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Biomedical subjects

J Golstein

Publications and source records attributed to J Golstein.

At least 37 records · Page 2Linked to original sources

24-hour profiles of adrenocorticotropin, cortisol, and growth hormone in major depressive illness: effect of antidepressant treatment.

Plasma ACTH, cortisol, and GH concentrations were measured at 15-min intervals for 24 h in 11 men suffering from major depressive illness during an acute episode of depression and during clinical remission following antidepressant treatment with either electroconvulsive therapy or amitriptyline. Seven age-matched normal men also were studied. During the acute phase of the illness, the patients had abnormally short rapid eye movement sleep latencies, hypercortisolism, early timing of the nadirs of the ACTH-cortisol rhythms, and shorter nocturnal periods of quiescent cortisol secretion. GH was hypersecreted during wakefulness, and a major pulse occurred before, rather than after, sleep onset. After treatment, rapid eye movement sleep latencies were lengthened, and cortisol levels returned to normal due to a decrease in the magnitude of episodic pulses. Moreover, the timing of the circadian rhythms of ACTH and cortisol as well as the duration of the quiescent period of cortisol secretion were normalized. The amount of GH secreted during wakefulness decreased to normal values, with fewer significant GH pulses. The major elevation of GH secretion in the early part of the night occurred later than that during the depressive episode. These results demonstrate that a disorder of circadian rhythmicity characterizes acute episodes of major depressive illness and that this chronobiological abnormality as well as the hypersecretion of ACTH, cortisol, and GH are state rather than trait dependent.

Adrenocorticotropic Hormone↗

Selenium deficiency as a possible factor in the pathogenesis of myxoedematous endemic cretinism.

Myxoedematous endemic cretinism is prevalent in African goitre endemies. It has been related to a thyroid 'exhaustion' atrophy occurring near birth. It is proposed that this might result from the low resistance of a fragile tissue to enhanced H2O2 generation under intense thyroid stimulation by thyrotropin. In support of this hypothesis, low selenium and glutathione peroxidase serum levels have been found in the African endemic area of the Idjwi Island (Kivu, Zaire). Serum selenium and plasma glutathione peroxidase were lower in the area of high endemicity of goitre and cretinism (Northern part of the Island). However, only the former difference is statistically significant. These data thus suggest a role of oligoelements and oxygen toxicity in the pathogenesis of endemic cretinism.

Adolescent↗

Cell kinetics of thyroid epithelial cells during hyperplastic goitre involution.

Thyroid epithelial cell kinetics were investigated in rats when a normal iodine diet was re-established after a long period of iodine deficiency supplemented with propylthiouracil (0.15%) for the last 2 months. In the first (prelabelling) experiment, all rats were labelled with a single injection of [3H]thymidine 2 days before iodine refeeding in order to follow the fate of the prelabelled cells. In the second experiment, the pulse-labelling index at the time of killing was measured; for this purpose the rats received [3H]thymidine 1 h before death. In these two experiments autoradiography was performed on histological sections. Thyroids were excised on day 0 and then at various intervals up to day 73 of iodine refeeding. Plasma tri-iodothyronine (T3) and thyroxine (T4) were very low until day 4 and then increased to reach control values on day 30. Thyroid concentration of iodide rose to 20 times the value on day 0, remained at this high level until day 2, and then diminished on day 4 to reach the control value on day 16. Plasma TSH concentrations were very high in iodine-deficient rats and did not vary significantly until day 8, when they fell rapidly to reach the control value on day 30. Thyroid weight, raised on day 0, decreased relatively quickly until day 4, then more slowly until day 30. Total thyroid epithelial cell number, high on day 0 (30.7 x 10(6) cells) was constant until day 16, then decreased until day 30 at which time a plateau was reached.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Negative effect of iodide on the survival of newly divided epithelial cells in chronically stimulated rat thyroid.

The aim of this work was to investigate some aspects of the thyroid epithelial cell kinetics during the iodide-induced involution of a hyperplastic goitre in the rat. Rats were made iodine-deficient for 6 months, and propylthiouracil (PTU) (0.15%) was added to the diet during the last 2 months. Thereafter, rats were refed with iodide and PTU was removed (day 0). Forty-eight hours previously, all the rats were injected with tritiated thymidine ([3H]TdR) (1 microCi/g). Some animals were killed 1 hr or 24 hr after [3H]TdR injection (i.e. on day -2 and -1, day 0 corresponding to the restoration of a normal iodine diet); the other animals were killed after different delay periods and following [3H]TdR injection. Autoradiography of thyroid sections, iodine determination of plasma iodide and protein-bound iodine (PBI), and RIA of plasma thyroid stimulatory hormone (TSH) were performed. Plasma TSH concentration was very high on day 0 of iodide refeeding (3000 +/- 330 ng/ml) and remained at this level until day 8. Plasma PBI was very low on day 0, remained so until day 4 and greatly increased on day 8. Plasma iodide was also very low on day 0, but markedly increased on day 1, then did not vary significantly until day 43 of iodine refeeding. Thyroid weight, elevated on day 0, decreased relatively quickly until day 30, then more slowly until day 73. The [3H]TdR labelling index (LI) of the thyroid epithelial cells (TEC) was high on day 0 (56 +/- 3 labelled cells/10,000 cells), and 24 hr thereafter increased to 104 +/- 3, by division of the labelled cells. On day 1 of iodine refeeding, the LI had abruptly decreased to about half this value and then remained stable for 3 more days. Between day 4 and day 16, a progressive decline in the LI, (by about 3-4 per day), was observed. The LI showed no further modification, up to day 73, the longest period investigated. The decrease in LI occurred without any significant changes in the labelling intensity (grain count) of the remaining labelled cells between day 1 and 16, this indicates that no cell division took place during this period. The data are therefore interpreted as showing a biphasic elimination after iodide refeeding, of cells that were actively proliferating during the goitrous state.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Prolonged pulsatile administration of ovine corticotropin-releasing hormone in normal man.

The 24-h profiles of plasma ACTH and cortisol were determined at 15-min intervals in five normal men basally and during iv bolus injections of 25 micrograms ovine corticotropin-releasing hormone (oCRH) every 4 h for 72 h. Each oCRH injection was followed by a distinct elevation of plasma ACTH and cortisol levels, with a return to basal values before the next injection. The characteristics of the ACTH and cortisol pulses induced by 25 micrograms oCRH (i.e. 0.3-0.4 micrograms/kg) were similar to those observed in other studies with 1 microgram/kg human CRH. There was no significant blunting of oCRH-induced hormonal increments in the course of the 72-h study. On each oCRH injection day, the mean 24-h cortisol level was higher than that in the basal study, but there was no increase in the mean 24-h ACTH level. During the 72-h oCRH study, the preinjection ACTH and cortisol levels exhibited a diurnal variation, indicating persistence of the circadian periodicity of pituitary-adrenal activity. There was a diurnal variation of oCRH-induced ACTH increments, with highest responses at 0700 h. A small but not significant reverse trend was apparent for cortisol increments. Spontaneous pulses of ACTH and cortisol occurred throughout the 3 days of oCRH injections, and the total number of spontaneous and oCRH-induced pulses was similar to the number of spontaneous pulses observed in the basal study. All oCRH-induced and more than 90% of spontaneous cortisol pulses occurred concomitantly with an ACTH pulse. The variability of pulse increments was greater for ACTH than for cortisol. In conclusion, prolonged pulsatile administration of oCRH did not induce pituitary desensitization and did not suppress the endogenous circadian and pulsatile ACTH and cortisol variations.

Adrenocorticotropic Hormone↗

Modulation of immunoreactive somatomedin-C levels by sex steroids.

Among 28 menstruating women tested once randomly during the cycle, somatomedin-C (Sm-C) values were lower in the 10 women in normal follicular phase than in the 10 women in normal luteal phase or the 8 women with hyperandrogenism. Among these 28 subjects, Sm-C showed a positive correlation with testosterone and a positive correlation of borderline significance with oestradiol. A positive correlation was also evidenced between Sm-C and in progesterone among the 20 women of this group who were not hyperandrogenic. In 5 other normal women investigated daily throughout an entire menstrual cycle, Sm-C concentrations were higher during days +4 to +9 of this cycle (luteal phase) than during days -3 to -8 (follicular phase). In another group of 21 healthy women, Sm-C values were increased during medroxyprogesterone acetate (150 mg trimestrially) treatment. In 7 normal men, Sm-C decreased during ethinyl-oestradiol (1 mg daily for 5 days) administration. These findings suggest that circulating Sm-C levels are modulated by variations of sex steroids which occur during the menstrual cycle as well as by pharmacological doses of oestrogens and progestagens.

Adult↗

Relationship between serum thyroglobulin and intrathyroidal stable iodine in human simple goitre.

Serum thyroglobulin levels are increased in many patients with simple goitre. This increase has been attributed to the release of thyroglobulin (Tg) from the colloid of necrosed follicles. To test the hypothesis that increased serum Tg could be related to the low intrathyroidal iodine concentration [I], the main cause of nontoxic goitre, these two variables were measured in 91 euthyroid goitrous patients and compared to serum free T3 and free T4 levels as well as thyroid weight. Thyroid iodine concentration was estimated from the X-ray fluorescence measurement of intrathyroidal iodine stores and from the weight of the gland estimated by planimetry. Serum Tg levels, the free T3/T4 ratio and thyroid weight were negatively correlated to [I] (Spearman's coefficient of correlation = - 0.44 (P = 0.001); -0.30 (P = 0.006); -0.33 (P = 0.001), respectively). Tg levels were also positively correlated to the T3/T4 ratio (R = 0.28, P = 0.008) and to the weight of the gland (R = 0.37; P = 0.001). These data suggest that, in simple goitre, increased serum Tg concentrations are partly related to the reduced concentration of iodine in goitre tissue (as are an increased T3/T4 ratio and the size of the goitre) and is not only the reflection of follicular necrosis.

Goiter↗

Diurnal hypersecretion of growth hormone in depression.

A 24-h profile of plasma GH concentrations was obtained together with polygraphic recordings of sleep in 16 men suffering from a major depressive disorder (8 unipolar and 8 bipolar) and in 8 age- and sex-matched normal men. None of the patients had any physical illness. All were studied after a drug-free period of at least 15 days. Blood was sampled every 15 min. The amount of GH released in every significant secretory spike was estimated using a computer program. Both unipolar and bipolar depressed patients secreted more GH than normal men (mean +/- SD, 441 +/- 189 micrograms/24 h for unipolar depressed men; 357 +/- 143 micrograms/24 h for bipolar depressed men vs. 172 +/- 101 micrograms/24 h for normal men (P less than 0.01). This hypersecretion occurred during waking hours rather than during sleep. The increase in daytime GH release was more marked in unipolar depressed patients. During sleep, depressed patients and normal men secreted similar amounts of GH despite an overall reduction in slow wave stages in depressed patients. An early sleep GH increase was found in all but one of the normal men, but was absent in seven of the eight unipolar depressed patients, who had, instead, a presleep increase in between 2100-0000 h. No consistent disturbance of the temporal association between sleep onset and GH secretion was found in bipolar depressed patients.

Adult↗

The 24-hour profile of adrenocorticotropin and cortisol in major depressive illness.

The 24-h profile of plasma ACTH and cortisol levels was determined in 18 men suffering from major depressive illness (8 with unipolar depression and 10 with bipolar depression) as well as in 7 age-matched normal men. Blood was sampled every 15 min. The circadian variation and episodic fluctuations were analyzed for each individual profile. Both unipolar and bipolar depressed patients had higher 24-h mean cortisol levels (P less than 0.01) than normal men, but no significant difference in 24-h mean ACTH level was found. The nadir of cortisol secretion occurred almost 3 h earlier in older normal subjects and patients with unipolar depression, regardless of age, than in younger normal subjects. This shift paralleled a similar advance of the ACTH nadir. Early timing of the quiescent period of ACTH-cortisol secretion was also found in several patients with bipolar depression, but did not reach significance at the group level. The hypercortisolism in the depressed patients was associated with an increase in the magnitude, but not the number, of cortisol secretory episodes. About 90% of the cortisol pulses could be related to a concomitant ACTH pulse in normal subjects as well as in both groups of depressed patients. However, concomitant ACTH and cortisol pulses were less correlated in magnitude in depressed patients than in normal subjects. These results indicate that major depressive illness is associated with disturbances of pituitary-adrenal function. The early timing of the nadir of ACTH-cortisol secretion suggests that disorders of circadian time keeping may characterize major endogenous depression.

Adrenocorticotropic Hormone↗

[Possible regulation of the growth of thyroid tissue by plasma iodide].

Rats on iodine deficient diet for 6 months received propylthiouracil (PTU) (0.15%) during the last 2 months. At the end of this treatment, PTU was withdrawn and the rats were iodine refed. 48 hrs. before the iodine refeeding all rats were injected with 3H thymidine. The results showed that some prelabelled cells in the hyperplastic goitre preferentially disappeared during its involution and therefore are more sensitive to iodine.

Animals↗

Relations between immunoreactive somatomedin C, insulin and T3 patterns during fasting in obese subjects.

Plasma glucose, immunoreactive somatomedin-C (Sm-C), GH, insulin (IRI) and T3 were measured daily in 20 obese subjects before and during a 9-day fast. Control levels of Sm-C were normal and exhibited no significant correlation with any of the other parameters investigated. During fasting there were no consistent variations in GH, but significant decreases occurred in blood glucose, IRI, T3 and Sm-C levels. While individual Sm-C patterns varied widely, as a group the fasting Sm-C values showed a positive correlation with the fasting IRI and T3 levels, and with control body weight. These findings suggest that the decrease in Sm-C which occurs during caloric deprivation may be the result of concomitant decreases occurring in T3 and IRI levels.

Adolescent↗

Thyroid lysosomal enzyme activity and ultrastructure after subtotal thyroidectomy.

Subtotal thyroidectomies were performed in rats to increase the level of endogenous TSH, creating a condition of chronic TSH stimulation. The activities of various classes of lysosomal enzymes (cathepsin D, beta-glucuronidase, and aryl sulfatase A) were studied in thyroid tissue remaining in situ at various time intervals after subtotal thyroidectomy (sub-tx). These alterations were correlated with morphometric and ultrastructural changes in tissue lysosomes and with serum T4 and TSH. Specific activities of all three lysosomal enzymes were elevated in the residual tissue as compared with those in control tissue during 7 weeks after sub-tx in the first experiment. In the second experiment, the activities of all three enzymes were elevated both 3 and 6 weeks after sub-tx, and the activities of cathepsin D and aryl sulfatase A in the postnuclear homogenate (S2) were significantly elevated. Plasma TSH was elevated and T4 was decreased both 3 and 6 weeks after sub-tx. The results of the third experiment determined that there were significant alterations in nuclear cytoplasmic ratios as well as in the number, area, and volume density of lysosomes in both groups compared with respective control values. In addition, both lysosomal area and volume density in animals 6 weeks after sub-tx were significantly larger than those in animals 3 weeks after sub-tx. We conclude that chronic stimulation of residual thyroid tissue 6 weeks after sub-tx causes alterations in lysosomal ultrastructure as well as in lysosomal enzyme activity.

Animals↗

Effect of fluoxetine, a serotonin reuptake inhibitor, on the pituitary-thyroid axis in rat.

Fluoxetine, a specific serotonin reuptake inhibitor, was administered i.p. either acutely or chronically (2 and 10 mg doses), and intraventricularly to normal rats. Basal TSH levels were measured and the pituitary TSH reserve was estimated by direct determination of pituitary TSH content and/or by a TRH test. Thyroxine (T4) and triiodothyronine (T3) serum levels were also measured. The acute administration elicited only a decrease in T4 levels, whereas the chronic administration resulted in a decrease in both T4 and T3 levels. The 10 mg acute and chronic administrations induced an increase in basal TSH and in pituitary TSH reserve. Intraventricular administration only prevented the initial stress-induced decline of serum TSH levels. The major effect of the drug seems to be stimulation of TSH synthesis and release via the inhibition of T4-mediated thyroid-pituitary feedback. Additionally, fluoxetine could exert a minor direct central stimulatory effect on TSH secretion.

Animals↗

Ultrastructural and functional effects of chronic endogenous stimulation of thyroid cells by thyrotropin.

Following total thyroidectomy, a small quantity of thyroid tissue was transplanted to the spleen in order to study thyroid tissue subjected to chronically elevated levels of endogenous thyrotropin (TSH). Plasma thyroxine (T4) and TSH levels were monitored and correlated with ultrastructural studies of the tissue over a 32-week experimental period. The effects of administration of an iodine-poor diet, and exogenous acute dose of TSH, and suppression of endogenous TSH through thyroxine administration were studied in order to evaluate the plasticity of the experimental model. Plasma T4 decreased after the first week and remained at approximately one half of the initial value until 12 weeks. Plasma TSH increased to a high of 6,220 ng/ ml after 6 weeks and gradually declined to one half of that value. The transplanted tissue remained functional throughout the experimental period. The number of pseudopods decreased, and irregularly shaped, dense bodies increased from the time of surgery until 12 weeks later. Administration of an acute dose of TSH at this time resulted in obvious mitotic activity and the formation of numerous pseudopods. The tissue also maintained the ability to take up radioactive iodine and to iodinate thyroglobulin. Inhibition of TSH secretion through T4 administration from the time of surgery did not affect viability. Some cellular hypertrophy persisted after 32 weeks although TSH and T4 had returned to normal. This study has shown that thyroid tissue remains viable, functional, and experimentally alterable throughout an extended period of chronic stimulation by endogenous TSH, and that it has the reserve capacity to secrete normal levels of T4 at the end of this experimental period.

Animals↗

Thyroidal release after oral administration of TRH in normal subjects.

The oral administration of 40 mg TRH to 17 normal volunteers induced a greater TSH response in females than in males, contrasting with an identical pattern of total T3 and T4 (TT3, TT4) and of free T3 and T4 (FT3, FT4). TSH peaked at 180 min while thyroid hormones (total and free) reached their maximum at 360 min. The drop in the T4 to T3 ratio (total and free hormones) observed at 360 min is consistent with an initial preferential T3 secretion. At 360 min the thyroglobulin (Tg) levels were still in the basal range while at 24 h a significant increase was observed, essentially in female subjects. Thus T3, T4 and Tg seem to be sequentially secreted by the thyroid in response to a prolonged TSH stimulus.

Administration, Oral↗