approach to the study of mechanisms involved in hypothalamic neurosecretion in vitro.

Adrenocorticotropic Hormone↗
PubMed1975

The pituitary-adrenal system of the genetically obese (ob/ob) mouse.

Adult genetically obese (ob/ob) mice which are characterized by adrenal hypertrophy and increased secretion of corticosteroids have considerably increased levels of ACTH in the pituitary gland. At 5 weeks of age there is no difference in the pituitary ACTH content of lean and obese animals and dietary restriction, sufficient to maintain body weight at normal values, reduces the pituitary ACTH content of adult obese mice from 14 times the level found in lean litter-mate controls to almost normal values. Using an in-vitro perifusion system, the release of ACTH from isolated pituitary glands was studied. Pituitaries from lean and obese mice responded similarly to stimulation with a crude extract of hypothalamic tissue containing coticotrophin releasing factor (CRF). The CRF content of the hypothalamus in both groups appears to be similar. In contrast with the high pituitary content, plasma values for ACTH in unstressed obese mice are not increased. The results are discussed in relation to other evidence for a hypothalamic disorder in ob/ob mice.

Adrenocortical Hyperfunction↗
PubMed1975

Influence of the pituitary gland on insulin secretion in the genetically obese (ob/ob) mouse.

The influence of the pituitary gland of lean and genetically obese (ob/ob) mice on insulin secretion from microdissected pancreatic islets of lean and ob/ob mice has been studied by perifusing the pituitaries of these animals in series with the isolated islets and measuring insulin secretion at 5-min intervals over a period of 60 min. It has been shown that the pituitary perifusate of both lean and obese mice stimulate insulin secretion from lean mouse islets but not from obese mouse islets. The maximum stimulation occurs in the first 10 min and with the lean mouse pituitaries returns to the basal level in about 20 min, whereas with the obese mouse pituitaries insulin secretion is about double that from the control islets even after 40 min. A concentration of pure porcine ACTH equivalent to about three times the amount released from the pituitary gland under the experimental conditions used, caused only a small stimulation of insulin release. Possible interpretations of these findings and further lines of investigation are discussed.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Brain iron homeostasis.

The anatomical and cellular distribution of non-haem iron, ferritin, transferrin, and the transferrin receptor have been studied in postmortem human brain and these studies, together with data on the uptake and transport of labeled iron, by the rat brain, have been used to elucidate the role of iron and other metal ions in certain neurological disorders. High levels of non-haem iron, mainly in the form of ferritin, are found in the extrapyramidal system, associated predominantly with glial cells. In contrast to non-haem iron, the density of transferrin receptors is highest in cortical and brainstem structures and appears to relate to the iron requirement of neurones for mitochondrial respiratory activity. Transferrin is synthesized within the brain by oligodendrocytes and the choroid plexus, and is present in neurones, consistent with receptor mediated uptake. The uptake of iron into the brain appears to be by a two-stage process involving initial deposition of iron in the brain capillary endothelium by serum transferrin, and subsequent transfer of iron to brain-derived transferrin and transport within the brain to sites with a high transferrin receptor density. A second, as yet unidentified mechanism, may be involved in the transfer of iron from neurones possessing transferrin receptors to sites of storage in glial cells in the extrapyramidal system. The distribution of iron and the transferrin receptor may be of relevance to iron-induced free radical formation and selective neuronal vulnerability in neurodegenerative disorders.

Animals↗
PubMedDate not supplied

Failure of gel filtration and HPLC purification to increase levels of immunoreactive TRH in rat brain extracts.

It has recently been reported [4] that purification of acidified methanol extracts of rat cerebellum by gel filtration and high performance liquid chromatography (HPLC) caused a fifty-fold increase in immunoreactive thyrotrophin-releasing hormone (ir-TRH). However either using Sephadex LH20 or SepPak separation prior to HPLC we have failed to find a significant increase in ir-TRH in rat cerebellar or hypothalamic extracts. We conclude that it is valid to measure TRH by radioimmunoassay in unpurified methanolic extracts of brain tissue.

Animals↗
PubMedDate not supplied

Mechanism of degradation of LH-RH and neurotensin by synaptosomal peptidases.

The products of degradation of LH-RH and neurotensin by synaptosomes isolated from rat hypothalamus and cortex have been identified. LH-RH is cleaved at Tyr5-Gly6 and Pro9-Gly10 giving rise to LH-RH (1-5), LH-RH (6-10) and LH-RH (1-9). Neurotensin is cleaved at Arg8-Arg9, Pro10-Tyr11 and Ile12-Leu13, giving neurotensin (1-8), neurotensin (1-10), neurotensin (1-12) and neurotensin (9-13) as major products. While most of the peptidase activity is localized in the cytoplasmic fraction, a small but significant proportion is membrane bound. For LH-RH, the specificity of the membrane-bound activity is similar to that in the cytosol fraction; for neurotensin, the membrane fraction preferentially gives rise to the (1-10) and (1-11) peptides. The most potent inhibitors of the LH-RH and neurotensin degrading enzymes in synaptosomes are heavy metal ions (mercury and copper), p-chloromercuribenzoate and 1,10 phenanthroline.

Amino Acids↗