Biomedical subjects

E Herrera

Publications and source records attributed to E Herrera.

At least 109 records · Page 6Linked to original sources

PubMed1990

High-density lipoprotein subpopulations as substrates for the transfer of cholesteryl esters to very-low-density lipoproteins.

1. Human total HDL (high-density lipoprotein), HDL2 and HDL3 were labelled in vitro by incubation with lipoprotein-deficient serum (LPDS) which contained either [3H]cholesteryl oleate or [14C]cholesterol under different conditions. The lipoproteins were then subfractionated by heparin-Sepharose column chromatography, and three subfractions (A, B and C) were successively eluted from each preparation of HDL, HDL2 and HDL3. When the labelling was done at 37 degrees C for 17 h, the subfractions were homogeneously labelled with [3H]cholesteryl oleate. However, when it was performed for only 30 min at 4 degrees C, the subfractions showed marked differences in the 3H specific radioactivity, which was much higher in the C fractions than in the others. 2. 3H-labelled HDL2 and HDL3 subfractions behaved differently under the precipitant action of heparin-Mn2+; fraction C (the richest in apolipoprotein E) produced the largest amount of radioactive and chemical precipitate. More 3H radioactivity, but not the cholesterol, was precipitated from HDL2 or HDL3 by the reagent, demonstrating that 3H-labelled HDL2 and HDL3 behave like their fraction C, which becomes labelled to the highest specific radioactivity despite having the smallest mass. 3. The incubation of 3H-labelled HDL subfractions with human LPDS and very-low-density lipoprotein (VLDL) at 37 degrees C increased the quantity of 3H radioactivity that was precipitated, in proportion to the amount of VLDL present in the media. These changes were attributable to the action of cholesterol ester transfer protein, since they did not occur at 4 degrees C or when human LPDS was replaced with rat LPDS. 4. Kinetics of the transfer of HDL [3H]cholesteryl oleate to VLDL showed a greater apparent Vmax for fractions A than for fractions B from either HDL2 or HDL3, whereas the apparent Km values were very similar, which suggest that this transfer process is influenced by the apoprotein composition of the donor lipoprotein.

Animals↗

PubMed1990

Differences in the kinetic properties and sensitivity to inhibitors of human placental, erythrocyte, and major hepatic aldehyde dehydrogenase isoenzymes.

(i) The characteristics of the major human hepatic isoenzymes of aldehyde dehydrogenase (ALDH), ALDH I and ALDH II, were compared with the ALDH activities found in human placenta and erythrocytes, (ii) In human liver biopsies, the Km of ALDH I was approximately 7 mumol/L whereas it was 32 mumol/L for ALDH II. The Vmax for ALDH I was 2-3 times greater than the ALDH II Vmax. Human liver ALDH I and II also differed in their sensitivity in inhibitors. Namely, ALDH I was less sensitive to disulfiram than the ALDH II isoenzyme. (iii) ALDH activity in human placenta and erythrocytes was much lower than in liver tissue. Kinetic data showed that placental ALDH isoenzyme had a high Km (in the millimolar range) and increased its activity raising the pH from 7.4 to 8.8, more than the hepatic ALDH I and ALDH II isoenzymes did. Erythrocyte ALDH activity presented a dual component; the smaller one was characterized by a low Km (micromolar range), whereas most of the ALDH activity showed a high Km (millimolar range). (iv) Placental ALDH was resistant to nitrefazole inhibition and was inhibited by disulfiram in a manner similar to the hepatic ALDH I isoenzyme; erythrocyte ALDH was more sensitive to the inhibitory action of disulfiram and nitrefazole. (v) It is concluded that erythrocyte and placental ALDH isoenzymes are different from the hepatic ALDH I and ALDH II forms. It is also suggested that placental and erythrocyte ALDH isoenzymes are different high-Km isoenzymes.

Acetaldehyde↗

PubMed1990

In vivo ethanol elimination in man, monkey and rat: a lack of relationship between the ethanol metabolism and the hepatic activities of alcohol and aldehyde dehydrogenases.

The in vivo ethanol elimination in human subjects, monkeys and rats was investigated after an oral ethanol dosage. After 0.4 g. ethanol/kg of body weight, ethanol elimination was much slower in human subjects than in monkeys. In order to detect a rise in monkey plasma ethanol concentrations as early as observed in human subjects, ethanol had to be administered at a dose of 3 g/kg body weight. Ethanol metabolism in rats was also much faster than in human subjects. However, human liver showed higher alcohol dehydrogenase activity and higher low Km aldehyde dehydrogenase activity than rat liver. Thus, our data suggest a lack of relationship between hepatic ethanol-metabolizing activities and the in vivo ethanol elimination rate.

Alcohol Dehydrogenase↗

PubMed1990

Differences in kinetic characteristics and in sensitivity to inhibitors between human and rat liver alcohol dehydrogenase and aldehyde dehydrogenase.

1. On the basis of kinetic properties and sensitivity to pyrazole inhibition, it is shown that liver alcohol dehydrogenase present in human mainly corresponded to class I and in rat to class ADH-3 which differed in a number of parameters. 2. Two different aldehyde dehydrogenase (ALDH) isoenzymes were detected in both human and rat liver. The human isoenzymes corresponded to the ALDH-I and ALDH-II type. 3. In the rat, one isoenzyme had low Km and showed similar activity than in human liver but differed in their sensitivity to both disulfiran and nitrofazole inhibition whereas the other presented high Km and showed greater activity than the human one. 4. Caution must be therefore paid when extrapolating to human subjects the data on ethanol metabolism obtained with rats.

Acetaldehyde↗

PubMed1989

Rapid effects of insulin and glucose on the hepatic incorporation of gluconeogenic substrates into glyceride glycerol and glycogen.

1. The hepatic utilization of gluconeogenic substrates was investigated shortly after portal infusion of either insulin or glucose in fasted rats. 2. After 20 min of insulin infusion blood glucose concentration decreased. However, neither glucose generation from precursors such as alanine or pyruvate nor their incorporation into fatty acids was modified. Under these conditions, insulin rapidly increased the incorporation of gluconeogenic substrates into the hepatic glyceride glycerol fraction. Insulin treatment led to a decrease in substrate incorporation into liver glycogen. 3. After 20 min of portal glucose infusion both plasma insulin and glucose concentrations increased and the incorporation of pyruvate into hepatic glyceride glycerol and into glycogen was also stimulated. 4. A close relationship was observed between blood glucose concentrations and the level of incorporation of gluconeogenic substrates into liver glycogen. 5. In conclusion, during fasting insulin stimulates the incorporation of gluconeogenic substrates into the glycerol moiety of hepatic glycerides, which may be the preferential mechanism through which fatty acid esterification is accomplished during refeeding. This effect of insulin is rapid and detected even before other classical modifications induced by the hormone such as gluconeogenesis inhibition or lipogenesis activation. Furthermore, the effect is not related to insulin-induced hypoglycemia since glucose infusion mimics insulin action on glyceride glycerol synthesis.

Alanine↗

PubMed1989

Appearance of circulating and tissue 14C-lipids after oral 14C-tripalmitate administration in the late pregnant rat.

Studies were performed to determine whether and/or how dietary lipids participate in maternal hypertriglyceridemia during late gestation in the rat. After oral administration of glycerol-tri(1-14C)-palmitate, total radioactivity in plasma increased more rapidly in 20-day pregnant rats than in either 19-day pregnant rats or virgin controls. At the peak of plasma radioactivity, four hours after the tracer was administered, most of the plasma label corresponded to 14C-lipids in triglyceride-rich lipoproteins (d less than 1.006), and when expressed per micromol of triglyceride, values were higher in pregnant than in virgin rats. The difference was less after 24 hours, although at this time the level of 14C-lipids in d less than 1.006 lipoproteins was still higher in 20-day pregnant rats than in virgins. Tissue 14C-lipids, as expressed per gram of fresh weight, were similar in pregnant and virgin rats, but the values in mammary glands were much higher in the former group. Estimated recovery of administered radioactivity four hours after tracer in total white adipose tissue, mammary glands, and plasma lipids was higher in pregnant than in virgin rats. No difference was found between 20-day pregnant and virgin rats either in the label retained in the gastrointestinal tract or in that exhaled as 14C-CO2 during the first four hours following oral administration of 14C-tripalmitate. These findings plus the known maternal hyperphagia, indicate that in the rat at late pregnancy triglyceride intestinal absorption is unchanged or even enhanced and that dietary lipids actively contribute to both maternal hypertriglyceridemia and lipid uptake by the mammary gland.

Animals↗

PubMed1989

Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes.

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Decreased in vivo rate of ethanol metabolism in the suckLing rat.

Blood concentrations of ethanol and acetaldehyde were determined in suckling rats after a single oral ethanol gavage. These results were compared with the hepatic activities of alcohol and aldehyde dehydrogenase. After intragastric administration of 3 g/kg body weight of ethanol, ethanol concentrations were much higher in suckling rats than in adult animals, especially at 90, 120, and 180 min after its administration. In addition, acetaldehyde concentrations were undetectable in suckling rats as opposed to adult rats, in whom micromolar concentrations were detected. Thus, 5- to 30-day-old rats seem to have a limited capacity for in vivo ethanol metabolism. The analysis of hepatic alcohol dehydrogenase activity revealed that it was very low at birth and it increased progressively with time attaining adult levels after 20 days of life. The alcohol dehydrogenase activity present in the liver of suckling rats presented similar Km values and sensitivity to pyrazole as adult rat liver. Thus, the pattern of in vivo ethanol elimination during the suckling period is not explained by hepatic alcohol dehydrogenase activity. Whether that diminished ethanol metabolism is due to slower intestinal ethanol absorption, different ethanol distribution in the body, or diminished hepatic capacity for NADH reoxidation remains to be studied. At birth, hepatic aldehyde dehydrogenase activity was low and it increased reaching adult levels during the suckling period. Adult levels for the component of low Km were attained earlier than for the component of high Km. The low affinity hepatic aldehyde dehydrogenase component in the newborn was different from that in the adult as assessed by kinetic studies and by its sensitivity to disulfiram.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

PubMed1989

Low intestinal lactase activity in offspring from ethanol-treated mothers.

Some aspects of small intestine maturation have been studied in the newborns from chronic ethanol-treated pregnant rats (25% ethanol in drinking fluid) immediately after birth (before suckling) and after 30 days of life. Litters delivered by mothers fed ad libitum with a standard diet diluted 50% with cellulose were used as a nutritional control. At birth, pups from ethanol-treated mothers showed significant decreases in total intestinal length and thickness, low total lactase activity and low somatostatin intestinal content. The intestinal alterations of these neonatal parameters are not present in newborns from mothers on fiber-diluted diet. From delivery, pups from different experimental groups were nursed by normal lactating dams. At 30 days of age neither of those parameters differed among the groups. We propose that the low levels of total lactase activity in newborns from alcoholic mothers, that are a consequence of a lower intestinal mucosa content, are a direct effect of ethanol in utero on the fetal gastrointestinal system.

Aging↗

PubMed1989

Disposition of ethanol and acetaldehyde in late pregnant rats and their fetuses.

The pattern of ethanol and acetaldehyde appearance in blood after an oral ethanol gavage (4 g/kg body wt) was not different at 12 or 21 days' gestation compared to virgin rats. Five min after maternal ethanol administration, concentrations of ethanol in fetal blood were lower than in maternal blood; however, at 15 min after ethanol administration, fetal and maternal blood levels were similar. Ethanol concentrations in fetal blood and amniotic fluid were already at equilibrium 5 min after ethanol administration. Acetaldehyde concentrations in fetal blood and in amniotic fluid were undetectable at all the times investigated, with the exception of fetuses from two pregnant rats studied 3 h after ethanol administration. Alcohol dehydrogenase activity in fetal liver and in placenta at late pregnancy was very low or undetectable, suggesting a very low rate of ethanol oxidation in vivo. After intravenous administration of acetaldehyde (10 mg/kg body wt), blood acetaldehyde concentrations were higher in pregnant than in virgin rats. Acetaldehyde concentrations in fetal blood and in amniotic fluid were similar to maternal blood at 2, 5, and 30 min after injection. When circulating concentrations of maternal and fetal acetaldehyde, obtained after either ethanol or acetaldehyde administration, were plotted, it was found that fetal blood concentrations of acetaldehyde were only detectable when maternal blood concentrations were greater than 80 microM. Concerning the acetaldehyde oxidation capacity, both the high and low affinity components of aldehyde dehydrogenase activity in fetal liver and placenta were very low as compared with maternal liver. However, aldehyde dehydrogenase activity in fetal liver was much higher than in placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

PubMed1988

Pregnancy and pentobarbital anaesthesia modify hepatic synthesis of acylglycerol glycerol and glycogen from gluconeogenic precursors during fasting in rats.

1. Incorporation of gluconeogenic precursors into blood glucose and hepatic glycogen and acylglycerol glycerol was examined in 24 h-fasted virgin rats by using a flooding procedure for substrate administration. At 10 min after their intravenous injection, the conversion of alanine or glycerol into liver glycogen or acylglycerol glycerol was proportional to glucose synthesis. 2. In 24 h-fasted 21-day-pregnant rats, the incorporation of alanine and glycerol into hepatic acylglycerol glycerol was markedly enhanced compared with the control group. In addition, during fasting at late pregnancy, the proportion of substrates directed to acylglycerol glycerol as compared with the fraction incorporated into glucose was augmented. 3. In pentobarbital-treated fasted rats, the incorporation of both alanine and pyruvate into circulating glucose and into hepatic glycogen and acylglycerol glycerol was increased. Pentobarbital treatment increased the proportion of substrates incorporated into liver glycogen, compared with the fraction appearing in circulating glucose. These changes were concomitant with a marked accumulation of glycogen. 4. The data indicate that, during fasting, gluconeogenesis provides glucose as well as hepatic glycogen and acylglycerol glycerol, independently of whether the substrates enter gluconeogenesis at the level of pyruvate or dihydroxyacetone phosphate.

Anesthesia, Intravenous↗

PubMed1988

Studies with etofibrate in the rat. Part I: Effects on glycerol, free fatty acid and triacylglycerol metabolism.

Etofibrate is the 1,2-ethandiol diester of clofibric acid and nicotinic acid that decreases circulating levels of triacylglycerols and cholesterol. To understand the mechanism by which the drug affects plasma triacylglycerols, normolipemic rats were treated daily with 300 mg of etofibrate/kg body weight or with the medium by a stomach tube. They were decapitated on the 10th day, and showed lower levels of plasma beta-hydroxybutyrate, glycerol, free fatty acids (FFA), total triacylglycerols and cholesterol and VLDL triacylglycerols and cholesterol, whereas glucose and RIA-determined insulin levels were unmodified. Epididymal fat pad pieces from etofibrate-treated rats incubated in vitro released more glycerol but the same amount of FFA to the medium, and had greater uptake of [U-14C]glycerol for [14C]acylglycerol formation. In the presence of heparin, they also showed an enhanced release of lipoprotein lipase activity to the medium. The disappearance from plasma of intravenously administered [1-14C]palmitate was faster in the etofibrate-treated rats, and although they showed a decrease in 14C-esterified fatty acids of neutral lipids in both liver and plasma VLDL, there was an increase in liver 14C-labelled water-soluble components. After intravenous [U-14C]glycerol administration, there was a decrease in plasma VLDL [14C]acylglycerol and [14C]glucose and in liver [14C]acylglycerol, but an increase in plasma [14C]lactate. In the liver, etofibrate treatment heightened the cytosolic glycerol-3-phosphate dehydrogenase activity and the total carnitine concentration, whereas it reduced triacylglycerol and cholesterol concentrations. It is proposed that etofibrate enhances the reesterification of fatty acids and glycerol in adipose tissue, which, together with its augmented lipoprotein lipase activity, may facilitate the clearance of circulating triacylglycerols. These effects may act concomitantly with the decreased synthesis of triacylglycerols, secondary to the increased utilization of their precursors, acyl-CoA and glycerol-3-phosphate, in other pathways, causing the reduction of plasma VLDL triacylglycerols produced by etofibrate treatment.

Adipose Tissue↗

PubMed1988

High liver lipoprotein lipase activity in hyperlipemic developing rats from undernourished pregnant mothers.

To study the potential relationship between circulating triacylglycerol (TAG) levels and lipoprotein lipase (LPL) activity in the newborn rat liver, pups from undernourished or normal control mothers were nursed by normal dams, and studied at 0, 1, 15 or 30 days of age. Plasma TAG levels and liver TAG concentration increased more in pups from undernourished mothers than they did in controls. At birth, liver LPL activity was similarly high in both groups but, whereas in controls it decreased progressively after birth, in pups from undernourished mothers it remained stable until 15 days of age. Results suggest that the hypertriglyceridemia present in pups from undernourished mothers may be responsible for the sustained high LPL activity in their liver which may enhance the hepatic uptake of circulating TAG.

Animal Nutritional Physiological Phenomena↗

PubMed1988

Role of lipoprotein lipase activity on lipoprotein metabolism and the fate of circulating triglycerides in pregnancy.

The mechanism that induces maternal hypertriglyceridemia in late normal pregnancy, and its physiologic significance are reviewed as a model of the effects of sex steroids on lipoprotein metabolism. In the pregnant rat, maternal carcass fat content progressively increases up to day 19 of gestation, then declines at day 21. The decline may be explained by the augmented lipolytic activity in adipose tissue that is seen in late pregnancy in the rat. This change causes maternal circulating free fatty acids and glycerol levels to rise. Although the liver is the main receptor organ for these metabolites, liver triglyceride content is reduced. Circulating triglycerides and very-low-density lipoprotein (VLDL)-triglyceride levels are highly augmented in the pregnant rat, indicating that liver-synthesized triglycerides are rapidly released into the circulation. Similar increments in circulating VLDL-triglycerides are seen in pregnant women during the third trimester of gestation. This increase is coincident with a decrease in plasma postheparin lipoprotein lipase activity, indicating a reduced removal of circulating triglycerides by maternal tissues or a redistribution in their use among the different tissues. During late gestation in the rat, tissue lipoprotein lipase activity varies in different directions; it decreases in adipose tissue, the liver, and to a smaller extent the heart, but increases in placental and mammary gland tissue. These changes play an important role in the fate of circulating triglycerides, which are diverted from uptake by adipose tissue to uptake by the mammary gland for milk synthesis, and probably by the placenta for hydrolysis and transfer of released nonesterified fatty acids to the fetus. After 24 hours of starvation, lipoprotein lipase activity in the liver greatly increases in the rat in late pregnancy; this change is not seen in virgin animals. This alteration is similar to that seen in liver triglyceride content and plasma ketone body concentration in the fasted pregnant rat. In the fasting condition during late gestation, heightened lipoprotein lipase activity is the proposed mechanism through which the liver becomes an acceptor of circulating triglycerides, allowing their use as ketogenic substrates, so that both maternal and fetal tissues may indirectly benefit from maternal hypertriglyceridemia. Changes in the magnitude and direction of lipoprotein lipase activity in different tissues during gestation actively contribute both to the development of hypertriglyceridemia and to the metabolic fate of circulating triglycerides.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗

PubMed1988

Metabolic response to starvation at late gestation in chronically ethanol-treated and pair-fed undernourished rats.

To study the role of undernourishment in the negative effects of ethanol during pregnancy and to determine whether maternal ethanol intake modifies metabolic response to starvation at late gestation, female rats receiving ethanol in their drinking water before and during pregnancy (ethanol group) were compared with animals that received the same amount of solid diet as the ethanol group rats (pair-fed group) and with normal rats fed ad libitum (control group). All animals were killed on the 21st day of gestation, either in the fed state or after 24-hours fasting. The body weight of ethanol rats was lower than that of controls but higher than that of pair-fed rats. When compared with controls, ethanol and pair-fed rats had reduced fetal body weights, whereas fetal body length was reduced only in the former. In the fed state, blood glucose concentration was lower in the ethanol and pair-fed rats and fetuses than in controls. Twenty-four-hour starvation caused a reduction in this parameter only in control and ethanol mothers. In the fed state, maternal liver glycogen concentration was lower in ethanol and higher in pair-fed mothers than in controls. Blood beta-hydroxybutyrate levels were higher in ethanol-treated mothers than in the others, and 24-hour starvation increased this parameter in ethanol and control rats to a greater extent than in the pair-fed ones. Liver triacylglyceride concentration was higher in ethanol-treated mothers than in the other two groups, and starvation caused this concentration to increase in ethanol and control groups but not in the pair-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

PubMed1988

Comparative metabolic effects of chronic ethanol intake and undernutrition in pregnant rats and their fetuses.

Female rats receiving ethanol in the drinking water before and during gestation (ET) were compared to pair-fed animals (PF) and normal controls (C) fed ad libitum. On the 21st day of gestation the maternal body and liver weight, blood glucose, and plasma protein concentrations were lower in ET and PF animals as compared to C. In contrast to C or PF mothers, ET-fed mothers had higher circulating beta-hydroxybutyrate and triacyglyceride levels and beta-hydroxy-butyrate/acetoacetate ratio. Liver triacylglycerides were increased whereas liver glycogen concentration was reduced in ET-fed animals. Only fetal body and liver weights and blood glucose were lower in both ET and PF than in C. Blood beta-hydroxybutyrate was increased and liver glycogen was decreased only in ET fetuses. There were no differences among the groups in fetal circulating beta-hydroxy-butyrate/acetoacetate ratio, plasma proteins, and triacylglycerides or liver triacyglyceride content. Results indicate that certain changes in ET mothers are specifically produced by the ethanol intake rather than undernutrition. Further, metabolic changes occurring in the fetus are influenced by the ethanol effects in the mother and these actions may be added to those directly produced by the ethanol crossing the placenta. However, the collaterals were three times more likely to report more drinking days than the patients; 40.4% (86/213) of the cohabiting contacts reported more drinking days compared to 12.7% (27/213) of the patients reporting more drinking days (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

PubMed1988

Effect of postweaning thyroid status on endocrine and adipose development in rats.

We previously reported that 6 wk after thyroidectomy, rat fat cell diameter and number were 86 and 32% of values in age-matched controls. This study aims to 1) determine the time course of these changes and of parallel changes in the levels of several hormones known to participate in adipose differentiation and 2) try to normalize the altered cellularity with thyroxine (T4) treatment. Rats were thyroidectomized (T) or sham-operated and studied 2, 5, or 6 wk later. At 5 wk some T rats received L-T4. Epididymal fat cells were sized and used to estimate fat cell number. Triiodothyronine (T3), T4, thyroid-stimulating hormone, somatotropin (GH), and insulin plasma levels were assayed. In T rats fat cell hypertrophia was blunted uniformly with time, whereas fat cell hyperplasia was slow for 2 wk and zero thereafter. Insulinemia was less drastically reduced than T4, T3, and GH levels. The fat cell number-to-body weight ratio always stayed close to the ratio present at thyroidectomy. In T rats receiving a T4 substitution dose for 1 wk, fat cell number and body weight increased, but not when the T4 dose was lower even though the plasma thyroid hormone levels were increased. These thyroid hormone effects on adipose tissue are probably secondary to other endocrine changes that occur in hypothyroidism.

Adipose Tissue↗

PubMed1988

Different response to maternal hypothyroidism during the first and second half of gestation in the rat.

Female rats were mated and thyroidectomized (T) on the same day and divided into four groups. Three groups were subsequently treated daily with 1.8 micrograms L-T4/100 g body wt: 1) for the first 12 days [T + T4 (I)]; 2) from the 12th day until death [T + T4 (II)]; or 3) for the entire 21-day study [T + T4 (I + II)]. The other T animals were maintained without treatment. (T), and another group of mated rats were sham operated (C). Maternal body weight increase during gestation did not differ between T + T4 (I + II) and C dams, whereas it was smaller in T dams from the 7th gestational day onward. Neither interruption of T4 treatment in the T + T4 (I) rats after the 12th day nor treatment initiated at that time in the T + T4 (II) group modified their body weights. At day 21, the weights of the maternal conceptus-free body and liver, the placenta, and the fetuses were lower in the T and T + T4 (II) animals than in either the C and the T + T4 (I + II) animals. Maternal plasma T4 and pituitary GH content were reduced, and plasma TSH was enhanced in both T and T + T4 (I) dams. In fetuses, plasma TSH concentration was augmented in T and T + T4 (I) rats and unchanged in T + T4 (II) animals when compared with those of T + T4 (I + II). Pituitary GH content was reduced in T and T + T4 (II) fetuses and unchanged in the T + T4 (I) group. We propose that maternal thyroidectomy greatly decreases the thyroid hormone levels in embryonic structures during the first half of gestation and inhibits normal maternal metabolic changes during this period. In addition to interfering with normal fetal development, these effects reduce the quantity of maternal substrates available to fetuses during the last phase of gestation. In contrast, when maternal hypothyroidism occurs during the second half of gestation, the effects are not as detrimental because fetal thyroid gland activity is adequate, and maternal catabolic adaptations are not impaired.

Adaptation, Physiological↗