Monodeiodinase Activity Research Articles

Leptin and Thyroid Hormone Regulate Hepatic Lipid Trafficking into Macro‐ and Microvesicular Pools

Ultrastructural analysis of lipid vesicle populations by TEM and light microscopy show lipid trafficking patterns in normal and obese mice (C57BL/6J lep ob) treated for 9 days with combinations of leptin, thyroid hormone (T3), iopanoic acid (reduces thyroxine deiodination), and 6-Hydroxydopamine (blocks peripheral sympathetic neurons). Hepatic lipids selectively traffick into the VLDL export pathways in response to hormones that characterize a well-fed nutritional status (leptin and T3) but are diverted to a distinct microvesicular pool with hypernutrition (elevated T3). Endocrine profiles associated with hyponutrition (low 5′Monodeiodinase activity, decreased T3, leptin deficiency) promote macrovesicular storage due to reduced VLDL export and/or reduced adrenergic receptor-mediated macrovesicle breakdown. In the case of nonalcoholic fatty liver disease (NAFLD), it is likely that the bottlenecking of VLDLs at the site of export leads to excess microvesicular storage or, alternatively, a reduction in macrovesicular breakdown for VLDL export. We propose an integrated model of hepatic lipid trafficking in which leptin promotes mobilization of both stored and newly-synthesized lipids into the VLDL export pathway through direct and sympathetic-mediated mechanisms while T3 directly promotes lipogenesis and microvesicle formation plus indirectly retains both micro- and macrovesicles.

Annona squamosa seed extract in the regulation of hyperthyroidism and lipid-peroxidation in mice: Possible involvement of quercetin

Annona squamosa (Custard apple) seeds are generally thrown away as waste materials. The extract of these seeds was evaluated for its possible ameliorative effect in the regulation of hyperthyroidism in mouse model. Serum triiodothyronine (T(3)), thyroxine (T(4)) concentrations, hepatic glucose-6-phospatase (G-6-Pase) and 5'-mono-deiodinase (5'DI) activity were considered as the end parameters of thyroid function. Simultaneously hepatic lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activities were investigated to observe its hepatotoxic effect, if any. L-T(4) administration (0.5 mg/kg/d for 12 days, i.p.) increased the levels of serum T(3) and T(4), activity of hepatic G-6-Pase, 5'DI and LPO with a parallel decrease in SOD and CAT activities. However, simultaneous administration of the Annona seed extract (200 mg/kg) or quercetin (10 mg/kg) to T(4)-induced hyperthyroid animals for 10 days, reversed all these effects indicating their potential in the regulation of hyperthyroidism. Further, the seed extract did not increase, but decreased the hepatic LPO suggesting its safe and antiperoxidative nature. Quercetin also decreased hepatic LPO. When relative efficacy was compared with that of propyl thiouracil (PTU), a standard antithyroidic drug, experimental seed extract appeared to be more effective. Phytochemical analyses including HPLC revealed the presence of quercetin in the seed extract and the results on the effects of quercetin suggested the involvement of this phytochemical in the mediation of antithyroidal activity of Annona squamosa seed extract.

Ovarian iodide uptake and triiodothyronine generation in follicular fluid: The enigma of the thyroid ovary interaction

Since 1928, the iodine concentration in the ovary has been known to be higher than in every other organs except the thyroid. The ovarian iodide uptake varies with sexual activities, is enhanced by estrogens and a hypothyroid state and blocked by goitrogens. The recent discovery of a sodium iodide symporter (NIS) in ovaries has offered a possible mechanism for ovarian iodide uptake and other functional similarities to its thyroid counterpart. Nevertheless, the physiological significance of ovarian iodine uptake and accumulation remains unknown. The presence of thyroid hormones (TH) in follicular fluid (FF) has been established recently. Our preliminary studies on TH in FF (1996–1998) in rabbits, pigs, horses showed that the concentration of T 4 is generally lower than that in serum and that for T 3 is within the normal range or higher. A positive correlation exists between the T 4 levels in FF and serum but not between the corresponding T 3 levels. These studies revealed, for the first time, the presence of the ovarian 5′-monodeiodinase system in FF capable of generating T 3 (ovary-born T 3) by outer ring deiodination of T 4. In mares, seasonal polyestrus, ovarian 5′-monodeiodinase (MD) activity and FF T 3 levels have been found to be higher during the ovulatory period than in the anovulatory one. The exact physiological significance of this system generating T 3 and coexisting with isoforms of TH receptors in granulosa cells has not been elucidated. A direct role of T 3 for the early follicular development, differentiation and for the steroidogenic capability of granulosa cells, although strongly suggested by data obtained from in vitro studies, has to be elucidated.

Thyroid hormones (TH) and 5'-monodeiodinase (5'-MD) activity in goat's milk from the early, mid- and late lactation period.

The physiological significance of thyroid hormones (TH) present in colostrum and milk is still under consideration. The present study was aimed at determining milk thyroxine (T4) and triiodothyronine (T3) levels in three lactation phases (early, mid- and late) of the goat, and to measure activity of the milk 5'-deiodinase (5'-MD) enzyme responsible for the intramammary conversion of prohormone T4 to its metabolically highly active form T3. Thirty-two milk goats (Polish White breed) fed a standard diet were used for milk sampling. The highest TH levels in mammary secretion were recorded during the first 2-3 days post partum. Then the hormone levels decreased, and by about Day 7 fluctuated around the overall mean for the early-lactation phase (Days 1 to 24 of lactation), recording 0.134+/-0.059 microg T4 and 150.8+/-2.80 ng T3 in 100 ml of the milk. Such T4 concentrations appeared to be comparable to those in the rabbit and human, whereas the concentration of T3 was higher than in the cow, pig and mare's milk. Milk 5'-MD activity was higher (P < 0.01) during early and late lactation, compared to the mid-lactation phase. It coincided with low T4 and high T3 milk levels during early lactation, and with high milk T4 and low T3 concentrations during late lactation. The quantity of T4 and T3 available to newborn kids in milk suggests that TH ingested with the colostrum may have a physiological role during the early postnatal life of suckling goats.

70-Year-Old Woman With Rash and Muscle Weakness

70-Year-Old Woman With Rash and Muscle Weakness

Seasonality in thyroid function in chalcides ocellatus (reptilia, scincidae)

To characterize seasonal changes in thyroid function in a terrestrial reptile, Chalcides ocellatus, variations in thyroid gland, in plasma levels of thyroid hormones, 3, 5, 3'triiodothyronine (T3) and thyroxine (T4), thyroid stimulating hormone (TSH), in hepatic contents of thyroid hormones, and 5'‐T4 (ORD) (type II) monodeiodinase activity were measured over a period of two years. Morphologically, the thyroid gland exhibited distinct cycles, with a reduction of activity in November, a complete stop in December‐January (low follicular epithelium, colloid compact and devoid of reabsorption vacuoles), a fair secretory activity in March‐April and a maximum of activity in June‐July (follicular epithelium very high and colloid retracted, with clear signs of reabsorption). At the same time, plasma levels of T3 and T4 were low in winter but increased in March, reaching maximal levels in July. A low hepatic content of thyroid hormones was found during the winter, but it increased rapidly after spring to maximal values in July. Besides, the maximal activity of the hepatic 5'‐T4 ORD (type II) monodeiodinase was recorded in July, while minimal activity was present in winter. Plasma TSH levels were high between March and July and were low from November to January.

A study of iodothyronine 5′-monodeiodinase activities in normal and pathological tissues in man and their comparison with activities in rat tissues

The present study was undertaken to investigate the peripheral iodothyronine 5′-monodeiodination in different human and rat tissues. We studied iodothyronine 5′-monodeiodinase type I (5′-DI) activity in liver, kidney, intestine, right cardiac atrium and skeletal muscle and we compared the results with those in rat tissues. Iodothyronine 5′- monodeiodinase type II (5′-DII) activity was studied in normal and ischemic human heart and in rat normal myocardium and brain. The 5′-DI activity (fmol/min·mg protein) in liver and kidney was significantly higher (p<0.001, ANOVA) in normal rat tissue than in human. However, no significant differences were observed in 5′-DI activity between normal and tumoral human intestine or between intestinal tissue of man and rat. 5′-DI activity in normal human skeletal muscle was significantly higher than that in rat skeletal muscle (p<0.05). The 5′-DI activity was lower in human ischemic myocardium when compared to normal myocardium either in humans (p<0.05) or rat (p<0.001). The Km of 5′-DI was significantly lower in rat than in human kidney and liver (p<0.05). We conclude that 1) 5′-DI is distributed widely among extrathyroidal human and rat tissues and 5′-DII activity is detectable both in human and rat heart; 2) 5′-DI activity in liver and kidney is lower in man than in rat; 3) 5′-DI activity in the skeletal muscle is higher in man than in the rat; 4) 5′-DI activity is decreased in tumoral tissues of human liver and kidney and in ischemic myocardium, while no significant difference was found between human and rat cardiac 5′-DII activity.

Type II and type III monodeiodinase activities in the skin of untreated and propylthiouracil-treated cashmere goats

The presence or absence of types I, II and III iodothyronine monodeiodinase enzymes (MDI, MDII and MDIII) and their levels of activity in the skin of goats, which were orally dosed for 60 days with 0, 1.1, 2.2, 4.4, 8.8, 17.5, or 35 mg–1kg liveweight day–1of the anti-thyroid, enzyme-inhibiting drug, propylthiouracil (PTU), were determined. Contrary to our earlier report that PTU did not influence skin MDII activity, the currect more thorough investigation (in terms of numbers of observations and the efficiency of the enzyme extraction procedure) indicated that doses of 1.1.to 17.5 mg kg–1liveweight induced a 2 to 3 fold increase (P = 0.01) in MDII activity. However, in three of the four goats treated with 35 mg kg–1group, activity was similar to that of control animals. There were no significant differences between treatments in MDIII activity but there was a trend towards lower levels of activity in the goats dosed with 17.5 and 35 mg kg–1. It is concluded that there is significant MDII and MDIII activity in the skin of goats and that although there is none of the PTU -sensitive MDI enzyme, synthesis of T3 within the skin could nevertheless be modified through increases in MDII activity induced by lower T4 concentrations in the circulation caused byPTU . Changes in pattern of fibre moult induced by treatment with low doses of MD-inhibiting drugs may therefore be achieved through this effect. Since MDII and MDIII enzyme activity may be reduced by high doses of PTU, prolonged treatment with high doses of PTU may have adverse effects on skin tissue.

Evaluation of thyroid hormone economy in elasmobranch fishes, with measurements of hepatic 5?-monodeiodinase activity in wild dogfish

This paper reviews the current understanding of thyroid hormone economy and homeostasis in elasmobranch fishes and considers those measures of the activity of the hypothalamic-pituitary gland-thyroid gland-peripheral tissue axis that are necessary for adequate assessment of thyroid hormone physiology. In particular, we focus on the value of measuring hepatic 5'-monodeiodinase (5'-MDA) activity as an indicator of the animal's cellular production rate of the active thyroid hormone, triiodo-L-thyronine (T(3)). We also examine the characteristics of hepatic 5'-MDA activity, in vitro, in adult female dogfish (Squalus acanthias) collected from Passamaquoddy Bay, New Brunswick, Canada, and in the embryos that they were carrying. T(3) production from T(4) by hepatic homogenates in vitro was time- and temperature-dependent, and was enhanced by the presence of a thiol donor. Michaelis constant (K(m)) and maximum reaction velocity (V(max)) values were 3.8 x 10(-7) M and 0.29 nM T(3)/mg protein/hr, respectively. The inclusion of trimethylamine-N-oxide (TMAO) or a mixture of urea, TMAO, betaine and sarcosine significantly enhanced T(3) production. Hepatic 5'-MDA activity was depressed in fish fasted for 7 days. J. Exp. Zool. 284:492-499, 1999.

Evaluation of thyroid hormone economy in elasmobranch fishes, with measurements of hepatic 5′‐monodeiodinase activity in wild dogfish

This paper reviews the current understanding of thyroid hormone economy and homeostasis in elasmobranch fishes and considers those measures of the activity of the hypothalamic-pituitary gland-thyroid gland-peripheral tissue axis that are necessary for adequate assessment of thyroid hormone physiology. In particular, we focus on the value of measuring hepatic 5′-monodeiodinase (5′-MDA) activity as an indicator of the animal's cellular production rate of the active thyroid hormone, triiodo-L-thyronine (T3). We also examine the characteristics of hepatic 5′-MDA activity, in vitro, in adult female dogfish (Squalus acanthias) collected from Passamaquoddy Bay, New Brunswick, Canada, and in the embryos that they were carrying. T3 production from T4 by hepatic homogenates in vitro was time- and temperature-dependent, and was enhanced by the presence of a thiol donor. Michaelis constant (Km) and maximum reaction velocity (Vmax) values were 3.8 × 10−7 M and 0.29 nM T3/mg protein/hr, respectively. The inclusion of trimethylamine-N-oxide (TMAO) or a mixture of urea, TMAO, betaine and sarcosine significantly enhanced T3 production. Hepatic 5′-MDA activity was depressed in fish fasted for 7 days. J. Exp. Zool. 284:492–499, 1999. © 1999 Wiley-Liss, Inc.

New insights into the mechanism and actions of growth hormone (GH) in poultry

Despite well documented anabolic effects of GH in mammals, a clear demonstration of such responses in domestic poultry is lacking. Recently, comprehensive dose-response studies of GH have been conducted in broilers during late post-hatch development (8 to 9 weeks of age). GH reduced feed intake (FI) and body weight gain in a dose-dependent manner, whereas birds pair-fed to the level of voluntary FI of GH-infused birds did not differ from controls. The reduction in voluntary FI may involve centrally mediated mechanisms, as hypothalamic neuropeptide Y protein and mRNA were reduced with GH, coincident with the maximal depression in FI. Growth of breast muscle was also reduced in a dose-dependent manner. Circulating IGF-I was not enhanced by GH, despite evidence that early events in the GH signaling pathway were intact. A GH dose-dependent increase in circulating 3,3′,5-triiodothyronine(T3) paralleled decreases in hepatic 5D-III monodeiodinase activity, whereas 5′D-I activity was not altered. This confirms that a marked hyperthyroid response to GH occurs in late posthatch chickens, resulting from a decrease in the degradative pathway of T3 metabolism. This secondary hyperthyroidism would account for the decreased skeletal muscle mass (52) and lack of enhanced IGF-I (53) in GH-treated birds. Based upon these studies, it is now evident that GH does in fact have significant effects in poultry, but metabolic responses may confound the anabolic potential of the hormone.

Effects of Polychlorinated Biphenyls on Thyroid Hormones and Liver Type I Monodeiodinase in the Chick Embryo

Polychlorinated biphenyls (PCBs) are widespread environmental contaminants which can biomagnify to higher tropic level organisms including birds. Circulating thyroid hormones (TH) and growth are decreased by PCB exposure. The first set of studies investigated the effects of PCBs on an enzyme responsible for TH homeostasis, hepatic type I monodeiodinase (MDI) in chicken embroys. Fertile chicken eggs were injected with Aroclor 1242, Aroclor 1254, 2,2′,6,6′-tetrachlorobiphenyl (TCB), 3,3′,4,4′-TCB, or 3,3′,5,5′-TCB on Day 0 and studies were terminated on Incubation Day 21. Hepatic MDI activity was reduced in embryos treated with the Aroclor mixtures. No effects on MDI activities were observed after PCB isomer treatment. Liver weights from embryos treated with Aroclor 1242 were decreased. In the second study, chick embryos were exposed to these same PCBs in order to evaluate their effect on circulating THs and growth. Treatment with PCBs had no effect on body weight. Femur length were decreased with Arcolor 1242 treatment. A decrease in plasma concentration of thyroxine was observed after treatment with Aroclor 1242 and Aroclor 1254. Based on these findings, it is evident that PCBs alter the thyroid axis. Bird circulating TH levels, which are generally reported, may not be a good biomarker for low-dose exposure to PCBs. However, the reduction in MDI activity was more sensitive to PCB mixture exposure and may be a useful biomarker.

Cadmium induced thyroid dysfunction in chicken: hepatic type I iodothyronine 5′-monodeiodinase activity and role of lipid peroxidation

Administration of cadmium chloride (2.5 mg/kg body weight/day) to chickens daily for 15 days decreased serum triiodothyronine (T 3) concentration (by 68.75%) without altering the levels of serum thyroxine (T 4). Hepatic 5′-monodeiodinase (5′D-I) and superoxide dismutase (SOD) activities were also decreased (by 90.47% and 20.81% respectively) with a concomitant increase in lipid peroxidation (LPO, by 206.25%). Administration of the antioxidant vitamin E (α-tocopherol, 5 mg/kg body weight on alternate days) to cadmium intoxicated chickens restored thyroid function by maintaining normal hepatic 5′D-I activity and serum thyroid hormone concentrations. It also prevented cadmium-induced increase in LPO. We conclude that the metal-induced inhibition in hepatic 5′D-I activity is mediated through LPO.

Changes in thyroid function tests during short-term salsalate use

Although long-term administration of salsalate depresses blood levels of both total thyroxine (T 4) and total triiodothyronine (T 3) and at least transiently decreases serum thyrotropin (TSH), changes in thyroid function tests have not been fully characterized during its short-term use. It is also unclear if the observed changes are solely the result of decreased hormone binding to carrier proteins or if reduced hepatic 5′-monodeiodinase activity is important. Blood was sampled at baseline (day 0) and after 24 hours (day 1) and 72 hours (day 3) in eight subjects taking a therapeutic dose of salsalate 1,500 mg twice daily. Total T 4 decreased from 90.1 ± 7.7 nmol/L (mean ± SD) on day 0 to 82.9 ± 8.6 nmol/L on day 1 ( P = .1 v baseline) and 68.6 ± 8.7 nmol/L on day 3 ( P = .0001). Total T 3 decreased from 1.76 ± 0.20 nmol/L to 1.61 ± 0.16 nmol/L on day 1 ( P < .05) and 1.31 ± 0.27 nmol/L on day 3 ( P = .002). The T 4 T 3 ratio was 51.7 ± 7.7 at baseline and remained unchanged after 3 days. Levels of reverse T 3 (rT 3) were reduced from 0.24 ± 0.05 nmol/L to 0.18 ± 0.02 nmol/L on day 3 ( P < .05). While the free T 4 index (FTI) declined in parallel with total T 4, the free T 4 level by direct equilibrium dialysis (FTD) was unchanged after 3 days. Serum TSH decreased from 1.47 ± 0.47 mU/L to 0.91 ± 0.27 mU/L after 1 day ( P < .05) and remained suppressed after 3 days (0.95 ± 0.49 mU/L, P < .05). In conclusion, (1) therapeutic doses of salsalate significantly decrease serum concentrations of total T 4, total T 3, and rT 3 to about 75% of baseline levels after 3 days without altering the T 4 T 3 ratio; (2) although the FTD does not change, serum TSH concentrations remain suppressed; and (3) the proportionate decrease in total thyroid hormone levels suggests that inhibition of hormone binding to serum proteins is more important in producing these changes than reduced hepatic 5′-monodeiodinase activity.

Characterization of Thyroid Hormone 5′-Monodeiodinase Activity in the Turtle (Trachemys scripta)

Thyroid hormone metabolism by 5′-monodeiodinase enzymes (5′MD) was characterized in peripheral tissues of the turtle,Trachemys scripta,and compared with activity measured in the rat. Based on differences in pH dependence, sensitivity to inhibitors, substrate affinity, and cofactor requirements, at least two types of enzyme activities have been identified in the turtle. A 5′MD activity was measured in liver and kidney microsomal fractions that exhibits inhibition by 2n-propyl-6-thiouracil (PTU), a higher affinity for rT3(Km=2 μM) than for T4(Km=6.5 μM), a low cofactor dependence, and a high pH optimum for T4metabolism. The characteristics of this turtle low affinity T4activity correspond to the mammalian type I monodeiodinase. A second type of monodeiodinase (MD) activity that is less sensitive to PTU, has a higher affinity for T4(Km=1 nM), a higher cofactor requirement, and a lower pH optimum was colocalized with the first form. Both turtle MD activities remain active over a range of temperatures, allowing for activity at the preferred body temperature of this species (28 to 37°C compared to the 37°C optimum in the rat). Based on limited comparative data of MD systems from several fish and birds, the turtle most closely resembles avian species. Like birds, turtles possess a mammalian-like type I activity and have colocalized MD forms in the liver. However, the second turtle MD form (MDH) is not comparable to the mammalian or avian MDII-like activity. Analysis of the deiodinase products from both turtle MDs by high-performance liquid chromatography confirmed that the putative turtle MDI produces T3from T4as expected. The MDH produces rT3from T4as does the mammalian type III form, but MDH has a wider tissue distribution (kidney, liver, pancreas, heart, ovary, and brain) and distinct enzyme kinetics. Moreover, MDH activity in the turtle kidney is 100-fold higher than in the liver, indicating that the kidney may play a critical role in the metabolism of thyroid hormones in the turtle; this high renal activity distinguishes the turtle from all other vertebrates studied.

Cobalt Deficiency Effects on Trace Elements, Hormones and Enzymes Involved in Energy Metabolism of Cattle

This study was conducted to investigate the physiological consequences of long-term moderate cobalt deficiency in beef cattle, which have not hitherto been studied in detail. Cobalt deficiency was induced in cattle by feeding two groups of animals either a basal corn silage-based diet that was moderately low in cobalt (83 micrograms Co/kg), or the same diet supplemented with cobalt to a total of 200 micrograms per kg, for 43 weeks. Cobalt deficiency was induced, as judged by inappetance, diminished growth gain and a markedly reduced vitamin B12 status in serum and liver. The long-term cobalt deprivation which was primarily a combination of reduced feed intake and a tissue vitamin B12 deficiency did not show evidence of a significant dysfunction of energy metabolism. The activities of glucose-6-phosphate dehydrogenase and cytochrome oxidase in liver remained unaffected by cobalt deficiency, nor was there a significant change in serum glucose level of cattle on the cobalt-deprived diet. However, analysis of thyroid hormone status indicated a slight reduction of type I thyroxine monodeiodinase activity in liver accompanied by a significant reduction of the triiodothyronine level in serum. The diminished liver vitamin B12 level resulted in significantly reduced folate level in this tissue, reduced concentrations of heme-depending blood parameters. Moreover cobalt deficiency or rather vitamin B12 deficiency was accompanied by a dramatic accumulation of the trace elements iron and nickel in liver. These results indicate that long-term moderate cobalt deficiency may induce a number of physiological changes in cattle, but a follow-up study, which excluded different feed levels by including a pair-fed control group, will be necessary to actually obtain the single effect of cobalt deficiency in cattle.

An Oxidative Mechanism for the Inhibition of Iodothyronine 5′-Monodeiodinase Activity by Lead Nitrate in the Fish, Heteropneustes fossilis

An oxidative mechanism in the lead-induced inhibition of thyroid function with special reference to iodothyronine 5′- monodeiodinase (5′-ID) activity has been identified in the fish, Heteropneustes fossilis. Lead treatment (2.5, 5.0 and 10.0 ppm of lead nitrate/day for 30 days) enhanced tissue lipid peroxidation (LPO) and decreased the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT). In addition, serum triiodothyronine (T3) concentration and hepatic 5'-ID activity were markedly decreased by 10 ppm of lead nitrate. These findings support the view that higher concentrations of lead nitrate inhibit the extrathyroidal conversion of thyroxine (T4) to T3. Moreover, oxidative stress from lead intoxication could be responsible for inhibiting 5′-ID activity.

Role of ascorbic acid in cadmium-induced thyroid dysfunction and lipid peroxidation.

A study on the effects of ascorbic acid (AA) on heavy metal (cadmium)-induced thyroid dysfunction and lipid peroxidation (LPO) was carried out in Swiss male mice. The animals were administered with either cadmium (1.0 mg kg(-1) body wt.) alone or in combination with AA (1 mM) every day for 15 days. While cadmium treatment led to a decrease in the serum concentrations of thyroid hormones and hepatic type I iodothyronine 5'-monodeiodinase (5'D-I) activity, an increase in the level of lipid peroxidation was observed. The metal-induced decrease in hepatic 5'D-I activity and serum triiodothyronine (T3) concentration was restored by treatment with AA. However, AA could not restore the serum thyroxine (T4) concentration. The increased level of LPO was also ameliorated by AA. It appears that the protective effect of AA against cadmium-induced thyroid dysfunction is mediated through its antioxidative action.

Effect of propylthiouracil-induced hypothyroidism on thyroid hormone profiles and tissue deiodinase activity in cashmere goats

The relationships between dose of propylthiouracil (PTU), circulating plasma thyroid hormone concentrations and 5′-monodeiodinase enzyme activity were investigated to determine the dose and duration of PTU treatment required to suppress plasma thyroid hormone levels in cashmere goats. Six groups of four cashmere goats were orally dosed for 2 months with between 1.1 and 35 mg/kg/bw per day of PTU. Mean thyroxine (T4) concentrations in goats treated with 1.1 mg/kg of PTU did not differ significantly from the control animals at any time during the study. However, in goats treated with 2.2 to 35 mg/kg/day of PTU, T4 concentrations declined in a dose dependent manner and plateaued after approximately 1 month of treatment. Mean plasma triiodothyronine (T3) concentrations were not significantly affected by any of the PTU doses. Type I 5′-monodeiodinase (type I 5′-MDI) activity in liver and kidney in the 1.1 mg/kg group was suppressed to 25 and 37%, respectively, of values recorded in control animals (24.3 vs. 98.4 for liver, and 15.7 vs. 42.4 pmol iodine released/h/mg protein for kidney), and was below assay sensitivity at doses of PTU>4 mg/kg. Type II 5′-monodeiodinase activity in goat skin was detected at approximately 11.5 fmol iodine released/h/mg/protein and was not apparently affected by PTU treatment. It is concluded that a dose≤1 mg/kg/bw PTU can be used in long-term studies in goats, to inhibit extrathyroidal conversion of T4 to T3 via type I 5′-MDI without influencing circulating thyroid hormone profiles.

Possible involvement of lipid peroxidation in the inhibition of type I iodothyronine 5'-monodeiodinase activity by lead in chicken liver.

The possible involvement of lipid peroxidation (LPO) in the lead-induced inhibition of type I iodothyronine 5'-monodeiodinase activity (5'-D) has been worked out in chicken liver. Lead nitrate (1.5 mg per bird per day) for 30 days increased the lipid peroxidative process with a concomitant decrease in 5'-D activity in chicken liver. Also, a significant decrease in serum triiodothyronine (T3) concentration and an increase in serum thyroxine (T4) concentration were observed. The data suggest that lead-induced inhibition of type I 5'-D activity in chicken liver is mediated through the lipid peroxidative process.