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Biomedical subjects

R A Donald

Publications and source records attributed to R A Donald.

188 records · Page 11Linked to original sources

Dexamethasone suppression of the plasma corticosterone response to stress in the rat.

1. The effect of dexamethasone on the plasma corticosterone response to heat-immobilization stress was investigated in male and female rats.2. The plasma corticosterone response of control rats to the type of stress described was 64 mug% (+/- 10.5 mug% standard deviation) in males, and 128 mug% in females.3. A straight line relation between the dose of dexamethasone and the log of the plasma corticosterone response was demonstrated in male rats. The slope of the dose-log response line was used to indicate the degree of suppression of the plasma corticosterone response to stress.4. The straight line relation did not hold for female rats, suggesting the presence of an additional factor or factors which influenced the plasma corticosterone levels.5. An exponential relation between the duration of dexamethasone administration and the slope of the dose-log response line was demonstrated, maximum suppression occurring after an infinite period of time. After 30 days, 95% maximum suppression occurred when the plasma corticosterone response was measured 8 hr after dexamethasone administration had ceased.

Animals↗

Isolated ACTH deficiency confirmed by ACTH radioimmunoassay.

A 28 year old woman presented with symptoms and biochemical findings suggesting hypoglycemia. Detailed endocrine investigations indicated secondary adrenocortical insufficiency with no rise in plasma ACTH or plasma cortisol following insulin-induced hypoglycemia or vasopressin infusion. The adrenal glands however produced cortisol normally following prolonged stimulation with depot tetracosactrin. Other anterior pituitary hormones were released normally following appropriate stimulation tests. The literature on isolated ACTH deficiency is briefly reviewed, and this case represents one of the few reports in which the diagnosis has been substantiated by ACTH radioimmunoassays.

Adrenocorticotropic Hormone↗

An in vivo model for testing somatostatin suppression of growth hormone release in sheep.

To investigate the suppressive effect of somatostatin on growth hormone secretion, a consistent, potent stimulus to growth hormone release is required. The antilipolytic compound 3,5-dimethylpyrazole (DMP) gave a rapid rise in plasma immunoreactive growth hormone following iv administration to fasting sheep. The dose response relationship for iv DMP was defined in 12 sheep, and a rise in growth hormone levels from a baseline of 2.1 +/- 0.4 ng/ml (mean +/- SE) to 38.9 +/- 3.9 ng/ml was achieved in 40 min with 0.1 mg/kg bw of DMP given as a bolus. Infusion of graded doses of somatostatin (50, 100 and 200 micrograms) in 4 sheep over a 90 min period resulted in a dose-dependent suppression of the DMP-provoked growth hormone secretion below the responses observed during saline infusion. This experimental model should facilitate further studies of the inhibitory effects of somatostatin, its analogues and other drugs which suppress growth hormone secretion.

Animals↗

Ectopic secretion of ACTH and met-enkephalin from a thymic carcinoid.

A 51-year old man presented with the classical features of Cushing's syndrome which had evolved over the previous 5 yr, and was found to have ACTH secretion from an atypical thymic carcinoid tumor. Tumor extract, assayed under conditions designed to prevent artefactual generation of peptides, was found to contain a wide variety of immunoreactive hormones including ACTH, alpha-MSH, CLIP, beta-endorphin and met-enkephalin. The ACTH-related peptides were probably derived from a common precursor, pro-opiocortin, but the presence of met-enkephalin suggests the production of a separate type of precursor molecule. The tumor was locally invasive and, depsite subtotal excision and radiotherapy, continued to secrete large amounts of ACTH. Hypercortisolism was controlled longterm with pharmacological adrenal blockade and steroid replacement.

Adrenocorticotropic Hormone↗

A relationship between prolactin levels and dexamethasone suppression test results in major depressive disorder.

Fifteen patients with a major depressive disorder and 20 control subjects have completed a 1 mg Dexamethasone Suppression Test (DST) and on a separate day have had their prolactin and cortisol levels measured at 16.00 h. Among the depressed patients there was a significant positive correlation between the DST cortisol and the prolactin level, with abnormally elevated prolactin levels occurring in those depressed patients with very high DST cortisol (greater than 400 nmol/l) levels.

Adult↗

Individual differences in plasma cortisol changes during mania and depression.

Daytime plasma cortisol levels in four rapid cycling bipolar affective disorder patients were measured longitudinally over multiple affective episodes, and changes in levels with mood state assessed for each individual patient. While three of the four patients had, as expected, increased cortisol levels during depression, higher cortisol levels were also found in the days immediately preceding depressive episodes. Daytime cortisol levels in mania were more variable but were lower in mania for two of the patients. It is hypothesized that in the early stages of mania decreased cortisol levels reflect early neurochemical changes, but that, as manic episodes become dysphoric and/or severe, elevated cortisol levels occur.

Adult↗

The unipolar-bipolar depressive dichotomy and the relationship between afternoon prolactin and cortisol levels.

Afternoon prolactin and cortisol levels were measured in 29 patients suffering from a current major depressive episode. Among the 15 unipolar depressed patients the afternoon prolactin and cortisol levels were positively correlated, but 14 bipolar depressed patients did not show a similar relationship, and had prolactin levels lower than the unipolar patients. This finding adds to the growing list of ways in which the neurobiology of bipolar and unipolar depression may differ.

Adult↗

Structure of equine corticotropin releasing factor.

A 41 amino acid peptide, probably identical in structure to human corticotropin releasing factor, was isolated from 70 equine hypothalami by methanol extraction, immunoaffinity chromatography and single step of reverse phase HPLC. The amino acid sequence was determined by gas phase sequence analysis. Probable carboxyl terminal amidation was demonstrated by similar retention times for equine and human corticotropin releasing factor on reverse phase HPLC at pH 8. The likely structure of equine corticotropin releasing factor is: Ser-Glu-Glu-Pro-Pro- Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg- Ala-Glu - Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2. The purified peptide is equipotent with human corticotropin releasing factor in an in vitro bioassay and in a human plasma binding protein assay.

Amino Acid Sequence↗