Sex-Related Differences in Outer Ring Monodeiodination of Thyroxine and 3,3′,5′-Triiodothyronine by Rat Liver Homogenates*

Harris, Arthur R. C.; Vagenakis, Apostolos G.; Braverman, Lewis E.

doi:10.1210/endo-104-3-645

Cited by 37 publications

(34 citation statements)

References 33 publications

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“…Interestingly, we observed that the low basal liver D1 mRNA expression and enzyme activity was more pronounced in male than in female TRb K/K mice, while no sex difference was observed in WT mice. Although sex differences in liver D1 mRNA and activity have been described in rats (Harris et al 1979, Miyashita et al 1995 and mice (Riese et al 2006), we only observed a sex difference in TRb K/K and not in WT mice. Furthermore, no discrepancy was observed between D1 mRNA expression and D1 enzyme activity as described previously by Riese et al (2006), which could be due to the different genetic background of the mice.…”

Section: Discussioncontrasting

confidence: 85%

Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

Kwakkel

Chassande

Beeren³

et al. 2008

Journal of Endocrinology

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The downregulation of liver deiodinase type 1 (D1) is supposed to be one of the mechanisms behind the decrease in serum tri-iodothyronine (T 3 ) observed during non-thyroidal illness (NTI). Liver D1 mRNA expression is positively regulated by T 3 , mainly via the thyroid hormone receptor (TR)b1. One might thus expect that lacking the TRb gene would result in diminished downregulation of liver D1 expression and a smaller decrease in serum T 3 during illness. In this study, we used TRb K/K mice to evaluate the role of TRb in lipopolysaccharide (LPS, a bacterial endotoxin)-induced changes in thyroid hormone metabolism. Our results show that the LPS-induced serum T 3 and thyroxine and liver D1 decrease takes place despite the absence of TRb. Furthermore, we observed basal differences in liver D1 mRNA and activity between TRb K/K and wild-type mice and TRb K/K males and females, which did not result in differences in serum T 3 . Serum T 3 decreased rapidly after LPS administration, followed by decreased liver D1, indicating that the contribution of liver D1 during NTI may be limited with respect to decreased serum T 3 levels. Muscle D2 mRNA did not compensate for the low basal liver D1 observed in TRb K/K mice and increased in response to LPS in TRband WT mice. Other (TRb independent) mechanisms like decreased thyroidal secretion and decreased binding to thyroid hormone-binding proteins probably play a role in the early decrease in serum T 3 observed in this study.

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Section: Discussioncontrasting

confidence: 85%

Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

Kwakkel

Chassande

Beeren³

et al. 2008

Journal of Endocrinology

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“…In orchidectomized rats, hepatic D1 activity was reduced, but could be restored to normal by the substitution of testosterone (5,6). These observations suggest that physiological concentrations of testosterone stimulate D1 activity in male rats and might provide an explanation for higher D1 activity in the liver of normal male rats than in female rats (7).…”

Section: Introductionmentioning

confidence: 77%

The effects of sex-steroid administration on the pituitary–thyroid axis in transsexuals

et al. 2006

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Objective: Estrogen and androgen administration modulate the pituitary-thyroid axis through alterations in thyroid hormone-binding globulin (TBG) metabolism, but the effects of sex steroids on extrathyroidal thyroxine (T 4 ) to triiodothyronine (T 3 ) conversion in humans are unknown. Design and methods: We studied 36 male-to-female and 14 female-to-male euthyroid transsexuals at baseline and after 4 months of hormonal treatment. Male-to-female transsexuals were treated with cyproterone acetate (CA) 100 mg/day alone (nZ10) or in combination with either oral ethinyl estradiol (or-EE) 100 mg/day (nZ14) or transdermal 17b-estradiol (td-E) 100 mg twice a week (nZ12). Femaleto-male transsexuals were treated with i.m. testosterone 250 mg twice a week. A t-test was used to test for differences within groups and ANOVAwith post hoc analysis to test for differences between the groups. Results: Or-EE increased TBG (100G12%, P!0.001) and testosterone decreased TBG (K14G4%, PZ0.01), but free T 4 did not change. Td-E and CA did not affect TBG concentrations. TSH was not different between groups at baseline or after treatment. CA decreased T 3 /T 4 ratios (K9G3%, PZ0

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“…It has been reported that estradiol administered to ovariectomized (OVX) rats increased serum T3 and decreased serum T4 (1) in a dose-dependent manner. The hepatic T3 generation has been shown to be increased in ovariectomized rats treated with higher but not lower doses of estradiol (2). These data suggest that estrogen stimulates the peripheral T4 to T3 conversion by increasing the hepatic 5'-ID-I.…”

mentioning

confidence: 75%

“…Data from some studies have suggested that sex steroid hormones may modulate the 5'-iodothyronine deiodinases (5'-ID) (1)(2)(3), enzymes responsible for converting thyroxine (T4) to triiodothyronine (T3), the biologically active hormone (4). Based on several functional criteria, 5'-deiodinases are classified into two isoenzymes: type I (5'-ID-I) and type II (5'-ID-II).…”

mentioning

confidence: 99%

Effects of estradiol benzoate on 5'-iodothyronine deiodinase activities in female rat anterior pituitary gland, liver and thyroid gland

Lisboa

Curty

Moreira

et al. 1997

Braz J Med Biol Res

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There is little information on the possible effects of estrogen on the activity of 5'-deiodinase (5'-ID), an enzyme responsible for the generation of T3, the biologically active thyroid hormone. In the present study, anterior pituitary sonicates or hepatic and thyroid microsomes from ovariectomized (OVX) rats treated or not with estradiol benzoate (EB, 0.7 or 14 µg/100 g body weight, sc, for 10 days) were assayed for type I 5'-ID (5'-ID-I) and type II 5'-ID (5'-ID-II, only in pituitary) activities. The 5'-ID activity was evaluated by the release of 125 I from deiodinated 125 I rT3, using specific assay conditions for type I or type II. Serum TSH and free T3 and free T4 were measured by radioimmunoassay. OVX alone induced a reduction in pituitary 5'-ID-I (control = 723.7 ± 67.9 vs OVX = 413.9 ± 26.9; P<0.05), while the EB-treated OVX group showed activity similar to that of the normal group. Thyroid 5'-ID-I showed the same pattern of changes, but these changes were not statistically significant. Pituitary and hepatic 5'-ID-II did not show major alterations. The treatment with the higher EB dose (14 µg), contrary to the results obtained with the lower dose, had no effect on the reduced pituitary 5'-ID-I of OVX rats. However, it induced an important increment of 5'-ID-I in the thyroid gland (0.8 times higher than that of the normal group: control = 131.9 ± 23.7 vs OVX + EB 14 µg = 248.0 ± 31.2; P<0.05), which is associated with increased serum TSH (0.6-fold vs OVX, P<0.05) but normal serum free T3 and free T4. The data suggest that estrogen is a physiological stimulator of anterior pituitary 5'-ID-I and a potent stimulator of the thyroid enzyme when employed at high doses.

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Sex-Related Differences in Outer Ring Monodeiodination of Thyroxine and 3,3′,5′-Triiodothyronine by Rat Liver Homogenates*

Cited by 37 publications

References 33 publications

Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

Lacking thyroid hormone receptor β gene does not influence alterations in peripheral thyroid hormone metabolism during acute illness

The effects of sex-steroid administration on the pituitary–thyroid axis in transsexuals

Effects of estradiol benzoate on 5'-iodothyronine deiodinase activities in female rat anterior pituitary gland, liver and thyroid gland

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