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Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats

Molecular Neurophysiology Laboratory, Department of Neurosciences Research, National Institute of Psychiatry Ramon de la Fuente Muñiz, Calzada México-Xochimilco 101, Col. San Lorenzo Huipulco, Mexico City C.P. 14370, Mexico
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2017, 9(10), 1139;
Received: 28 August 2017 / Revised: 29 September 2017 / Accepted: 11 October 2017 / Published: 18 October 2017
(This article belongs to the Special Issue Dietary Zn and Human Health)
Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood. View Full-Text
Keywords: Zn deficiency; TRH; TSH; subclinical hypothyroidism Zn deficiency; TRH; TSH; subclinical hypothyroidism
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Alcántara-Alonso, V.; Alvarez-Salas, E.; Matamoros-Trejo, G.; De Gortari, P. Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats. Nutrients 2017, 9, 1139.

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