Biomedical subjects

C Aceves

Publications and source records attributed to C Aceves.

16 recordsLinked to original sources

PubMed2006

Uptake and antiproliferative effect of molecular iodine in the MCF-7 breast cancer cell line.

This study analyzes the uptake and antiproliferative effect of two different chemical forms of iodine, iodide (I-) and molecular iodine (I2), in MCF-7 cells, which are inducible for the Na+/I- symporter (NIS) and positive for pendrin (PDS). The mouse fibroblast cell line NIH3T3 was used as control. Our results show that in MCF-7 cells, I- uptake is sustained and dependent on NIS, whereas I2 uptake is transient with a maximal peak at 10 min and a final retention of 10% of total uptake. In contrast, no I- was taken up by NIH3T3 cells, and although I2 was captured with the same time pattern as in MCF-7 cells, its uptake was significantly lower, and it was not retained within the cell. The uptake of I2 is independent of NIS, PDS, Na+, and energy, but it is saturable and dependent on protein synthesis, suggesting a facilitated diffusion system. Radioiodine was incorporated into protein and lipid fractions only with I2 treatment. The administration of non-radiolabeled I2 and 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid (6-iodolactone, an iodinated arachidonic acid), but not KI, significantly inhibited proliferation of MCF-7 cells. Proliferation of NIH3T3 cells was not inhibited by 20 microM I2. In conclusion, these results demonstrate that I2 uptake does not depend on NIS or PDS; they suggest that in mammary cancer cells, I2 is taken up by a facilitated diffusion system and then covalently bound to lipids or proteins that, in turn, inhibit proliferation.

Animals↗

PubMed2004

Has the mammary gland a protective mechanism against overexposure to triiodothyronine during the peripartum period? The prolactin pulse down-regulates mammary type I deiodinase responsiveness to norepinephrine.

Peripartum is a crucial period for mammary gland final differentiation and the onset of lactation. Although the 'trigger' for lactogenesis depends on several hormones, a key factor is the peripartum prolactin (PRL) pulse whose deletion results in a failure to initiate milk production. Other hormones having a critical role during this period but exerting a contrary effect are the thyronines. A transitory hypothyroidism occurs at peripartum in serum and several other extrathyroidal tissues, whereas the induction of hyperthyroidism during late pregnancy is associated with the absence of lactation after delivery. We analyzed the mammary gland during pregnancy and lactation for: (a) the type and amount of thyroid receptors (TRs), (b) the local triiodothyronine (T3) generation catalyzed by type I deiodinase (Dio1), (c) the Dio1 response to norepinephrine (NE) and (d) the effect on Dio1 and TRs of blocking the PRL pulse at peripartum. Our data showed that during pregnancy the mammary gland contains Dio1 in low amounts associated with the highest expression of TRalpha1; whereas during lactation the gland shows high levels of both Dio1 and TRalpha1. However, at peripartum, both TRs and Dio1 decrease, and Dio1 becomes refractory to NE. This refractoriness disappears when the PRL pulse is blocked by the dopamine agonist bromocriptine. This blockade is also accompanied by a significant decrease in cyclin D1 expression. Our data suggested that the peripartum PRL pulse is part of a protective mechanism against precocious differentiation and/or premature involution of the alveolar epithelium due to T3 overexposure.

Animals↗

PubMed2003

Liver 5'-deiodinase activity is modified in rats under restricted feeding schedules: evidence for post-translational regulation.

Restricted feeding schedules (RFSs) produce a behavioral activation known as anticipatory activity, which is a manifestation of a food-entrained oscillator (FEO). The liver could be playing a role in the physiology of FEO. Here we demonstrate that the activity of liver selenoenzyme deiodinase type 1 (D1), which transforms thyroxine into triiodothyronine (T3), decreases before food access and increases after food presentation in RFSs. These changes in D1 activity were not due to variations in D1 mRNA. In contrast, a 24 h fast promoted a decrease in both D1 activity and mRNA content. The adjustment in hepatic D1 activity was accompanied by a similar modification in T3-dependent malic enzyme, suggesting that the local generation of T3 has physiological implications in the liver. These results support the notion that the physiological state of rats under RFSs is unique and distinct from rats fed freely or fasted for 24 h. Data also suggest a possible role of hepatic D1 enzyme in coordinating the homeorhetic state of the liver when this organ participates in FEO expression.

Animals↗

PubMed2001

Effect of suckling and adrenergic stimulation on peripheral deiodination in lactating rats: differential expression of type 1 deiodinase mRNA forms.

Previous works led us to propose that peripheral iodothyronine deiodination is mainly regulated by the reciprocal interaction between the thyroid and the sympathetic nervous system (SNS). In this study, we analyzed the role suckling exerts, through SNS activation, upon deiodination of thyronines in liver, heart, brown adipose tissue and mammary gland during lactation. Our results showed that resuckling causes a concurrent stimulatory response on deiodinase type 1 (D1) in heart and mammary gland, but not in liver and brown adipose tissue. The stimulatory response was mimicked by norepinephrine and by the beta-adrenergic agonist isoproterenol, through the overexpression of the large form of D1 mRNA. These results suggested that, during lactation, peripheral thyronine deiodination is co-ordinated by the SNS, and suckling is a major modulatory influence.

Adipose Tissue, Brown↗

PubMed1999

Mammary type I deiodinase is dependent on the suckling stimulus: differential role of norepinephrine and prolactin.

Mammary deiodinase type I (M-D1) is present only during lactation and exhibits a clear direct correlation with lactation intensity (size of litters). The present work shows that M-D1 is suckling dependent and that intervals between suckling periods no longer than 12 h are essential to maintain this activity. Moreover, we find that with only 15 min of resuckling in 12-h nonsuckled mothers, the 50% decrease in both M-D1 messenger RNA and enzymatic activity could be restored to control values. This restorative effect by suckling may involve pre- and posttranscriptional mechanisms in which norepinephrine and PRL play important roles. Norepinephrine elicits a potent stimulatory effect on M-D1 messenger RNA and enzyme activities, whereas PRL only increases M-D 1 activity and may modulate the enzyme response to norepinephrine. Oxytocin and GH had no effect. These data suggest that the adrenergic nervous system and PRL could directly participate in mammary energetic expenditure, regulating the local T3 supply.

Animals↗

PubMed1999

Mammary gland sympathetic innervation is a major component in type 1 deiodinase regulation.

Recent observations have shown that in lactating rats previously deprived of suckling, either suckling stimulus or ip injection of norepinephrine was capable of increasing mammary deiodinase type 1 (M-D1) mRNA content and enzyme activity. In the present work, we show that intact efferent sympathetic mammary innervation is required to restore both mammary D1 mRNA content and enzyme activity, whereas suckling-induced secretion of catecholamines from the adrenal glands does not seem to participate in M-D1 enzyme regulation. The data also indicate that the sympathetic reflex activation in response to suckling involves two complementary autonomic components: (1) activation, presumably through mammary segmental arrangement affecting neighboring mammary glands; and (2) an individual reflex regulatory mechanism capable of maintaining M-D1 activity within each mammary gland. In addition to these findings, we show that the suckling-induced sympathetic activation of M-D1 activity could be blocked by prior activation of ductal mechanoreceptors. This set of regulatory and counterregulatory mechanisms seems to ensure the optimal control of mammary energetic expenditure according to litter size.

Adrenal Glands↗

PubMed1997

Mammary gland type I iodothyronine deiodinase is encoded by a short messenger ribonucleic acid.

Lactating rat mammary gland expresses a deiodinating activity that, on the basis of kinetic characteristics, corresponds to the so-called 5'-deiodinase type I (D1). In the present study we amplified and sequenced several D1 complementary DNA (cDNA) fragments from rat lactating mammary gland. The mammary cDNA was found to be identical to the previously reported rat liver cDNA in the coding region, but 465 nucleotides shorter on its 3'-untranslated region, suggesting that the D1 is the same in both tissues. D1 messenger RNA (mRNA) was also detected by reverse transcriptase-PCR in mammary glands from puberal and late pregnant rats, but not in virgin animals. Densitometric analysis showed a close and direct correlation between mRNA content and enzyme specific activity in mammary gland. Our results also show that rat liver contains both D1 mRNA forms and that the large form may respond to the thyroid status. These data suggest a differential and organ-specific expression of these mRNA forms, which could play a role in the functional regulation of D1 activity.

Animals↗

PubMed1994

Influence of thyroid status on TRH metabolism in rat olfactory bulb.

The effect of thyroid hormones (TH) on the metabolism of thyrotropin-releasing hormone (TRH) in the olfactory bulb (OB) was compared with the hypothalamic response to TRH. Two methods were used to induce hypothyroidism: propylthiouracyl-methimazole (PTU-M) or 131I treatment. Hyperthyroidism was produced by 3,3',5-triiodo-L-thyronine (T3) injections to the hypothyroid animals. With PTU-M treatment, paraventricular TRH mRNA levels increased 57% and returned to the euthyroid level with T3 treatment. In OB, TRH mRNA was not altered. The TRH content was unaffected in the mediobasal hypothalamus of PTU-M-treated animals whereas it was reduced in OB (31%) with no further response upon T3 treatment. 131I-induced hypothyroidism did not modify the OB TRH content but it was decreased (31%) in hyperthyroids. In the median eminence, TRH increased 26% in hypothyroids, and the response was reversed with T3. Our results demonstrate that treatments that change thyroid status can alter TRH levels in the OB, probably at a translational or postranslational level, though the effects may be pharmacological.

Animals↗

PubMed1993

Ontogenesis of iodothyronine deiodinase activities in brain and liver of the chick embryo.

The ontogeny of 5'-monodeiodinase activity (5'-MA) was analyzed in chick embryo brain and liver tissue. The enzymatic type predominant in this path and the activity of the deactivating pathway (5 MA-III) were determined during certain periods of neural development in both organs. Results show that T3 is predominantly formed in both organs during the first third of embryogenesis (from day 5) until neuroblast proliferation (day 13). Within this lapse, the slow type II enzyme (insensible to propylthiouracil) is present in the brain, whereas in the liver the predominating enzyme is type I (the rapid enzyme). Further along the synaptogenesis period (day 14-17), 5' deiodination virtually disappears in the brain, the hepatic type I enzyme switches to the slow autoconsume enzyme (type II), and 5 MA-III levels increase significantly in both organs. Finally, on days 18-20 (perinatal period) the 5' pathway reaches the highest levels observed throughout the study in both tissues. Associated to this increase, liver enzymatic activity returns to type I. During this period, 5 MA-III is reduced by 40% in the brain and disappears from the liver. Together, these data strengthen the notion of a protective mechanism against brain overexposure to T3 during synaptogenesis and suggest that the protective mechanism also involves the regulation of extraneural deiodinases.

Animals↗

PubMed1991

Neuroendocrine regulation of adrenal 5'-monodeiodination during acute cold exposure in the rat. I. Effects of hypophysectomy.

Circulating levels of T4, T3, corticosterone, noradrenaline, and adrenaline, as well as 5'-monodeiodinase activity (5'-MA) were measured in control and hypophysectomized rats acutely exposed to cold environment (15-120 min, 4 C). In addition to the well known activation of the sympathoadrenomedullary system and the hypothalamic-pituitary-adrenal and-thyroid axes, cold exposure was followed by a rapid and sustained increase of 5'-MA in the hypothalamus, and a byphasic course of activation in the adrenal gland in control rats. The adrenal rapid activation (30 min) corresponded to the medulla and the slower activation (120 min) to the cortex. Both, the basal adrenal 5'-MA and the response to cold in adrenal and hypothalamus were 2-fold higher in hypophysectomized rats compared to control. The time course of enzyme activation in these structures suggests that: 1) organ-specific increases in 5'-MA may be associated to a simultaneous rise in their metabolic and/or functional activity, 2) the triggering mechanisms involves an immediate sympathetic signal activating the hypothalamic-adrenal medulla response and a pituitary signal eliciting a slower adrenocortical response, and 3) the compensatory sympathetic hyperactivity after panhypopituitarism contribute to enhance both the adrenal enzyme basal activity and the hypothalamic and adrenal hyperresponse to cold stress.

Adrenal Cortex↗

PubMed1990

Vestibular site of action of hypothyroidism in the pigmented rat.

The vestibular cell type affected by congenital hypothyroidism (CH) was investigated by measuring the activity of glutamate decarboxylase (GAD) and choline acetyltransferase (ChAT), synthesizing enzymes of putative afferent (GABA) and efferent (acetylcholine, ACh) neurotransmitters and thus, respectively, hair cell I and II (HC-I, HC-II), and efferent terminal (ET) marker enzymes, in vestibular homogenates of control, congenitally hypothyroid rats (CHR) and in thyroxine-replaced CHR (CHR-T4) whose postnatal age ranged from 20 to 60 days old. In the vestibule, CH-II and its efferent cholinergic contacting bouton mature prior to thyroid function whereas HC-I-differentiation and its efferent synapse arrival are the latest events in vestibular maturation. Therefore, a differential effect of CH upon GAD and ChAT in CHR could be anticipated. In control rats as in CHR the magnitude of GAD was the same with time starting on the 20th day. In CHR, ChAT gradually diminished beginning on day 28 to become 45% decreased with respect to control on the 60th postnatal day. Prevention of ChAT decrease in CHR by early administration of thyroxine (T4), a striking diminution of T4 and triiodothyronine (T3) in CHR serum and a normal level of these hormones found in CHR-T4 corroborated thyroid involvement. These results confirm the preference of hypothyroidism to affect cholinergic cell types (or compartments) of late maturation (HC-I-containing ET and hence 45% ChAT decrease) leaving HC-I, HC-II and HC-II-connecting ET untouched, supported by a 55% remanent ChAT and a constant GAD activity regardless of time and treatment.

Animals↗

PubMed1989

Circulating thyronines and peripheral monodeiodination in lactating rats.

The well known metabolic and endocrine adaptive responses accompanying lactation include a change in circulating thyronines that resembles the so-called euthyroid sick syndrome. To analyze the role played by tissue monodeiodination in this state, circulating levels of thyronines as well as hepatic and mammary 5'-monodeiodinative activity (5'MA) were assessed during lactation in rats. Results show that the serum iodothyronine changes that accompany lactation are associated with a significant decrease in hepatic 5'MA and a simultaneous increase in mammary 5'MA. These changes begin within the first postpartum day, are proportional to lactation intensity (litter size), and disappear 48 h after either precocious (1st postpartum day) or natural (21st postpartum day) weaning. These data demonstrate that the compartmentalized change in energy expenditure characteristic of lactation is accompanied by organ-specific and opposite adjustments in hepatic and mammary monodeiodinative pathways.

Animals↗

PubMed1989

Type I, 5'-monodeiodinase activity in the lactating mammary gland.

Mammary homogenates from lactating, weaned, pregnant, and nonpregnant rats were analyzed for 5'-monodeiodinase activity (5'-MA). Only lactating glands exhibited significant enzyme activity. Competitive analysis showed that mammary 5'-MA is not inhibited by high (10 microM) concentrations of T4 or T3, but is highly sensitive to prophythiouracil (5 mM). Kinetic parameters demonstrate an acompetitive bisubstrate enzymatic mechanism known as the ping-pong type. The Km and maximum velocity for rT3 were 0.40 microM and 1.42 nmol/mg.min, respectively. These results provide the first evidence that 5'-MA is present in the lactating mammary gland and suggest that this enzymatic activity corresponds to type I enzyme.

Animals↗

PubMed1988

Tissue-specific regulation of pyroglutamate aminopeptidase II activity by thyroid hormones.

Among the enzymes capable of degrading thyrotropin-releasing hormone (TRH) in vitro, two pyroglutamate aminopeptidases (PGA) are specific for TRH: thyroliberinase, a seric enzyme and PGAII, a membrane-bound peptidase. The effect of thyroid hormone status on the activity of these enzymes was evaluated in serum and various tissues. Only in adenohypophysis, triiodothyronine treatment increased PGAII to 376% of control; hypothyroidism produced the reverse effect (decrease to 23% of control). As previously reported, similar changes were observed for thyroliberinase. TRH degradation at the adenohypophysis level may participate in the negative feedback control of thyroid hormones.

Aminopeptidases↗

PubMed1987

Thyroid hormone profile in dairy cattle acclimated to cold or hot environmental temperatures.

Milk yields and the circulating profile of T4, T3 and rT3 were assessed during three different seasons of the year, in first trimester lactating (L) and in dry (D) multiparous holstein cows acclimated to distinct weather conditions. Within the thermoneutral zone (18-28 degrees C; 40-60% RH) and regardless of their geographical location, the thyroid hormone profile in all L-cows (n = 50) resembled the so-called euthyroid sick syndrome (T4, 43.7 +/- 7.7 nmol/l; T3, 1.31 +/- 0.10 nmol/l and rT3, 0.52 +/- 0.08 nmol/l). In both groups of animals the T3/T4 molar ratio was similar within the entire range of climates encompassed in the study. However, both groups exhibited a significant shift in the T3/rT3 molar ratio during cold (10 degrees C; 50%) or hot-dry (34 degrees C; 40%) weather conditions. This shift reaches maximum values (L, 6.5 +/- 1.2; D, 7.9 +/- 1.0 nmoles/l) under hot-humid conditions (28-42 degrees C; 60-90%). The relative increase of T3 levels from comfortable to cold or hot environmental temperatures, was significantly higher in L and D animals (30 vs 12%, respectively). Furthermore, only L-cows exhibited a significant decrease in the rT3/T4 molar ratio during either type of thermoregulatory demands, as well as a significant increase of T4 values under heat-acclimation. These results suggest that heat-acclimation in dairy cattle does not depress thyroid gland activity, and lend further support to the notion that adaptive thermoregulatory mechanisms in homeothermic vertebrates, involve adjustments in the peripheral monodeiodinative pathways of thyroid hormones.

Acclimatization↗

PubMed1985

Homeorhesis during early lactation. Euthyroid sick-like syndrome in lactating cows.

Serum levels of thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) were studied in dry, early (first trimester) and middle (second trimester) lactating purebred Holstein cows. The study encompassed three different seasons: autumn, winter and spring. Under comfortable weather conditions (temperature 22 degrees C; relative humidity, 40%) or moderately hot (28 degrees C; 60%), January and October, respectively, cows in early lactation exhibited significantly lower levels of T4 and T3, and higher values of rT3 than dry or middle lactating animals. In contrast, during May, when environmental temperature increased (34 degrees C; 40%), a clear-cut shift in T3/rT3 ratio occurred, and animals in early lactation exhibited the highest T3 and the lowest rT3 concentrations. These findings suggest that in dairy cattle, peripheral thyroid hormone metabolism plays a major role in regulating the homeorhetic responses involved in the maintenance of high priority functions.

Adaptation, Physiological↗