Biomedical subjects

T Lemarchand-Beraud

Publications and source records attributed to T Lemarchand-Beraud.

15 recordsLinked to original sources

PubMed1995

Severe but not mild alterations of thyroid function modulate the density of thyroid-stimulating hormone receptors in the rat thyroid gland.

TSH initiates its action by binding to specific membrane receptors' thyroid cells and induces activation of the adenylate cyclase-cAMP cascade. The factors involved in the regulation of TSH receptors are poorly known, except for the TSH dose-dependent regulatory effect. The fact that the thyroid gland of Graves' patients has a normal density of TSH receptors with suppressed TSH and high T4 and T3 levels suggests a modulatory role of thyroid hormones on TSH receptors. To evaluate this hypothesis, the density of TSH receptors and the activity of adenylate cyclase were determined in the thyroid membranes from hyperthyroid and hypothyroid adult male rats; they were rendered hyperthyroid either with bovine TSH, TRH, or T3 for 7 days and hypothyroid by propylthiouracil treatment or by hypophysectomy. NaCl was given to the control group. Plasma T4, T3, and TSH were also quantified. Bovine TSH and TRH treatments induced mild hyperthyroidism with a small goiter and a 50% reduction in the density of TSH receptors due to hyperstimulation of the gland by either exogenous or endogenous high TSH levels. Severe hyperthyroidism caused by T3 treatment resulted in low T4, high T3, and suppressed TSH thyrocyte stimulation; it was associated with a significant increase in the number of TSH receptors (29.6 +/- 2.3 vs. control 17.9 +/- 1.7 mU TSH/mg protein). These last results suggest a putative positive effect of T3 on TSH receptors. To confirm this effect, hypothyroid rats were investigated. Severe primary hypothyroidism due to propylthiouracil treatment was associated with a large goiter, high plasma TSH levels (11.8 +/- 1.2 vs. control 1.5 +/- 0.1 mU TSH/ml), low plasma T4 and T3, and a 70% reduction in TSH receptors, confirming the down-regulatory effect of high TSH on the thyroid cell. However, in hypophysectomized rats, a 45% reduction in the density of TSH receptors was also observed in the absence of TSH. Injections of either TSH or T3 to these hypophysectomized rats restored a normal number of TSH-binding sites, and simultaneous TSH and T3 treatments resulted in a mildly additive effect in the number of TSH receptors, which was slightly greater than that of the controls. No important changes were found in the adenylate cyclase activity in the thyroid membrane preparations from hyperthyroid and hypothyroid rats despite variations in the density of TSH receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗

PubMed1994

Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin.

Some years ago, we reported that colloid goiters could be produced experimentally in mice and rats by injection of TSH over a few days in the presence of ample iodine supply. This clearly showed that colloid accumulation and intense TSH stimulation are not mutually exclusive. In the present study, large colloid goiters, sharing many morphological and biochemical characteristics with human colloid goiters, were induced in rats and mice by treatment with 5,5-diphenyl-2-thiohydantoin (DPTH). This drug increases fecal loss of thyroid hormone and inhibits conversion of T4 to T3. Thus, DPTH raises TSH and induces macrofollicular colloid-rich goiters. In contrast to this, goiters induced by combined treatment with methimazole (MMI) or sodium perchlorate and DPTH are microfollicular, although serum TSH is increased to the same level as in rats treated with DPTH alone. The degree of iodine organification obviously determines if the follicle will sprout and form daughter follicles or if it will expand its hull. Thyroglobulin content of DPTH goiters is lower than that of normal glands but considerably higher than after MMI treatment, whereas total iodine content of DPTH goiters is only slightly lower than in normal glands, but also much higher than in MMI goiters. In DPTH goiters, a high proportion of total iodine is in the particulate fraction which probably contains the periodic acid Schiff-positive bodies floating in the colloid of DPTH treated glands. Acute DPTH administration does not inhibit iodide organification, but after treatment with DPTH for 1 day, chromatography suggests some inhibition of iodine organification and hormone synthesis by DPTH, but much less than by MMI. DPTH treatment causes considerable tissue damage and repair, such as follicular cell necrosis and invasion of the colloid by macrophages and granulation tissue. Therefore, DPTH goiters might well be a useful model not only for colloid goiter formation but also for inflammatory processes in the thyroid gland.

Animals↗

PubMed1989

Down regulation of hypertrophied follicular cell volume in thyroid hyperplastic gland.

In the present study, changes in thyroid follicular cell volume and its regulation have been investigated during the early involution of a hyperplastic goitre. Male Wistar rats were administered an iodine deficient diet for 6 months with propylthiouracil (PTU, 0.15%) during the last two months. At the end of iodine deficiency (day 0), some rats were killed and the others received a normal iodine diet. These rats were killed after different periods of iodine refeeding. Thyroid follicular cell volume was very high in hyperplastic gland whereas thyroid protein concentration was low. Thyroid follicular cell volume quickly decreased when rats were normally iodine refed, whereas thyroid protein concentration increased. Electron microscopal observations showed that thyroid follicular cells retained their endocrine aspect in hyperplastic state and throughout the iodine refeeding period. Using concomitant stereological and biochemical techniques, it is shown that the amount of cellular iodide and an unknown iodinated compound strongly increased during the early iodine refeeding. Plasma TSH was high on day 0 and remained at this level until day 8 whereas plasma T3 and T4 were low on day 0 and remained at this low level until day 4. The present data show that the involution of thyroid follicular cell volume is induced by iodide and mediated by an iodinated compound at least in the initial phase, and is independent of plasma TSH, T3, T4, so indicating the involvement of a thyroid autoregulatory mechanism. These changes in cell volume may be of importance in ion transport, i.e. in the metabolism of thyroid follicular cell during the early involution of the hyperplastic goitre.

Animals↗

PubMed1986

Effect of oral triiodothyronine during amiodarone treatment for ventricular premature complexes.

Whether there is a link between the antiarrhythmic efficacy of amiodarone and its blocking effect on the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) is uncertain. If such a link exists, oral intake of T3 during amiodarone treatment could reverse, at least partially, the antiarrhythmic efficacy of amiodarone. To assess the safety of oral intake of T3 during amiodarone treatment and gain further insight into the relation between the antiarrhythmic action of amiodarone and its metabolic effect on T4, 7 patients (aged 32 to 62 years) with multiple ventricular premature complexes (VPCs) but no underlying heart disease were studied. Antiarrhythmic treatment was indicated for symptomatic relief only. Each patient underwent a 48-hour ambulatory electrocardiographic recording, electrocardiography and thyroid function tests, including plasma T4, T3, reverse T3 (rT3), free T4, free T3 and thyroid-stimulating hormone without treatment (baseline) after 1 month of amiodarone therapy and after a second month of amiodarone therapy with increasing doses of oral T3 (up to 75 micrograms/day). Treatment with amiodarone resulted in a decrease in plasma T3 and free T3, an increase in plasma rT3, a marked diminution in the frequency of VPCs and a prolongation of the corrected QT interval (QTc). During treatment with amiodarone and T3, plasma T3 and free T3 increased and plasma T4, free T4 and rT3 levels decreased; the frequency of VPCs remained low despite shortening of the QTc to values not different from baseline. Thus, in patients with frequent VPCs and no underlying heart disease, oral intake of T3 during amiodarone treatment is safe and does not abolish the antiarrhythmic efficacy of amiodarone, despite a shortening of the QTc.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1985

[Effect of cycloheximide on nuclear triiodothyronine receptors in the pituitary of the normal and hypothyroid rat].

Cycloheximide (Cy), an inhibitor of protein synthesis was found to provoke a dose-dependent decrease of the hypophysis T3 nuclear receptors (T3nR) concentration in normal rats. In thyroidectomized rats, the reduced T3nR density was found to be normalized within 3 hrs. after a single injection of T3. Pretreatment with Cy inhibited the T3 effect on its own receptors, whereas Cy given after T3 was partially or not effective. These data suggest that the half-life of T3nR in the hypophysis is short (about 3 hrs.), and that it depends on protein neosynthesis.

Animals↗

PubMed1983

Effects of hyper- and hypoprolactinemia on gonadotropin secretion, rat testicular luteinizing hormone/human chorionic gonadotropin receptors and testosterone production by isolated Leydig cells.

The effect of prolactin (Prl) on gonadotropin secretion, testicular luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors, and testosterone (T) production by isolated Leydig cells has been studied in 60-day-old rats treated for 4 days, 4 and 8 weeks with sulpiride (SLP), a dopaminergic antagonist, or for 4 days and 4 weeks with bromocriptine (CB), a dopaminergic agonist. Plasma Prl concentrations were significantly greater in the SLP groups (204 +/- 6 ng/ml) and lower in the CB groups (3.0 +/- 0.2 ng/ml) than those measured in the control groups (54 +/- 6 ng/ml). The plasma concentrations of gonadotropin were not affected by a 4-day treatment with SLP or CB, nor were they after a 4-week treatment with CB. However, the hyperprolactinemia induced by an 8-week treatment with SLP was associated with a reduced secretion of gonadotropin (LH, 16 +/- 4 vs. 35 +/- 6 ng/ml; FSH, 166 +/- 12 vs. 307 +/- 14 ng/ml). In SLP-induced hyperprolactinemia, a 30% increase in the density of the LH/hCG testicular binding sites was observed (178 +/- 12 fmol/mg protein), whereas a 60% decrease was measured in hypoprolactinemia (55 +/- 5 vs. control 133 +/- 5 fmol/mg protein). Plasma T levels were increased in 4-day and 4-week hyperprolactinemic animals (4.3 +/- 0.4 and 3.9 +/- 0.4 ng/ml, respectively), but returned to normal levels in the 8-week group (3.0 +/- 0.5 vs. C: 2.3 +/- 0.2 ng/ml). No T modifications were observed in hypoprolactinemic animals. Two distinct populations of Leydig cells (I and II) were obtained by centrifugation of dispersed testicular cells on a 0-45% continuous Metrizamide gradient. Both possess LH/hCG binding sites. However, the T production from Leydig cells of population II increased in the presence of hCG, whereas that of cell population I which also contain immature germinal cells did not respond. The basal and stimulated T secretions from cell populations I and II obtained from CB-treated animals were similar to controls, whereas from 4 days to 8 weeks of hyperprolactinemia, basal and hCG induced T productions from cell population II decreased progressively. These data show that hyperprolactinemia causes, in a time-dependent manner, a trophic effect on the density of LH/hCG testicular receptors; reduces basal and hCG-stimulated T production from isolated Leydig cells type II; and results in an elevated plasma T concentration which decreases with time. The latter suggests a slower T catabolism and/or an impaired peripheral conversion of T into 5 alpha-dihydrotestosterone (DHT). Although hypoprolactinemia is associated with a marked reduction in testicular LH receptors, it does not affect T production.

Animals↗

PubMed1982