Effect of hypothyroidism on the expression of nuclear receptors and their co-regulators in mammary gland during lactation in the rat

Arboccó, Fiorella Campo Verde; Sasso, Corina Verónica; Nasif, Daniela; Hapon, María Belén; Jahn, Graciela A.

doi:10.1016/j.mce.2015.05.026

Cited by 20 publications

(8 citation statements)

References 57 publications

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“…Key factors regulating social behaviors are oxytocin (OXT) and arginine vasopressin (AVP) and they have been studied extensively using different animal models Bielsky et al 2005;Choleris et al 2003;Crawley et al 2007;Ferguson et al 2000;Yu et al 2016) (Champagne et al 2001;Pedersen 1997;Pedersen et al 2006) (Bosch & Neumann 2012;Calcagnoli et al 2014a;Calcagnoli et al 2014b;Ferris & Potegal 1988;Pagani et al 2015). In addition, several studies have shown that thyroid hormones are also implicated in the regulation of those neuropeptides and their signaling Adan et al 1993;Burbach et al 1993;Campo Verde Arbocco et al 2015;Ciosek & Drobnik 2004;Dellovade et al 1999;Faustino et al 2015;Vasudevan et al 2001a;Vasudevan et al 2001b). Thus, it is possible that alterations in the determinants of brain thyroid hormone action contribute to social behaviors.…”

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confidence: 99%

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Stohn

Martı́nez

Zafer

et al. 2017

Genes Brain and Behavior

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Thyroid hormones regulate many aspects of brain development and function, and alterations in the levels of thyroid hormone action lead to abnormal anxiety-and depression-like behaviors. A complement of factors in the brain function independently of circulating levels of hormone to strictly controlled local thyroid hormone signaling. A critical factor is the type 3 deiodinase (DIO3), which is located in neurons and protects the brain from excessive thyroid hormone. Here, we examined whether a local increase in brain thyroid hormone action secondary to DIO3 deficiency is of consequence for social behaviors. Although we did not observe alterations in sociability, Dio3−/− mice of both sexes exhibited a significant increase in aggression-related behaviors and mild deficits in olfactory function. In addition, 85% of Dio3−/− dams manifested no pup-retrieval behavior and increased aggression toward the newborns. The abnormal social behaviors of Dio3−/− mice were associated with sexually dimorphic alterations in the physiology of oxytocin (OXT) and arginine vasopressin (AVP), 2 neuropeptides with important roles in determining social interactions. These alterations included low adult serum levels of OXT and AVP, and an abnormal expression of Oxt, Avp and their receptors in the neonatal and adult hypothalamus. Our results demonstrate that DIO3 is essential for normal aggression and maternal behaviors, and indicate that abnormal local regulation of thyroid hormone action in the brain may contribute to the social deficits associated with neurodevelopmental disorders.

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confidence: 99%

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Stohn

Martı́nez

Zafer

et al. 2017

Genes Brain and Behavior

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“…Vermiglio et al [ 79 ], who were studying iodine deficient lactating women in Italy, speculated that there was enhanced iodide concentration capacity in the mammary gland, perhaps under the control of prolactin. In hypothyroid laboratory rats, the ability to lactate was hypothesized to decrease because of changes in mammary gland nuclear receptors and their co-regulators [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective

et al. 2016

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The Institute of Medicine recommends that lactating women ingest 290 μg iodide/d and a nursing infant, less than two years of age, 110 μg/d. The World Health Organization, United Nations Children’s Fund, and International Council for the Control of Iodine Deficiency Disorders recommend population maternal and infant urinary iodide concentrations ≥ 100 μg/L to ensure iodide sufficiency. For breast milk, researchers have proposed an iodide concentration range of 150–180 μg/L indicates iodide sufficiency for the mother and infant, however no national or international guidelines exist for breast milk iodine concentration. For the first time, a lactating woman and nursing infant biologically based model, from delivery to 90 days postpartum, was constructed to predict maternal and infant urinary iodide concentration, breast milk iodide concentration, the amount of iodide transferred in breast milk to the nursing infant each day and maternal and infant serum thyroid hormone kinetics. The maternal and infant models each consisted of three sub-models, iodide, thyroxine (T4), and triiodothyronine (T3). Using our model to simulate a maternal intake of 290 μg iodide/d, the average daily amount of iodide ingested by the nursing infant, after 4 days of life, gradually increased from 50 to 101 μg/day over 90 days postpartum. The predicted average lactating mother and infant urinary iodide concentrations were both in excess of 100 μg/L and the predicted average breast milk iodide concentration, 157 μg/L. The predicted serum thyroid hormones (T4, free T4 (fT4), and T3) in both the nursing infant and lactating mother were indicative of euthyroidism. The model was calibrated using serum thyroid hormone concentrations for lactating women from the United States and was successful in predicting serum T4 and fT4 levels (within a factor of two) for lactating women in other countries. T3 levels were adequately predicted. Infant serum thyroid hormone levels were adequately predicted for most data. For moderate iodide deficient conditions, where dietary iodide intake may range from 50 to 150 μg/d for the lactating mother, the model satisfactorily described the iodide measurements, although with some variation, in urine and breast milk. Predictions of serum thyroid hormones in moderately iodide deficient lactating women (50 μg/d) and nursing infants did not closely agree with mean reported serum thyroid hormone levels, however, predictions were usually within a factor of two. Excellent agreement between prediction and observation was obtained for a recent moderate iodide deficiency study in lactating women. Measurements included iodide levels in urine of infant and mother, iodide in breast milk, and serum thyroid hormone levels in infant and mother. A maternal iodide intake of 50 μg/d resulted in a predicted 29–32% reduction in serum T4 and fT4 in nursing infants, however the reduced serum levels of T4 and fT4 were within most of the published reference intervals for infant. This biologically based model is an important first step at integr...

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“…After birth, the mammary gland is essential for the fulfillment of lactation. These tissues differentially express TR subtypes depending on the physiological state, but it is challenging to demonstrate in vivo how TH signaling promotes a certain outcome [10, 25-27]. GC-1 allowed us to differentiate TR selective actions in vivo , from initiation of gestation until newborns are capable of living on their own at weaning.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Effect of Thyromimetic GC-1 Selective Signaling on Reproductive and Lactational Performance in the Hypothyroid Rat

et al. 2021

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Introduction: The potential of the thyroid hormone receptor β (TRβ1) selective analog GC-1 has been widely proven in animal models and humans. However, its effect on the reproductive stage of the female rat has not been evaluated. Methods: The effect of the administration of GC-1 or equimolar doses of triiodothyronine (T3) was evaluated on the reproductive performance of the hypothyroid female rat and the indirect effect on pup thyroid status, weight, and survival. Results: Hypothyroidism reduced the number of embryos implanted in the uterus, whereas T3 and GC-1 treatment in hypothyroid females reestablished the number of implanted embryos to normal. Initiation of labor was delayed by hypothyroidism, and T3 replacement treatment reinstated the normal timing of parturition. The administration of GC-1 alone to the lactating mother did not affect pup survival, weight, or thyroidal status. Conclusions: Our findings show the differential effect of thyroid hormone selective signaling during gestation and the indirect exposure of the pups; we also emphasize the plausible use of GC-1 for treatment of hypothyroid mothers during the lactation period.

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Effect of hypothyroidism on the expression of nuclear receptors and their co-regulators in mammary gland during lactation in the rat

Cited by 20 publications

References 57 publications

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective

Effect of Thyromimetic GC-1 Selective Signaling on Reproductive and Lactational Performance in the Hypothyroid Rat

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