Hipotiroidismo congénito experimental e hiposensibilidad cerebral a las hormonas tiroideas: estudio molecular en ratas Wistar macho.

Saved in:

Bibliographic Details
Title:	Hipotiroidismo congénito experimental e hiposensibilidad cerebral a las hormonas tiroideas: estudio molecular en ratas Wistar macho.
Alternate Title:	Experimental congenital hypothyroidism and thyroid hormone hyposensitivity in the brain: A molecular study in male Wistar rats.
Authors:	Razón-Hernández C, Karla Cristina^1,2,3, Osnaya-Brizuela, Norma¹, ValenzuelaPeraza, Armando¹, Navarrete-Hernández, María Sara¹, Quirarte, Gina Lorena⁴, Barragán Mejía, Gerardo⁵, Pacheco-Rosado, Jorge⁶, Becerril-Villanueva, Enrique², Pavón-Romero, Lenin², Pérez-Sánchez, Gilberto², Sánchez-Huerta, Karla¹ ksanchezh@pediatria.gob.mx
Source:	Acta Pediatrica de Mexico. 2026 Supplement, Vol. 47, pS8-S9. 2p.
Subjects:	CONGENITAL hypothyroidism, THYROID hormone receptors, NEURAL development, THYROID hormones, LABORATORY rats, MOLECULAR biology
Abstract (English):	BACKGROUND: Congenital hypothyroidism (CH) is caused by abnormalities in the development or function of the thyroid gland, leading to perinatal thyroid hormone (TH) deficiency. Clinical evidence suggests that CH induces thyroid hormone hyposensitivity (THH), a condition that results in reduced biological activity of TH due to defects in their transport, metabolism, or action mechanism. THH may provide a possible explanation for the persistent neuropsychological deficits in children who are treated with levothyroxine. However, this condition has not been demonstrated at the molecular level in rodents or humans with CH. OBJECTIVE: To determine whether experimental CH induces cerebral molecular alterations associated with a state of THH. MATERIALS AND METHODS: The effects of moderate and severe CH on the mRNA expression of thyroid transporters (Mct8 and Oatp1c1), deiodinases (DIO2 and DIO3), and receptors (TRα, TRβ, and RXRA) in the cortex, cerebellum, and hippocampus of male Wistar offspring were evaluated. Concurrently, the physical and sensorimotor development of the offspring was also monitored. RESULTS: Moderate CH reduced TRβ mRNA expression in the cerebral cortex. In addition, it caused an earlier onset of the negative geotaxis reflex and ear unfolding. However, eye opening and auditory startle were delayed. Severe HC decreased the expression of TRβ and Oatp1c1 mRNA, and delayed the fall avoidance reflex, eye opening, and auditory startle. CONCLUSION: Experimental CH decreases the cortical expression of TRβ and Oatp1c1 depending on the severity of hypothyroidism. These molecular changes partially underlie the sensorimotor developmental alterations observed in the offspring. Finally, the findings suggest that CH induces a state of THH in the cerebral cortex because of impaired TH transport across the blood–brain barrier and reduced sensitivity mediated by TRβ deficiency. [ABSTRACT FROM AUTHOR]
Abstract (Spanish):	ANTECEDENTES: El hipotiroidismo congénito (HC) ocurre por anomalías en la formación o funcionamiento de la glándula tiroides, provocando deficiencia perinatal de hormonas tiroideas (HTs). La evidencia clínica sugiere que el HC induce hiposensibilidad a las HTs (HHT), una condición que provoca actividad biológica tiroidea reducida debido a defectos en el transporte, metabolismo o mecanismo de acción hormonal. La HHT podría explicar los déficits neuropsicológicos persistentes en niños con HC tratados con levotiroxina. No obstante, esta condición no se ha demostrado a nivel molecular en roedores ni humanos con HC. OBJETIVO: Determinar si el HC experimental induce cambios moleculares cerebrales vinculados a un estado de HHT. MATERIAL Y MÉTODOS: Se evaluó el impacto del HC (moderado y severo) en la expresión del ARNm de transportadores tiroideos (Mct8, Oatp1c1), desyodasas (DIO2, DIO3) y receptores (TRα, TRβ, RXRA) en corteza, cerebelo e hipocampo de crías macho Wistar. Paralelamente, se monitoreó el desarrollo físico y sensoriomotor de las crías. RESULTADOS: El HC moderado redujo la expresión del ARNm de TRβ en la corteza cerebral. Además, provocó un adelanto en la aparición del reflejo de geotaxis negativa y en el despliegue de las orejas, pero un retraso en la apertura ocular y el sobresalto auditivo. El HC severo disminuyó la expresión del ARNm de TRβ y Oatp1c1, y provocó un retraso en el reflejo de evitación a la caída, la apertura ocular y el sobresalto auditivo. CONCLUSIÓN: El HC experimental disminuye la expresión cortical de TRβ y Oatp1c1 dependiendo de la severidad del hipotiroidismo. Estos cambios moleculares sustentan parcialmente las alteraciones del desarrollo sensoriomotor observadas en las crías. Finalmente, los hallazgos sugieren que el HC provoca un estado de HHT en la corteza cerebral debido a fallas en el transporte de HTs en la barrera hematoencefálica y a una menor sensibilidad mediada por la deficiencia de TRβ. [ABSTRACT FROM AUTHOR]
	Copyright of Acta Pediatrica de Mexico is the property of Instituto Nacional de Pediatria (INP) and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database:	MedicLatina

Description
Abstract:	BACKGROUND: Congenital hypothyroidism (CH) is caused by abnormalities in the development or function of the thyroid gland, leading to perinatal thyroid hormone (TH) deficiency. Clinical evidence suggests that CH induces thyroid hormone hyposensitivity (THH), a condition that results in reduced biological activity of TH due to defects in their transport, metabolism, or action mechanism. THH may provide a possible explanation for the persistent neuropsychological deficits in children who are treated with levothyroxine. However, this condition has not been demonstrated at the molecular level in rodents or humans with CH. OBJECTIVE: To determine whether experimental CH induces cerebral molecular alterations associated with a state of THH. MATERIALS AND METHODS: The effects of moderate and severe CH on the mRNA expression of thyroid transporters (Mct8 and Oatp1c1), deiodinases (DIO2 and DIO3), and receptors (TRα, TRβ, and RXRA) in the cortex, cerebellum, and hippocampus of male Wistar offspring were evaluated. Concurrently, the physical and sensorimotor development of the offspring was also monitored. RESULTS: Moderate CH reduced TRβ mRNA expression in the cerebral cortex. In addition, it caused an earlier onset of the negative geotaxis reflex and ear unfolding. However, eye opening and auditory startle were delayed. Severe HC decreased the expression of TRβ and Oatp1c1 mRNA, and delayed the fall avoidance reflex, eye opening, and auditory startle. CONCLUSION: Experimental CH decreases the cortical expression of TRβ and Oatp1c1 depending on the severity of hypothyroidism. These molecular changes partially underlie the sensorimotor developmental alterations observed in the offspring. Finally, the findings suggest that CH induces a state of THH in the cerebral cortex because of impaired TH transport across the blood–brain barrier and reduced sensitivity mediated by TRβ deficiency. [ABSTRACT FROM AUTHOR]
ISSN:	01862391
DOI:	10.18233/apm.v47i1S.3441