Biomedical subjects

G Cabello

Publications and source records attributed to G Cabello.

At least 37 records · Page 2Linked to original sources

PubMed1995

Stimulation of avian myoblast differentiation by triiodothyronine: possible involvement of the cAMP pathway.

In a previous work, we have shown that T3 induces a potent stimulation of avian myoblast differentiation. In this study, we demonstrated that this hormone did not affect MyoD and myogenin expression. As numerous data suggest that T3 could affect the cAMP pathway, we have studied its involvement in the myogenic activity of triiodothyronine on quail myoblast. In agreement with Zalin and Montagues (Cell 2, 103-108 (1974)), we observed a transient rise in myoblast intracellular cAMP level some hours before the onset of terminal differentiation. Interestingly, this rise occurred earlier in T3-treated than in control myoblasts, and cAMP production was significantly increased by the hormone. Moreover, T3 increased CREB transcriptional activity, thus suggesting that the entire cAMP signaling pathway was stimulated by this hormone. In addition, we observed that addition of an inhibitor of adenylate cyclase activity prior to the cAMP rise dramatically inhibited myoblast differentiation. Last, we showed that cAMP mimicked all T3 actions upon myoblast differentiation: (1) T3 and cAMP reduced myoblast proliferation by increasing the number of postmitotic myoblasts at cell confluence; (2) T3 and cAMP increased BTG1 nuclear accumulation; (3) T3 and cAMP stimulated terminal differentiation only when added during the proliferative phasis. These data strongly suggest that the transient rise in cAMP production could be essential for myoblast terminal differentiation. In addition, it appears that, at least in avian myoblasts, T3 stimulation of terminal differentiation involves the cAMP pathway.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1995

Cardiovascular responses to graded degrees of hypoxaemia in the llama fetus.

The fetal llama exposed to an intense degree of hypoxaemia did not increase cerebral blood flow, but showed a marked peripheral vasoconstriction. The same cardiovascular response is observed in fetal sheep submitted to a extremely severe hypoxaemia, when the initial compensatory vasodilatory mechanisms in brain and heart fail. To investigate whether the fetal llama responses to acute hypoxaemia are adaptive, or whether they are the result of a breakdown of mechanisms of blood flow redistribution that favours the central nervous system, we studied seven fetal llamas (0.6-0.7 of gestation) chronically-catheterized during 1 h of graded and progressive hypoxaemia. Fetal ascending aorta blood gases and fetal cardiac output and its distribution (radiolabelled-microspheres) were measured after 60 min of normoxaemia (B) and at the end of 20 min (H20), 40 min (H40) and 60 min (H60) of hypoxaemia. Data were analysed by ANOVA and Newman-Keuls tests. Each treatment resulted in a lower (P < 0.05) percentage of haemoglobin saturation than hypoxaemia; H40 was lower than H20, and H60 was lower than H20 and H40. No statistical difference was observed among treatments for cardiac output or cerebral blood flow. These results demonstrate that fetal cardiac output and brain blood flow are maintained at all degrees of hypoxaemia, indicating that these cardiovascular responses are an adaptive response in the llama fetus, rather than an index of cardiorespiratory decompensation.

Animals↗

PubMed1994

v-erbA stimulates quail myoblast differentiation in a T3 independent, cell-specific manner.

The v-erbA oncoprotein represents a mutated version of a thyroid hormone receptor, responsible for the induction of a differentiation arrest in chicken erythroid cells. We have studied the influence of v-erbA on proliferation and differentiation of avian myoblasts. Secondary quail myoblast cultures were infected either with an avian retrovirus carrying the v-erbA oncogene in association with the neomycin resistance gene, or with a control deleted v-erbA/neoR alpha retrovirus. We report here that v-erbA expression led to an increase in myoblast proliferation and to a surprising stimulation of quail myoblast terminal differentiation. In addition, these effects occurred in the presence or absence of T3, and v-erbA did not suppress T3 influence on myoblasts. Transient transfection assays demonstrated that, in contrast to its action in HeLa cells, v-erbA was unable to repress the transcriptional activation of a TRE-CAT reporter gene by liganded c-erbA alpha receptors in quail myoblasts. We also observed that the AP-1/c-erbA/v-erbA interactions are not functional in quail myoblasts. These data suggest that, in these cells, v-erbA action does not interfere with T3 induced mechanisms. They also demonstrate a cell specificity for the v-erbA pathway. Lastly, expression of c-erbA/v-erbA chimeric proteins and of the S61G v-erbA mutant indicates that the DNA binding domain of v-erbA, and more specifically serine 61, is directly involved in the enhancement of myoblast differentiation by the oncoprotein.

Animals↗

PubMed1993

Triiodothyronine influences quail myoblast proliferation and differentiation.

The influence of triiodothyronine (T3) on avian myoblast proliferation and differentiation was studied in secondary cultures using plating densities of 2,500 and 7,000 cells/cm2. Culture media were depleted of T3 (control myoblasts) and increasing amounts were then added to concentrations of 0.6, 3 and 15 nM T3 (treated myoblasts). Independent of the cell density, T3 induced a dose-related decrease in myoblast proliferation measured by cell number, doubling time and 3H-thymidine incorporation. However, with the lower plating density, this influence was delayed, occurring only after the third day of culture for 0.6 nM T3-treated myoblasts and simultaneous with the onset of myosin heavy chain accumulation. Moreover, when myoblasts were exposed to BrdU for 48 h, the T3 growth inhibitory effect disappeared, thus showing that this effect was clearly linked to differentiation. In addition, we have shown that T3 induced an early fusion of myoblasts: 65% of the maximal value of the fusion index was reached on day 3 in the T3-treated cells in comparison to 25% in the control myoblasts. This hormone also enhanced accumulation of muscle-specific proteins (connectin, acetylcholine receptors, myosin heavy chain), tested by cytoimmunofluorescence, ELISA, binding experiments and Western blot. All these results show that T3 increased myoblast differentiation through a pathway including myoblast withdrawal from the cell cycle. The influence of T3 could partly explain its previously reported positive effect on the number of muscle fibers.

Animals↗

PubMed1990

Thyroid function in the newborn lamb. Physiological approach of the mechanisms inducing the changes in plasma thyroxine, free thyroxine and triiodothyronine concentrations.

Several experiments were performed to study the mechanisms inducing the neonatal rises in plasma iodothyronine concentrations in lambs. TSH levels rose during the first 4 to 8h of life, whereas plasma T4 an T3 concentrations increased only from birth to respectively 2 and 1h; the rise in free T4 levels was longer and more important than the rise in total T4. Only T4 changes were strongly related to the extent of TSH increase. The neonatal TSH surge was inhibited by delaying the first milk intake, indicating a great importance of the early nutritional status; in these conditions, the neonatal T4 rise did not occur, whereas the T3 increase was not affected; therefore, in contrast to T4, the T3 increase occurring at birth is not TSH-dependent. As in thyroidectomized lambs continuously infused with T4, plasma T3 concentrations did not increase at birth, it appears that the neonatal T3 surge probably has a thyroidal origin. These results raise the possibility of the existence of a specific stimulator of thyroidal T3 secretion, at least in the newborn lamb. In addition, comparison of the respective T4 increases, at birth or after TSH stimulation in 24 h-old animals, suggests that the ability of the thyroid to respond to a sustained stimulation is strongly reduced at birth. Lastly, neonatal changes in the affinity and/or capacity of carrier proteins for T4, perhaps partly induced by the observed simultaneous rise in free fatty acid levels, could explain that plasma T3 concentrations remained elevated despite a decrease in total T4 levels from 2 h after birth.

Animals↗

PubMed1990

Unusual features of neonatal thyroid function in small-for-gestational-age lambs. Origin of plasma T4 and T3 deficiencies.

Thyroid function was studied in small for gestational age (SGA) or control newborn lambs. Neonatal changes in plasma concentrations of TSH, T3, rT3, total and free T4 were monitored, and thyroid scintigraphs were performed. Responsiveness of the hypothalamic-pituitary-thyroid axis to cold exposure and TRH or TSH administration was assessed. In addition, T4 and T3 kinetic studies were performed. In agreement with results obtained in babies, plasma T3, total T4 and free T4 concentrations were depressed in low birth weight animals, whereas TSH and rT3 levels were not affected. Thyroid size expressed relatively to the body weight was higher in SGA animals, thus suggesting that a partial compensation for low thyroid hormone levels had occurred during the fetal life. Plasma TSH and T4 concentrations increased by a same extent after exposure to cold and TRH or TSH administration in SGA and control lambs; however, the rise in T3 levels was depressed in the former in all stimulation tests. T3 and T4 production rates were similar in the two experimental groups. In SGA lambs, the metabolic clearance rate and the total distribution space of these two hormones were significantly increased; the fast T3 pool was higher, and the slow T3 pool lower than in control animals. All these results demonstrate that, despite low circulating thyroid hormone concentrations, SGA lambs are not hypothyroid. An increased T4 and T3 storage in the extravascular compartment is probably the major factor involved in the occurrence of this plasma deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Cardiorespiratory functions in the fetal llama.

Factors which allow the adaptation of adult llamas to oxygen limitation include principally: low P50, small elliptical red cells with high hemoglobin concentration, high muscle myoglobin concentration, high capillary density and a more efficient O2 extraction at tissue levels. The fetal llama is known to have blood with a low P50 but it is not known whether it has further cardiorespiratory adaptations which could allow it to cope with a low oxygen milieu. To investigate this, we have measured fetal blood flow and blood oxygen content in 8 fetal llamas and compared the findings to similar measurements in 10 low altitude bred fetal sheep, during the last third of gestation. The llamas were born and raised at 4500 m. They were brought to Santiago (586 m) and were studied one week later. The results show that there was higher hemoglobin concentration and higher oxygen capacity in blood from the fetal llama compared to the fetal sheep. Fetal llama combined ventricular output and umbilical blood flow were less than one fourth of those found in fetal sheep. Regional blood flows and oxygen delivery to fetal tissues were in most cases less than half those found in the fetal sheep. Calculated vascular resistances in the fetal llama in almost all vascular beds are higher than those in fetal sheep. These studies suggest that basal fetal llama oxygen uptake is maintained due to an increased oxygen extraction by fetal llama tissues. This increased oxygen extraction may be the result of a high capillary density.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Thyroid hormone and growth: relationships with growth hormone effects and regulation.

For some years, research in the field of growth endocrinology has been mainly focused on growth hormone (GH). However, it appears that GH does not always control growth rate. For instance, it does not clearly influence intra-uterine growth: moreover, although the results of GRF or GH administration appear convincing in rats, pigs or heifers, this is not the case in chickens and lambs. In addition, GH does not always clearly stimulate somatomedin production, particularly diring food restriction and fetal life, and in hypothyroid animals or sex-linked dwarf chickens. In such situations, this phenomenon is associated with a reduced T3 production, suggesting a significant influence of thyroid function on GH action, and more generally, on body growth. In fact, numerous data demonstrate that thyroid hormone is strongly involved in the regulation of body growth. In species with low maturity at birth, such as the rat. T4 and T3 affect postnatal growth eleven days earlier than the appearance of GH influence. In contrast to GH, thyroid hormone significantly influences fetal growth in sheep. Moreover, the body growth rate is clearly stimulated by T3 in dwarf animals. In addition to its complex metabolic effects involved in the general mechanisms of body growth, thyroid hormone stimulates the production of growth factors, particularly EGF and NGF. Moreover, it affects GH and somatomedin production and also their tissue activity. All these results strongly suggest that it would be difficult to study GH regulation and physiological effects without taking thyroid function into account.

Animals↗

PubMed1989

Influence of experimental acidosis on the concentrations of thyreostimulin (TSH) and iodothyronines (total T4, free T4, T3) in the plasma of the newborn lamb.

The effects of acute acidosis on neonatal thyroid function were studied by infusing HCl for 4 h in 42 to 54-h-old lambs. Animals of the same age, used as controls, were simultaneously infused with physiological saline. HCl infusion induced a sharp decrease in blood pH and total restoration did not occur before 48 h. When compared to control lambs, this experimental acidosis was associated with slight, but significant, decreases in plasma TSH, total T4, free T4 and total T3 levels, and in values of the free T4/total T4 ratio; the T3/FT4 ratio was not affected. The values of RT3/FT4 ratio were significantly increased in acidotic lambs. It is concluded that acidosis induced only modest secretory changes in neonatal thyroid function and slightly reduced the proportion and the amount of free T4.

Acidosis↗

PubMed1989

Influence of tri-iodothyronine or lipid administration on the response of the pituitary-thyroid axis to exposure to cold in the newborn lamb.

The influence of the administration of tri-iodothyronine (T3) or a solution of soya oil and egg lecithin on the response of the pituitary-thyroid axis to moderate exposure to cold (4 degrees C for 4 h) was studied in 24-h old lambs. In control lambs, plasma concentrations of TSH. T3 and total and free thyroxine (T4) rose significantly whereas plasma concentrations of reverse T3 remained unchanged during the test. In lambs injected i.v. with a small amount of T3 (1.23 nmol/kg) 30 min before the onset of exposure to cold, plasma concentrations of TSH, reverse T3 and total and free T4 did not change during the test. Administration of lipid 30 min before exposure to cold induced, as expected, a sharp rise in plasma free fatty acid (FFA) concentrations and a transient increase in free T4 concentrations. In these animals, plasma concentrations of TSH increased during the test as observed in control lambs, but plasma concentrations of T3, reverse T3 and total T4 did not show any significant change, whereas free T4 levels decreased during the first 2 h. These results strongly suggest, in contrast to previous results, that T3 exerts a negative feedback upon the hypothalamic-pituitary-thyroid axis in the newborn lamb. Moreover, it appears that a rise in plasma concentrations of FFA could affect neonatal thyroid function.

Animals↗

PubMed1989

Pituitary-thyroid axis sensitivity and neonatal changes in plasma iodothyronine, thyreostimulin and cortisol levels in the preterm lamb: comparison of two experimental models.

The influence of a 7 days prematurity, induced by oestrogen or dexamethasone injection to the mothers, on neonatal changes in plasma T4, T3, reverse T3 (rT3), TSH and cortisol levels was studied in 6 full term, 6 oestrogen preterm and 6 dexamethasone preterm lambs. In addition, the pituitary-thyroid axis sensitivity was assessed by the magnitude of the response to TRH administration. At birth, plasma cortisol and T3 levels, as the value of the T3/T4 ratio, were significantly lower in the two groups of preterm lambs than in full term animals; however, whereas plasma T3 concentrations and values of the T3/T4 ratio remained low in oestrogen lambs, they were quickly restored and elevated T3 levels associated to high T4 levels could be even observed in dexamethasone lambs; in this last group, these abrupt changes could be a consequence of raised TSH plasma concentrations recorded at birth. Moreover, if plasma rT3 levels and values of the rT3/T4 ratio were similar during the first hours of life in dexamethasone and full-term lambs, they were significantly higher in oestrogen animals. The responsiveness of the pituitary-thyroid axis to TRH was normal in dexamethasone animals, but was significantly enhanced in oestrogen ones, probably as a consequence of low T3 levels.

Animals↗

PubMed1989

Effects of transient, corrected ovine maternal hypocalcaemia on neonatal endocrine and metabolic function.

The neonatal changes in plasma levels of thyroid stimulating hormone, iodothyronines, cortisol, insulin, glucose, urea and representative parameters of lipid metabolism, were monitored in eight control lambs and 10 lambs born from hypocalcaemic mothers. Eight hours post partum, plasma total lipid, free fatty acids, cholesterol and phospholipid levels were higher in animals from hypocalcaemic mothers than in control lambs. Moreover, these lambs were clearly hyperthyroid during, at least, the first 48 hours of life. In lambs born from hypocalcaemic mothers, plasma insulin levels were depressed, despite normal glucose concentrations. Plasma cortisol levels were higher than in control lambs, suggesting an endocrine response to a prolonged stress. All these results showed that hypocalcaemia and related metabolic events occurring near the term of pregnancy in ewes could induce neonatal hyperthyroidism, hypoinsulinaemia and metabolic alterations in their offspring.

Animals↗

PubMed1987

Effects of TRH and GRF administration on GH, TSH, T4 and T3 secretion in the lamb.

The effects of various amounts of thyrotropin-releasing hormone (TRH) injected subcutaneously or intravenously (alone or in combination with growth hormone-releasing factor: GRF 1-44) on growth hormone (GH), thyroid-stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3) were studied in the plasma of 2-week, 2-month and 3-month old lambs. After subcutaneous TRH administration, increases in plasma TSH, T4 and T3 levels were equivalent, whatever the amount of TRH used (1,2,5 or 10 micrograms/kg). These responses lasted longer after 5 and 10 micrograms/kg. After intravenous TRH administration in 2-week old lambs, the maximal increase in plasma TSH levels occurred after the injection of 0.25 microgram/kg. However, plasma T4 and T3 responses were not different, whatever the amount used. As previously, the amount of TRH affected the duration of these responses more than the magnitude of the pituitary-thyroid axis response. Whatever the injection route, amount used or animal age, TRH alone did not increase GH secretion in lambs. However, it slightly delayed the GH response to GRF. GRF did not affect the response of TSH and T4 to TRH; however it could inhibit T3 increase. In conclusion, in contrast to results obtained in calves by Hodate et al. (1985), TRH did not enhance GH secretion in lambs but, as expected, induced sharp increases in plasma thyroid hormone levels. Its classification as a "growth factor" is therefore questionable, at least in lambs.

Animals↗

PubMed1987

Effects of food restriction on cortisol, TSH and iodothyronine concentrations in the plasma of the newborn lamb.

The influence of food restriction, applied from birth to 36 h post partum, on neonatal thyroid function was studied in newborn Limousin x Romanov lambs. The control animals (n = 18) had free access to the mother and suckled ad libitum. Restricted lambs (n = 16) were removed from the mother and received limited amounts of colostrum in proportion to birth weight; 8 lambs were supplemented with lactose (30 g/l of colostrum). Plasma glucose and free fatty acid levels were significantly lower in restricted lambs, whereas urea levels were elevated. Plasma cortisol concentrations in control animals decreased during the period studied, but rose during the first 8 h of life in restricted lambs. Lactose supplementation only partially restored glucose and urea levels. Food restriction induced considerable modifications in neonatal thyroid function. The postpartum rise in plasma thyroid-stimulating hormone (TSH), thyroxine (T4) and free T4 levels occurring in control lambs was inhibited in restricted animals. However, the surge in plasma triiodothyronine (T3) levels was not affected, suggesting that this change was not related to physiological neonatal TSH hypersecretion. Thereafter, thyroid hormone concentrations decreased sharply during food restriction, whereas reverse T3 levels remained higher than in the controls. In response to these T4 and T3 deficiencies, plasma TSH levels rose only in lactose-supplemented animals. In agreement with the significant modifications in the values of the T3/free T4 and reverse T3/free T4 ratios, the abrupt changes in T3 and reverse T3 levels suggest that food restriction affected the peripheral conversion of T4 into T3 and reverse T3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Neonatal changes in plasma cortisol, free and total iodothyronine levels in control and hypotrophic lambs.

Neonatal changes in plasma free and total iodothyronines, cortisol, glucose and urea levels have been studied in 8 control (birthweight greater than or equal to 2.5 kg) and 16 hypotrophic lambs (birthweight less than 2.5 kg) receiving limited amounts of colostrum during the first 36 h of life and then fed ad libitum. During the period of colostrum feeding, plasma glucose levels were low in both groups and increased after the onset of ad libitum feeding; they were significantly lower in hypotrophic animals from birth to 36 h. Plasma urea levels increased during the period of colostrum feeding and decreased thereafter in all animals. At birth, they were significantly higher in hypotrophic lambs. Over the entire period studied (20 d), plasma levels of total T4, free T4, total T3 and free T3 were markedly lowered in hypotrophic lambs without alterations in the values of the T3/free T4 ratio. No differences could be observed in plasma reverse T3 and cortisol levels. For all blood parameters recorded, the neonatal changes were parallel in the two groups of lambs. In agreement with hypoglycemia and hyperuremia observed at birth in hypotrophic lambs, with the litter size recorded for each experimental group and with previous results, placental insufficiency linked to a large litter size gestation could be at the origin of low thyroid hormone levels.

Animals↗

PubMed1986

Plasma free and total iodothyronine levels in the newborn lamb. Physiological considerations.

Neonatal changes in plasma total and free iodothyronine levels were monitored in 18 Limousin X Romanov suckling lambs (experiment 1) and 24 Limousin X Romanov animals bottle-fed in standardized conditions (experiment 2). In the two experiments, plasma free T3 levels were closely related to total T3 levels, whereas some differences could be observed between total and free plasma T4 levels. The neonatal rise in free T4 in particular was higher than that observed for total T4 levels. Consequently, the enhancement of T4 availability for T3-generating cells could partly explain the neonatal T3 surge. In addition, plasma reverse T3 levels decreased progressively during the first 48 h of life in suckling lambs. These results suggest also that hypotrophy and/or nutritional status could affect neonatal thyroid function: plasma active iodothyronine levels decreased sharply in bottle-fed lambs (birthweight : 2.29 Kg) compared to suckling ones (birthweight : 3.57 Kg), whereas reverse T3 levels increased.

Animals↗

PubMed1986

Influence of hypothyroidism on the lipolytic activity of norepinephrine in the newborn lamb.

The effects of hypothyroidism on the lipolytic activity of norepinephrine were assessed in the newborn lamb. Lambs were separated into three groups: group A were controls; groups B and C were made hypothyroid by administration of benzylthiouracil from birth until 11 days of age. In control lambs, plasma free fatty acid concentrations, used as an index of lipolytic activity, increased significantly (plus 0.45 mmol/l) during the infusion of norepinephrine, whereas they did not change in hypothyroid lambs (group B). Adding thyroxine and tri-iodothyronine to the infusion medium (group C) immediately restored the free fatty acid response to norepinephrine in hypothyroid lambs (plus 0.41 mmol/l). These results suggest that thyroid hormones could modulate the lipolytic activity of catecholamines in the newborn lamb without a latent period.

Animals↗

PubMed1985

Endocrine activity in preterm and full-term lambs. 1. Adrenal response to synacthen. 2. Thyroid response to ovine thyroid-stimulating hormone or thyrotropin-releasing hormone.

Neonatal endocrine status was studied in 14 lambs born 7 days before term, after estrogen injection into the ewes, and in 15 full-term animals. Plasma cortisol and triiodothyronine (T3) levels were depressed during the first hours of life in preterm lambs and plasma reverse T3 levels were significantly higher than in controls. The rise in plasma cortisol levels after Synacthen injection was significantly lowered by prematurity, suggesting reduced sensitivity of the adrenal cortex to ACTH. After ovine TSH injection, plasma thyroxine (T4) levels increased during a shorter period of time in preterm lambs, resulting in a lowered T4 rise; the T3 response was not affected by prematurity. After TRH injection, the rises in plasma T3 and T4 levels were significantly higher in preterm than in full-term lambs, suggesting a pituitary hypersensitivity to TRH linked to prematurity. Moreover it appeared that the response of reverse T3 to TSH or TRH was very weak.

Adrenal Cortex↗