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Iodine and the Body

 

Iodine and the Breast  

ACEVES

 

Uptake and gene expression with antitumoral doses of iodine in thyroid and mammary gland: evidence that chronic administration has no harmful effects.

Anguiano B, Garcia-Solis P, Delgado G, Velasco CA.

Thyroid. 2007 Sep;17(9):851-9.

 

"Several studies have demonstrated that moderately high concentrations of molecular iodine (I(2)) diminish the symptoms of mammary fibrosis in women, reduce the occurrence of mammary cancer induced chemically in rats (50-70%), and have a clear antiproliferative and apoptotic effect in the human tumoral mammary cell line MCF-7. Nevertheless, the importance of these effects has been underestimated, in part because of the notion that exposure to excess iodine represents a potential risk to thyroid physiology. In the present work we demonstrate that uptake and metabolism of iodine differ in an organ-specific manner and also depend on the chemical form of the iodine ingested (potassium iodide vs. I(2)). Further, we show that a moderately high I(2) supplement (0.05%) causes some of the characteristics of the "acute Wolff-Chaikoff effect"; namely, it lowers expression of the sodium/iodide symporter, pendrin, thyroperoxidase (TPO), and deiodinase type 1 in thyroid gland without diminishing circulating levels of thyroid hormone. Finally, we confirm that I(2) metabolism is independent of TPO, and we demonstrate that, at the doses used here, which are potentially useful to treat mammary tumors, chronic I(2) supplement is not accompanied by any harmful secondary effects on the thyroid or general physiology. Thus, we suggest that I(2) could be considered for use in clinical trials of breast cancer therapies."

 

 

Uptake and antiproliferative effect of molecular iodine in the MCF-7 breast cancer cell line.

Arroyo-Helguera O, Anguiano B, Delgado G, Aceves C.

Endocr Relat Cancer. 2006 Dec;13(4):1147-58.

 

"This study analyzes the uptake and antiproliferative effect of two different chemical forms of iodine, iodide (I(-)) and molecular iodine (I(2)), in MCF-7 cells, which are inducible for the Na(+)/I(-) symporter (NIS) and positive for pendrin (PDS). The mouse fibroblast cell line NIH3T3 was used as control. Our results show that in MCF-7 cells, I(-) uptake is sustained and dependent on NIS, whereas I(2) uptake is transient with a maximal peak at 10 min and a final retention of 10% of total uptake. In contrast, no I(-) was taken up by NIH3T3 cells, and although I(2) was captured with the same time pattern as in MCF-7 cells, its uptake was significantly lower, and it was not retained within the cell. The uptake of I(2) is independent of NIS, PDS, Na(+), and energy, but it is saturable and dependent on protein synthesis, suggesting a facilitated diffusion system. Radioiodine was incorporated into protein and lipid fractions only with I(2) treatment. The administration of non-radiolabeled I(2) and 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid (6-iodolactone, an iodinated arachidonic acid), but not KI, significantly inhibited proliferation of MCF-7 cells. Proliferation of NIH3T3 cells was not inhibited by 20 muM I(2). In conclusion, these results demonstrate that I(2) uptake does not depend on NIS or PDS; they suggest that in mammary cancer cells, I(2) is taken up by a facilitated diffusion system and then covalently bound to lipids or proteins that, in turn, inhibit proliferation."

 

 

Is Iodine a Gatekeeper for the Mammary Gland?

Carmen Aceves, Brenda Anguiano, Guadalupe Delgado.
J Mammary Gland Biol Neoplasia. 2005 Apr;10(2):189-96. 

        

"This paper reviews evidence showing iodine as an antioxidant and antiproliferative agent contributing to the integrity of normal mammary gland. Seaweed is an important dietary component in Asian communities and a rich source of iodine in several chemical forms....In animal and human studies, molecular iodine (I2) supplementation exerts a suppressive effect on the development and size of both benign and cancer neoplasias. This effect is accompanied by a significant reduction in cellular lipoperoxidation. Iodine, in addition to its incorporation into thyroid hormones, is bound into antiproliferative iodolipids in the thyroid called iodolactones, which may also play a role in the proliferative control of mammary gland. An I2 supplement should be considered as an adjuvant in breast cancer therapy."

 

 

Deiodinase type 1 activity is expressed in the prostate of pubescent rats and is modulated by thyroid hormones, prolactin and sex hormones.

Anguiano B, Lopez A, Delgado G, Romero C, Aceves C.

J Endocrinol. 2006 Aug;190(2):363-71.

Abstract only

 

"The aim of this study was to characterize the type of 5'-deiodinase activity in the prostate of pubescent rats (7-8 weeks), to establish its distribution in the lobes (ventral, dorsolateral, and anterior), and to analyze its modulation by prolactin (PRL), testosterone, dihydrotestosterone (DHT), and 17beta-estradiol (E(2)). Our results showed that the enzymatic activity was highly susceptible to inhibition by 6-n-propyl-2-thiouracil and gold thioglucose, its preferential substrate was reverse tri-iodothyronine (rT(3)), it exhibited a low dithiothreitol requirement (5 mM), and the apparent K(m) and V(max) values for substrate (rT(3)) were approximately 0.25 microM and 9.0 pmol liberated/mg protein per hour, respectively. All these characteristics indicate the preferential expression of type 1 deiodinase (D1), which was corroborated by demonstrating the presence of D1 mRNA in prostate. D1 activity was detected in all lobes and was most abundant in the dorsolateral. Although we detected type 2 deiodinase (D2) mRNA expression, the D2 activity was almost undetectable. D1 activity was enhanced in animals with hyperthyroidism and hyperprolactinemia, in intact animals treated with finasteride (inhibitor of local DHT production), and in castrated animals with E(2) replacement. In contrast, activity diminished in castrated animals with testosterone replacement. Our results suggest that thyroid hormones, PRL, and E(2) exert a positive modulation on D1 activity, while testosterone and DHT exhibit an inhibitory effect. D1 activity may be associated with prostate maturation and/or function."

 

 

Regulatory role of the 3' untranslated region (3'UTR) of rat 5' deiodinase (D1). effects on messenger RNA translation and stability.

Arroyo-Helguera O, Mejia-Viggiano C, Varela-Echavarria A, Cajero-Juarez M, Aceves C.

Endocrine. 2005 Aug;27(3):219-25.

[abstract only]

 

"The previous findings that both a long and a short type 1 deiodinase (D1) mRNA are present in different tissues and that the D1 gene contains two potential polyA signals suggest that the two mRNAs result from differential polyA signal usage. In this study, we examined the properties of the two D1 mRNAs generated in HEK 293 cells by the alternative use of each of the poly A signals in order to ascertain the potential regulatory role of the 3'UTR of this gene. Our results showed that the long mRNA is less stable, but that it is translated more efficiently than the short mRNA. The net result of these differences is a higher D1 activity with the long message. These data suggest that the D1 3'UTR may play an important role in regulating the stability and translational efficiency of the D1 mRNA, both of which could be physiologically relevant when the demand for D1 activity is high."

 

 

Has the mammary gland a protective mechanism against overexposure to triiodothyronine during the peripartum period? The prolactin pulse down-regulates mammary type I deiodinase responsiveness to norepinephrine.

Anguiano B, Rojas-Huidobro R, Delgado G, Aceves C.

J Endocrinol. 2004 Nov;183(2):267-77.

 

"Peripartum is a crucial period for mammary gland final differentiation and the onset of lactation. Although the 'trigger' for lactogenesis depends on several hormones, a key factor is the peripartum prolactin (PRL) pulse whose deletion results in a failure to initiate milk production. Other hormones having a critical role during this period but exerting a contrary effect are the thyronines. A transitory hypothyroidism occurs at peripartum in serum and several other extrathyroidal tissues, whereas the induction of hyperthyroidism during late pregnancy is associated with the absence of lactation after delivery. We analyzed the mammary gland during pregnancy and lactation for: (a) the type and amount of thyroid receptors (TRs), (b) the local triiodothyronine (T3) generation catalyzed by type I deiodinase (Dio1), (c) the Dio1 response to norepinephrine (NE) and (d) the effect on Dio1 and TRs of blocking the PRL pulse at peripartum. Our data showed that during pregnancy the mammary gland contains Dio1 in low amounts associated with the highest expression of TRalpha1; whereas during lactation the gland shows high levels of both Dio1 and TRalpha1. However, at peripartum, both TRs and Dio1 decrease, and Dio1 becomes refractory to NE. This refractoriness disappears when the PRL pulse is blocked by the dopamine agonist bromocriptine. This blockade is also accompanied by a significant decrease in cyclin D1 expression. Our data suggested that the peripartum PRL pulse is part of a protective mechanism against precocious differentiation and/or premature involution of the alveolar epithelium due to T3 overexposure."

 

 

Periodontal 5'-deiodination on forced-induced root resorption--the protective effect of thyroid hormone administration.

Vazquez-Landaverde LA, Rojas-Huidobro R, Alonso Gallegos-Corona M, Aceves C.

Eur J Orthod. 2002 Aug;24(4):363-9.

 

"The present investigation was designed to study the protective effect given by thyroid hormone (TH) on root resorption: (1) whether intra-peritoneal versus oral TH administration had the same efficiency; and (2) whether this effect involved local or systemic mechanisms. For this purpose, circulating T3 levels, systemic alkaline phosphatase (APase) activity, and 5'deiodinase (5'D) activity were evaluated in the periodontal area of 80 Sprague-Dawley rats, 8 weeks of age, in which orthodontic appliances had been inserted. The results showed that TH-treated animals (intra-peritoneal or oral) had significantly less force-induced root resorptive lesions compared with a control group, without apparent changes in T3 or APase levels, and that periodontal remodelling was accompanied by a significant increase in local T3 generation as a result of T4 deiodination. This 5'D activity was higher in those animals that received exogenous TH. These results suggest that this protective TH mechanism may be achieved at a local level and that administration of low doses of TH may play a protective role on the root surface either during orthodontic treatment or in those patients that present spontaneous root resorptive lesions."

 

See also articles with Garcia-Solis

 
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