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Biomedical subjects

M A Greer

Publications and source records attributed to M A Greer.

At least 127 records · Page 7Linked to original sources
PubMed1976

Distribution of corticotropin releasing factor(s) activity in neural and extraneural tissues of the rat.

Distribution and dose-response characteristics of corticotropin releasing factor(s) (CRF) activity in the central nervous and extraneural tissues of the rat were examined with a sensitive CRF bioassay using ACTH secretion by cultured rat adenohypophyseal cells. Dose-response curves for hypothalamus were steeper than and not parallel to those for cerebral cortex, liver, serum or human urine. The minimum effective dose was smallest for the posterior pituitary. CRF activity of the basal hypothalamus was considerably higher than that in other parts of the hypothalamus, and was unaltered by 2.5 or 10 min ether stress. Our data indicate that "specific" CRF is concentrated primarily in the basal hypothalamus and posterior pituitary and is not identical with widely distributed extrahypothalamic extraneurohypophyseal CRF.

Animals↗
PubMed1976

Further studies on response of blood thyroid hormone level to its acute depletion by isovolemic exchange transfusion.

Groups of rats weighing about 400 g and fed low iodine diet for 16 days were injected with 125I- daily from day 8 to 14. Two days later their blood thyroid hormone was acutely depleted with an isovolemic exchange transfusion of hormone-free blood cell suspension. Relative changes of total plasma radioactivity and iodinated compounds were measured at frequent intervals, maintaining isovolemia of the recipient animal. In normal animals a post-transfusion decrease of total plasma radioactivity was related to the degree of exchange of total blood volume as was the post-transfusion increase to the initial level. No post-transfusion increase of total plasma radioactivity or labeled thyroxine was found in thyreidectomized animals. On the other hand, in normal animals a post-transfusion increase of plasma labelled thyroxine was observed. A linear increase of labeled iodide in plasma was found in both normal and thyroidectomized rats, the mechanism of which in thyroidectomized animals may be explained by a reflux of iodide from peripheral tissues to the blood. In normal animals a TSH-induced release of iodide from thyroid due to TSH action may participate in this phenomenon.

Animals↗
PubMed1975

The effect of iodine deficiency on thyroid function in the infant rat.

We have studied rats born to severely iodine-deficient mothers and subsequently maintained on a low-iodine diet (LID) from birth to 41 days. They were compared with controls born to mothers fed a high-iodine diet (HID). LID babies from birth on had large goiters, high thyroid labeled MIT/DIT ratios and radioiodine uptakes, high plasma TSH and low plasma T4 in comparison to HID controls. Thyroid labeled T3/T4 ratios were low in all babies at birth but were higher in the LID than HID babies from day 5 on and were greater than 1 after day 10, approximating the T3/T4 of the mothers. Coupling efficiency, as indicated by thyroid labeled (T3 + T4)/(MIT + DIT), was relatively low for the first 4 postnatal days for both the HID and LID babies and was associated with a lower plasma T4 than at later intervals. Injection of 0.05 mug 127I- simultaneously with 131I- caused an acute increase in labeled T4 and decrease in MIT formation in LID babies of all ages, but did not affect T3 synthesis. Doses of 127I- 20 times as large had no effect on labeled iodoamino acid synthesis in HID babies. Thyroid organic radioiodine content in newborn LID rats was 65% lower at 24 hr than at 4 hr after 131I injection, indicating that thyroid secretion was occurring. A few of the LID pups were "runts" approximately 60% the size of HID babies the same age. However, the overwhelming majority of LID babies maintained the same weight as HID controls from birth until weaning. After weaning, the LID babies grew at a slower rate than the HID controls. Relative thyroid weight, radioiodine metabolism and plasma TSH were no different in runts of various ages or in their mothers than in the "normal" LID controls. Adaptation was apparently adequate in the LID babies to maintain a nearly euthyroid state. We suggest that the low labeled T3/T4 ratio in the first few days of life in the LID babies may be due to a coupling deficiency in newborn rats resulting in a proportionately greater formation of iodotyrosines than of iodothyronines compared to older animals. This results in a greater intrathyroidal retention of iodine during intracellular thyroglobulin proteolysis and a more highly iodinated thyroglobulin in the LID babies than after normal coupling is achieved.

Animals↗
PubMed1975

Studies on the heterogeneity of labeled iodoprotein from iodine-replete and iodine-deficient rats as determined by susceptibility to proteolysis.

Thyroid iodoprotein from rats fed a high-iodine diet (HID) or a low-iodine diet (LID) were labeled with radioiodine in vivo for periods ranging from 4 hr to several days. Standardized aliquots of thyroid homogenate from rats with various treatments were digested for 4 hr with 1% pancreatin or with 0.003% pancreatin after 30 min pretreatment with beta-mercaptoethanol (ME-P). Four-hr labeled iodoprotein from both LID and HID rats was equally susceptible to digestion with 1% pancreatin; however, such iodoprotein from LID rats was more susceptible to digestion with ME-P than that from HID rats. With increasing intervals up to 7 days between administering radioiodine and removing the thyroids, there was a progressive rise in the resistance to digestion in iodoprotein from LID rats, but only a slight increase in resistance in iodoprotein from HID rats. If propylthiouracil was added to the diet beginning 24 hr after radioiodine administration, there was a marked increase in the rate of development of resistance of iodoprotein to digestion. Radioautographs showed that the radioiodine was localized primarily in the peripheral follicles after 2 days PTU. Similar differences in susceptibility to digestion were found in purified thyrogobulin prepared from HID and LID rats. No change in susceptibility to digestion of thyroid iodoprotein with time after labeling was seen in hypophysectomized LID rats in which thyroid secretion and thyroglobulin turnover is known to proceed at an extremely slow rate. The data indicate that there are at least two types of iodinated thyroglobulin in the rat thyroid. One is readily susceptible to digestion and has a rapid turnover in the thyroid. The other is more resistant to digestion, has a slow rate of turnover and is located primarily in the peripheral follicles.

Animals↗
PubMed1975

Evidence that the pars intermedia and pars nervosa of the pituitary do not secrete functionally significant quantities of ACTH.

We have compared the capacity to secrete ACTH in response to stress or adrenalectomy in control rats and in those with total hypophysectomy (H), adenohypophysectomy (AH) with preservation of the intermediate and the neural lobes, neurohypophysectomy (NH) with removal of the pars nervosa and all or part of the pars intermedia with preservation of the adenohypophysis, or incomplete adenohypophysectomy (IAH) in which a portion of the adenohypophysis and all of the pars intermedia and pars nervosa were left intact. Plasma ACTH measured with an N-terminal antibody that reacts on an equimolar basis with ACTH and alpha-MSH but not with other known pituitary hormones was elevated after ether or tourniquet stress in all except the H group. Three weeks after adrenalectomy there was an elevated basal plasma ACTH and an augmented ACTH response to stress in intact and IAH but not in AH rats. When a more specific alpha11-24 ACTH antibody was used there was a high plasma ACTH after ether stress in the IAH, NH, and intact groups but not in the AH or H groups. Adrenal weight and plasma corticosterone after tourniquet or ether stress were indistinguishable in the AH and H groups and were much higher and nearly identical in the intact, NH and IAH groups. We conclude that only the adenohypophysis secretes functionally significant amounts of ACTH. Plasma ACTH detected by the N-terminal antibody in the AH group is probably related to alpha-MSH or similar peptides and is incapable of maintaining adrenal weight or stimulating corticosterone secretion.

Adrenal Glands↗
PubMed1975

Changes in plasma thyroxine, triiodothyronine, and TSH during adaptation to iodine deficiency in the rat.

We have measured plasma thyroxine (T4), triiodothyronine (T3), and TSH with specific radioimmunoassays in rats during adaptation to severe iodine deficiency after they had previously received regimens supplying various quantities of iodine. Rats were maintained on a high-iodine diet (HID) containing 3 mg iodine/kg or a low-iodine diet (LID) containing 30 mug iodine/kg supplemented with 0.1, 0.2, or 0.4 mug iodine/ml of drinking water before swtiching to KID alone. Frequent serial blood samples were obtained up to 3 months, using 6 or more animals for each time interval. In animals originally fed HID, T4 remained at 4-6 mug/100 ml unitl the tenth day of LID, then rapidly decreased to a value of less than 0.4 mug/100 ml at 1 month. TSH was initially 50 muU/ml and increased linearly to 165 muU/ml on day 16. Thence there was a much more rapid rate of rise to 640 muU/ml at 38 days. The rats changed to LID alone after having been fed LID with iodine supplementation underwent similar qualitative hormonal changes. However, the decrease in plasma T4 and the increase in plasma TSH occurred sooner in the rats which had drunk water containing only 0.1 or 0.2 mug iodine/ml than in the previous experiment. Rats which had received 0.4 mug iodine/ml showed a pattern essentially identical to that of the animals which had been fed HID. plasma T3 did not change significantly in any of the experiments, remaining at 60-90 ng/100 ml, although there was a tendency for the values to be somewhat lower after several weeks of LID. There was a highly significant negative correlation of plasma T4 with plasma TSH. There was no significant correlation of plasma T3 with either plasma T4 or plasma TSH. It is concluded that the combined physiologic effect of plasma T4 and T3 concentration is more important in determining TSH secretion through negative feedback effects on the hypothalamus and/or pituitary than is the concentration of plasma T3.

Animals↗
PubMed1975

Acute effects of thyroxine, triiodothyronine, and iodide on thyrotropin secretion.

Rats fed a Purina or low-iodine diet (LID) for varying periods were serially sampled before and after a single iv injection of T4, T3, iodide or saline. Suboptimal replacement doses of T4 and T3 were given to rats fed LID for 2 months or 1 year (basal TSH, approximately 1000 and 2000 muU/ml, respectively). Both 1 mug T4 and 0.25 mug T3/100 g BW dropped plasma TSH to 70% of the initial level at 15 min and to 10--20% at 4 h. By 12 h TSH had begun to rise in 2-month LID rats, followed by a secondary decline 3--5 days after injection. Statistical comparison of the slopes of the initial TSH decline indicated there was no significant difference between the effect of T4 and T3. There effect of graded doses of T3 (0.01--0.3 mug/100 g) was also examined. There was a highly significant correlation of the magnitude of TSH suppression with the dose of T3 administered. Saline had no effect but 0.65 mug iodide/100 g BW (equal to that in 1 mug T4) had a delayed effect, depressing TSH to a minimum of 25% of the initial value at 48 h in 2-month LID rats. There was no difference in the effect of these doses of T4, T3, or saline in purina-fed rats (basal TSH, 170 muU/ml). T4 or T3 in physiologically equivalent doses thus produces an identical prompt rate of decrease in plasma TSH, indicating that both hormones possess intrinsic hormonal activity. The delayed effect of iodide is presumably because it must first be incorporated into T4 and T3 and secreted by the thyroid gland. The similarity of depression of plasma TSH by thyroid hormones or saline injection in Purina-fed rats is believed due to a nonspecific stress effect in these animals with a low basal rate of TSH secretion. The non-specific inhibition of TSH secretion is minimal in the iodine-deficient rats with a much higher basal rate of TSH secretion, presumably because of relative vectorial influences.

Animals↗
PubMed1975

Changes in plasma thyrotrophin, thyroxine, and triiodothyronine after acute or chronic administration of iodide to iodine-deficient rats.

The effect of chronic oral or acute iv administration of small graded doses of iodide was studied in severely iodine-deficient rats. Drinking water supplemented with 0.1, 0.2, or 0.4 mug 127I-/ml was given for up to 42 days. Plasma T3, which was initially in the normal range, increased 2--3-fold on days 1 and 2 after initiation of iodide supplementation, then dropped to approximately the intial concentration at day 3. Plasma T4, initially undetectable, was calculated to increase approximately 20-fold within one day after beginning iodide supplementation, but was still climbing into the normal range at day 3. In all groups, the initially high plasma TSH fell significantly by day 1 and was in approximately the normal range for iodine-sufficient rats by day 3. At 42 days, thyroid weight and 131I uptake were significantly elevated in all groups and inversely correlated with the dose of iodide, even though the thyroidal labeled T3/T4 ratio and plasma TSH, T4, and T3 were within the normal range. Intravenous injection of 0.1 or 0.5 mug 125I-/100 g caused an approximately 2-fold increase in plasma T3 within 24 h, which was not statistically different between the 2 groups. Plasma T4 rose to the normal range 24 h after 0.5 mug and was slightly, but significantly, elevated after 0.1 mug; it then declined in both groups. Twenty-four hours after injection of 2.5 mug 125I-/100 g, there was a significant fall in plasma T3, no change in plasma TSH, and no detectable plasma T4. Thereafter, there was a dramatic increase in plasma T4 and a fall in plasma TSH. The duration and degree of suppression of plasma TSH was related to the dose of iodide injected. We conclude that, under the conditions of our experiments, plasma T3 derives primarily from thyroidal secretion rather than from extra-thyroidal conversion of T4 to T3. Severely iodine-deficient rats secrete maximum quantities of TSH which are not increased by a further transient drop in plasma thyroid hormone concentration.

Administration, Oral↗
PubMed1975

A sensitive and simple in vitro assay for corticotropin-releasing substances utilizing ACTH release from cultured anterior pituitary cells.

Graded doses of rat hypothalamic extract (HE) were added to dishes containing dispersed, pooled rat adenohypophyseal cells cultured for several days. ACTH secretion into the medium gave a linear log-dose response curve over a 100-fold range between 0.01 and 1 mg of NIH-HE (0.0125-1.25 rat hypothalamus). Forty percent of the maximal ACTH secretion in response to a given dose of HE occurred within 3 min. No decrease in intracellular ACTH occurred at any time or with any dose of HE, indicating that secretion was always balanced by production. ACTH secretion stopped as soon as HE-containing medium was replaced by medium without HE. The same cultured cells could be satisfactorily used in repetitive assays performed on the same or different days.

Adrenocorticotropic Hormone↗
PubMed1975

Nyctohemeral and sex-related variations in plasma thyrotropin, thyroxine and triiodothyronine.

TSH, T4, and T3 were measured by radioimmunoassay in plasma samples obtained from 77 young adult male and 114 female rats fed a Purina high-iodine diet and maintained in an isolated room, 2-4/cage, at 24 +/- 1 C with light from 0600-1800 h. In one experiment, 7 male and 7 female rats were decapitated every 3 h for 30 consecutive h and trunk blood was collected. There was a clear nyctohemeral rhythm of plasma TSH in both sexes characterized by a zenith at 1200 h and a nadir between 1800 and 2100 h. The plasma TSH cycle was approximately 180 degrees out of phase and negatively correlated (P less than .05) with that of plasma corticosterone (B) in both sexes. Although glucocorticoids have been reported to suppress TSH secretion, there was no causal relationship between plasma B and TSH in our experiments since the TSH cycles were normal in chronically adrenalectomized rats. Normal TSH cyclicity was not observed in severely iodine-deficient rats with extremely high plasma TSH levels although the nyctohemeral B rhythm was normal. Plasma TSH was approximately twice as high in males as in females (overall mean +/- SE: M = 149 +/- 11, F = 81 +/- 7 muU/ml, p less than 0.001). There was no significant difference (P greater than 0.05) in plasma TSH at different stages of the estrous cycle. Plasma T4 was slightly, but significantly, higher in males than females (overall mean +/- SE: M = 6.4 +/- 0.1, F = 6.0 +/- 0.1 mug/100 ml; P less than 0.001), while T3 was higher in females than in males (overall mean +/- SE: M = 69.5 +/- 1.7, F = 80.3 +/- 2.1 ng/100 ml; P less than 0.001). No significant nyctohemeral rhythm was observed in plasma T4 or T3 in either sex. These observations indicate that: 1) There is a nyctohemeral rhythm of plasma TSH which is independent of plasma B fluctuations and not associated with proportional changes in plasma thyroid hormones. 2) A sustained high rate of TSH secretion abolishes the normal nyctohemeral plasma TSH rhythm. 3) There are significant differences in plasma concentrations of TSH, T4, and T3 between male and female rats.

Adrenal Glands↗
PubMed1975

The relative roles of iodination and iodothyronine content on thyroglobulin stability.

We have independently varied the degree of iodination and of iodothyronine formation over a wide range by acutely administering various doses of perchlorate and/or methimazole to severely iodine-deficient rats 30 min before giving 131-I- with graded quantities (1-100 mug of 127-I-). Thyroids were removed 4 h later and the soluble protein analyzed for labelled iodoamino acid composition and with sucrose density gradient ultracentrifugation. Since the total thyroid iodine content before administering 127I- was less than 1 mug, calculation of the degree of iodination and iodothyronine content of the labelled Tgb could be made from the known specificity of the injected labelled iodide. Newly organified iodine ranged from smaller than 0.1 to 1.4 mug/thyroid and labelled iodothyronines from smaller than 5 to 962 pmoles/thyroid. Both the degree of iodination and iodothyronine content varied directly with Tgb stability in the absence of inhibitors. But when Tgb iodination was kept constant, Tgb stability at pH 10.1 varied directly with iodothyronine content. When iodothyronine content was kept constant, Tgb stability was independent of the degree of iodination. Correlation of stability with iodothyronine content was highly significant (r=0.79, Psmaller than 0.001) but not of stability with iodine content (r=0.49, P larger than 0.05). We conclude that the primary determinant of Tgb stability in mild alkali is the iodothyronine content and not the degree of iodination of the protein. The increased Tgb stability may be induced by coupling between iodotyrosil residues of different 12 S subunits rather than between residues of the same 12 S subunit.

Animals↗
PubMed1975

Absence of nyctohemeral variation in stress-induced ACTH secretion in the rat.

Changes in plasma ACTH concentrations were measured in the adult male rat following a stressor in order to ascertain if there is a nyctohemeral variation in ACTH secretion following stress. The immuno-reactive ACTH concentrations obtained following a 2.5-min hind-leg tourniquet at 0400 or 1600 hours in pentobarbital-anesthetized animals were compared to those obtained in anesthetized and unanesthetized, unstressed controls. Neither absolute nor increment change in plasma ACTH concentrations following morning or afternoon tourniquet stress were significantly different after either 20 or 40 min anesthesia. Moreover, plasma ACTH concentrations from unstressed, unanesthetized rats showed a slight but significant difference (p smaller than 0.05) at 0400 hours [118 plus or minus 18 pg/ml (mean plus or minus SE)] compared to 1600 hours (64 plus or minus 12 pg/ml) indicating a reversal of the expected ACTH rhythm. Plasma corticosterone concentrations in these same rats showed the predicted lower-morning and higher-afternoon corticosterone pattern suggesting a possible nyctohemeral difference in the adrenal sensitivity to circulating levels of ACTH.

Adrenocorticotropic Hormone↗