Several authors have shown that secondary hypothyroidism was programed by neonatal thyroxine (T4) treatment. However, the associated changes of body weight (BW) were less studied, especially those related to the body fat proportion. Here, we have evaluated the effect of neonatal thyroxine treatment on BW, fat proportion, serum leptin, and thyroid function of 60-day-old rats. Wistar rats were treated with thyroxine (50 microg/100 g BW, ip) (T) or saline (S), during the first 10 days of life. BW, nose-rump length (NRL), and food consumption were monitored for 60 days, when the animals were sacrificed. Thyroid function was evaluated by thyroid radioiodine uptake (RAIU), serum T3, T4, TSH, and liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD) and type 1 and 2 deiodinases (D1 and D2) activities, which are thyroid hormone-dependent enzymes. T animals showed lower food intake, BW and NRL, but higher total fat mass (+33%) and serum leptin (+46%). They also showed lower serum T3 (-23%), T4 (-32%), TSH (-36%), RAIU (-29%) and mGPD activity (-22%). Hypothalamic and pituitary D2 activities were higher (+24% and 1.4 fold, respectively), while brown adipose tissue (BAT) D2 and skeletal muscle D1 activities were lower (-30% and -62%, respectively). Thus, neonatal hyperthyroidism programs for a higher fat proportion and hyperleptinemia, which can explain the lower food intake. The TH-dependent enzymes activities changed accordingly, except for the decrease in BAT D2, which may be due the role played by the hyperleptinemia. Finally, the decrease in peripheral deiodination may contribute to a lower me-tabolic rate that may increase the adiposity.
We have shown that protein restriction during lactation is associated with higher levels of serum and milk tri-iodothyronine (T 3 ) with lower serum thyroxine (T 4 ), suggesting an increased T 4 to T 3 conversion. To investigate this hypothesis, the activity of type 1 (D1) and/or type 2 (D2) iodothyronine deiodinases was evaluated on days 4, 12 and 21 of lactation in several tissues of dams fed an 8% protein-restricted (PR) diet and controls fed a 23% protein diet. Serum TSH, T 3 and T 4 were measured by radioimmunoassay. Deiodinase activity was determined by the release of 125 I from 125 I-reverse T 3 , under specific conditions for D1 or D2. PR dams had a transitory reduction in liver D1 activity (P<0·05) on day 12, and a small increase in thyroid D1 on day 12 followed by a small decrease on day 21. However, thyroid D2 activity was higher than controls (P<0·05) during the whole of the lactation period. Mammary gland D1 and D2 activities were lower on day 4 of lactation in PR dams (P<0·05), and D2 was higher on day 21 (P<0·05). Potentially, a lower conversion of T 3 to di-iodothyronine in the mammary glands of PR dams at the beginning of lactation may serve to provide more T 3 through the milk. Brown adipose tissue (BAT) D2 activity was higher (P<0·05) in PR dams during all periods of lactation. PR dams showed higher skeletal muscle D1 activity only at the end of lactation, but no changes in D2 activity. Higher pituitary D1 and D2 activities in the PR group (P<0·05) at the end of lactation could have contributed to the lower serum TSH. These data suggest that the higher thyroid and BAT D2 activity during the whole of lactation and skeletal muscle D1 activity at the end of lactation may contribute to the higher serum T 3 in PR dams.
We report an original case of a 27-year-old transgender woman who developed lupus nephritis after male-to-female sex reassignment surgery. The patient had been taking hormones to induce feminization since the age of 18. She was admitted with malar "butterfly" rash, anasarca and hypertension, associated with an increase in serum creatinine (1.7 mg/dl). Renal involvement was characterized by nephritic and nephrotic syndrome. Autoantibody tests were positive for antinuclear antibodies and anti-double-stranded DNA, and complement levels were markedly reduced. Renal biopsy demonstrated diffuse proliferative glomerulonephritis and granular immune complexes deposits with a "full-house" pattern at the immunofluorescence level. The induction treatment was realized with corticosteroid and cyclophosphamide and maintenance immunosuppression phase with mycophenolate, obtaining complete remission. We speculated that lupus nephritis was induced by estrogens and antiandrogen therapy and gonadectomy. In the present case, we discuss the role of sex hormones in systemic lupus erythematosus onset and review the cases linked to transgender patients.
IntroductionThe peripheral metabolism of thyroxin (T 4 ) to triiodothyronine (T 3 ) is catalyzed by two isoenzymes known as type 1 (D1) and type 2 (D2) iodothyronine deiodinase. D1 is predominantly found in liver, kidney and thyroid, and seems to play a major role in the serum T 3 pool. D2 is most expressed in pituitary, brain and brown adipose tissue, where it appears to catalyze local T 3 generation and also contributes to circulating T 3 levels. TSH is an important positive regulator of thyroid deiodinase activity and expression. In peripheral tissues, including liver, D1 is stimulated by circulating thyroid hormones. In hyperthyroidism, an increase in D1 activity and a reduction in D2 activity occurs, with the reverse applying in hypothyroidism; the opposite effect was observed in the deiodination profile [1].Nutritional status and hormonal regulation have been shown to affect development during critical periods earlier in life, which could permanently program the structure and physiology of the body's tissues and systems [2]. During neonatal period, we observed that leptin could program body weight and food intake to a higher level in rat adulthood [3]. Additionally, mother's nutrition during lactation could determine body weight [4] and thyroid function [5] of their offspring in adult life. Adult rats whose mothers had received protein-restriction during lactation had higher thyroid iodine uptake and serum thyroid hormones, while animals whose mothers were subjected to energy restriction only had higher serum T 3 [5]. We suggested that this could be due to a higher deiodination of T 4. So, we analyzed proteinand energy-restricted diet effects during lactation on thyroid D1 and D2 activities and liver D1 activity in 180 days-old animals to identify whether the mother's nutritional condition during lactation could influence deiodinase activity in their offspring in adult life. Material and MethodsWistar rats were kept in a room with controlled temperature (25 1 8C) and lighting (lights on from 7 a. m. to 7 p. m.). After mating, each female was placed in an individual cage with free access to water and food until delivery. Three dams were randomly assigned to each one of the following groups: control group with free access to a standard laboratory diet (23 % protein), protein-restricted (PR) group with free access to an isoenergetic low-protein diet (8 % protein), and an energy-restricted diet (ER) group receiving a standard laboratory diet in restricted quantities. These were calculated according to the mean ingestion of the PR group [4,5].Malnutrition was started at birth and ended at weaning (21 days), when rats received a normal diet until they were 180 days old. At this time, two randomly assigned animals from each of the nine litters were killed with a lethal dose of pentobarbital and blood was obtained by cardiac puncture. Thyroid and liver were excised and kept at -70 8C.Deiodinase activities were measured based on methods previously described [6] by the release of 125 I from 125 l-reverse T 3 in thyro...
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