Thyroid hormone: sex-dependent role in nervous system regulation and disease

Abstract

Thyroid hormone (TH) regulates many functions including metabolism, cell differentiation, and nervous system development. Alteration of thyroid hormone level in the body can lead to nervous system-related problems linked to cognition, visual attention, visual processing, motor skills, language, and memory skills. TH has also been associated with neuropsychiatric disorders including schizophrenia, bipolar disorder, anxiety, and depression. Males and females display sex-specific differences in neuronal signaling. Steroid hormones including testosterone and estrogen are considered to be the prime regulators for programing the neuronal signaling in a male- and female-specific manner. However, other than steroid hormones, TH could also be one of the key signaling molecules to regulate different brain signaling in a male- and female-specific manner. Thyroid-related diseases and neurological diseases show sex-specific incidence; however, the molecular mechanisms behind this are not clear. Hence, it will be very beneficial to understand how TH acts in male and female brains and what are the critical genes and signaling networks. In this review, we have highlighted the role of TH in nervous system regulation and disease outcome and given special emphasis on its sex-specific role in male and female brains. A network model is also presented that provides critical information on TH-regulated genes, signaling, and disease.

Sex Dimorphic Responses of the Hypothalamus-Pituitary-Thyroid Axis to Energy Demands and Stress

“…Thyroid deficiency during development affects the adequate development of brain which, depending on the stage of development, may induce several diseases as for example affect neural circuitry and cause autism observed more in boys. Neuropsychiatric disorders that are related to thyroid disfunction (more frequently affected in women) coincide with their higher incidence, for example, TH or TSH serum levels associate with Alzheimer disease in women ( 85 ). Subclinical hypothyroidism has been related with psychiatric disorders such as anxiety and depression ( 85 ).…”

“…Neuropsychiatric disorders that are related to thyroid disfunction (more frequently affected in women) coincide with their higher incidence, for example, TH or TSH serum levels associate with Alzheimer disease in women ( 85 ). Subclinical hypothyroidism has been related with psychiatric disorders such as anxiety and depression ( 85 ). Few studies have associated sex differences in depressive patients with subclinical hypothyroidism; however, a recent study reports its prevalence in women with depression being approximately two times higher than in men ( 86 ).…”

A Correlational Analysis of Phthalate Exposure and Thyroid Hormone Levels in Common Bottlenose Dolphins (Tursiops truncatus) from Sarasota Bay, Florida (2010–2019)

“…In fact, Weng et al (2017) reported similar results to this study, where MEHP was positively associated with FT4 in girls, but was not associated with T3 or T4. Disrupted thyroid function appears to be more prevalent in women compared to men [ 61 ], potentially related to the sex-specific regulation of thyroid hormones in the brain [ 62 ]. Still, significant associations between MEHP and FT4 have been demonstrated in adult male humans [ 16 ].…”

Review of construction methods for whole-cell computational models

“…SBGN has been widely used in biological system networks and provides a new method for the analysis and visualization of biological networks [73][74][75][76]. For example, the network diagram of metabolic pathways meeting the SBGN standard [77,78] and the molecular interaction diagram [79,80] have been constructed. In addition, the metabolic pathways in the KEGG database can be automatically converted into the SBGN format for visualization, while preserving as much as possible, the layout of important elements that may change as a result of model conversion [81].…”