madman
Super Moderator
Abstract
Thyroid hormone (TH) regulates many functions including metabolism, cell differentiation, and nervous system development. Alteration of thyroid hormone levels 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 programming 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.
Introduction
The thyroid gland is one of the earliest endocrine organs that can be observed at twenty paired somites stage in a developing human embryo [1]. Thyroid hormones (THs) are first detected in the human fetal circulation at 11–13 gestation weeks [2]. The thyroid is the only endocrine gland that can produce and store thyroid hormones (THs), triiodothyronine (T3), and thyroxine (T4). T4 is the major TH secreted by the thyroid gland, whereas T3 is the main biologically active form. TH plays a crucial role in regulating different aspects of animal physiology. The major role played by TH is the regulation of metabolism, cellular growth, and development [3, 4]. However, recent advances in medical and molecular fields have helped to further dissect its other important role and mechanisms of action. TH has been shown to regulate nervous system differentiation as it influences neurogenesis, neuronal migration, neuronal and glial differentiation, myelination, and synaptogenesis [5–8]. Insufficiency in TH can lead to problems in cognition, visual attention, visual processing, motor skills, language, and memory skills [9]. TH is also implicated in neuropsychiatric disorders such as schizophrenia, bipolar disorder, anxiety, and depression [10, 11]. However, the molecular mechanisms of TH-mediated regulation of neuronal cells in these disorders are largely unknown. Some of the neurological diseases including Alzheimer’s disease (AD), Parkinson’s disease, and depression show a clear sex-specific incidence [12]. Moreover, thyroid-stimulating hormone (TSH) level has been associated with increased risk of dementia [13], and TSH level in plasma has become a routine screening test for the diagnosis of patients with suspected dementia [14]. Low and high TSH has been associated with an increased risk of developing AD in women [15]. This suggests that elucidation of TH regulation and mechanisms of action in both male and female brains could further help to understand neuronal differentiation as well as a neurological disease pathogenesis.
*TH production, transport, and mechanisms of action
*TH receptors (THRs) and distribution in the brain
*TH regulation and action in the brain
*Sex-specific effects of TH in the brain
*Thyroid hormone in neurodegenerative and psychiatric diseases
Conclusion and future perspectives
TH regulates critical biological processes including brain differentiation. TH has been shown to regulate brain differentiation, and any alteration in level could lead to various nervous system-related problems. The common neurological problems associated with TH are cognition, visual attention, visual processing, motor skills, language, and memory skills. TH shows sex-specific effects in brain cell differentiation which could lead to the differential organization of neural circuits. TH-related problems are also on the rise with females showing higher incidence. Our study suggests that there are clear sex-specific effects and regulation of TH in male and female brains. The sex-specific role of TH has started to emerge; however, critical links are missing to fully understand the molecular mechanisms. Understanding TH sex-specific effects could further help to advance the diagnostic as well as the therapeutic field.
Thyroid hormone (TH) regulates many functions including metabolism, cell differentiation, and nervous system development. Alteration of thyroid hormone levels 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 programming 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.
Introduction
The thyroid gland is one of the earliest endocrine organs that can be observed at twenty paired somites stage in a developing human embryo [1]. Thyroid hormones (THs) are first detected in the human fetal circulation at 11–13 gestation weeks [2]. The thyroid is the only endocrine gland that can produce and store thyroid hormones (THs), triiodothyronine (T3), and thyroxine (T4). T4 is the major TH secreted by the thyroid gland, whereas T3 is the main biologically active form. TH plays a crucial role in regulating different aspects of animal physiology. The major role played by TH is the regulation of metabolism, cellular growth, and development [3, 4]. However, recent advances in medical and molecular fields have helped to further dissect its other important role and mechanisms of action. TH has been shown to regulate nervous system differentiation as it influences neurogenesis, neuronal migration, neuronal and glial differentiation, myelination, and synaptogenesis [5–8]. Insufficiency in TH can lead to problems in cognition, visual attention, visual processing, motor skills, language, and memory skills [9]. TH is also implicated in neuropsychiatric disorders such as schizophrenia, bipolar disorder, anxiety, and depression [10, 11]. However, the molecular mechanisms of TH-mediated regulation of neuronal cells in these disorders are largely unknown. Some of the neurological diseases including Alzheimer’s disease (AD), Parkinson’s disease, and depression show a clear sex-specific incidence [12]. Moreover, thyroid-stimulating hormone (TSH) level has been associated with increased risk of dementia [13], and TSH level in plasma has become a routine screening test for the diagnosis of patients with suspected dementia [14]. Low and high TSH has been associated with an increased risk of developing AD in women [15]. This suggests that elucidation of TH regulation and mechanisms of action in both male and female brains could further help to understand neuronal differentiation as well as a neurological disease pathogenesis.
*TH production, transport, and mechanisms of action
*TH receptors (THRs) and distribution in the brain
*TH regulation and action in the brain
*Sex-specific effects of TH in the brain
*Thyroid hormone in neurodegenerative and psychiatric diseases
Conclusion and future perspectives
TH regulates critical biological processes including brain differentiation. TH has been shown to regulate brain differentiation, and any alteration in level could lead to various nervous system-related problems. The common neurological problems associated with TH are cognition, visual attention, visual processing, motor skills, language, and memory skills. TH shows sex-specific effects in brain cell differentiation which could lead to the differential organization of neural circuits. TH-related problems are also on the rise with females showing higher incidence. Our study suggests that there are clear sex-specific effects and regulation of TH in male and female brains. The sex-specific role of TH has started to emerge; however, critical links are missing to fully understand the molecular mechanisms. Understanding TH sex-specific effects could further help to advance the diagnostic as well as the therapeutic field.
