Brain development thyroid hormones

This report has briefly summarized what we now know about thyroid hormone transport to the central nervous system. The data are still sketchy and much remains to be done. Obviously the brain is a complex organ and major differences in thyroid hormone transport and metabolism are to be expected in its constituent parts, so study of different brain regions as well as different cell types is required. We also need to distinguish between findings in the mature brain and those during fetal and postnatal development. Thyroid hormones play a very different role in these stages of the organism, and possible variations in hormone delivery to cells may contribute to these differences. Finally, in the malnutrition that often accompanies iodine deficiency, we need to ask whether PA synthesis in the choroid plexus is compromised, as it is in the liver. If so, important effects in thyroid hormone delivery to the brain may be expected. 

Dussault JH, Ruel J 1987 Thyroid hormones and brain development. Annu Rev Physiol 49 321-334... 

Hormonal actions occur during sensitive periods in development, in adult life during natural endocrine cycles and in response to experience as well as during the aging process (see Ch. 30). As a result of their fundamental actions on cellular processes and genomic activity and of the control of their secretion by environmental signals, steroid and thyroid hormone actions on the brain provide unique insights into the plasticity of the brain and behavior (see also Ch. 50). 

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

Hypothyroid women frequently have anovulatory cycles and are therefore relatively infertile until restoration of the euthyroid state. This has led to the widespread use of thyroid hormone for infertility, although there is no evidence for its usefulness in infertile euthyroid patients. In a pregnant hypothyroid patient receiving thyroxine, it is extremely important that the daily dose of thyroxine be adequate because early development of the fetal brain depends on maternal thyroxine. In many hypothyroid patients, an increase in the thyroxine dose (about 30-50%) is required to normalize the serum TSH level during pregnancy. Because of the elevated maternal TBG levels and, therefore, elevated total T4 levels, adequate maternal thyroxine dosages warrant maintenance of TSH between 0.5 and 3.0 mll/L and the total T4 at or above the upper range of normal. 

Numerous animal studies and human clinical observations show that these hormones play an essential role in pre- and post-natal brain development in vertebrates. Thus, exposure to thyroid-acting agents during fetal life and early childhood, when normal levels of thyroid hormones are crucial to growth and neurological development, should be of greatest concern. 

Zoeller RT, Crofton RM. 2000. Thyroid hormone action in fetal brain development and potential for distribution by environmental chemicals. Neurotoxicology 21(6) 935-946. 

There is no such clear cut difTcrcnlialiun as metamorphosis in the mammal, but development is an extremely complex process and has been shown to depend upon the presence of adequate amounts of thyroid hormones. Deficient development, especially of the central nervous system, is marked in ehildren suffering from thyroid deficiency early in life, ansi this inadequacy cannot be overcome completely by medication commenced after the first few weeks. In the adult, thyroxine is important in the maintenance of energy turnover in most of the tissues of the body, such as the heart, skeletal muscle, liver, and kidney, Other physiological functions, most notably brain aclivity and reproduction, are also dependent upon thyroxine, although the metabolic rales of the tissues concerned in these functions do not seem to be altered. 

Thyroid hormones Thyroxine Thyroid gland Fetal brain and bone development, oxygen consumption, gut motility... 

Porterfield SP Hendry LB (1998) Impact of PCBs on thyroid hormone directed brain development. Toxicol Ind Health, 14 103-120. 

Sher ES, Xu XM, Adams PM, Craft CM, Stein SA (1998) The effects of thyroid hormone level and action in developing brain Are these targets for the actions of polychlorinated biphenyls and dioxins Toxicol Ind Health, 14 121-158. 

It has long been known that thyroid hormone deficiency, when established prior to the critical period of brain development, produces severe and permanent mental retardation both in humans ( cretinism ) and in experimental animals (see Refs. 6 and 101). Most of the early studies aimed at describing the behavioural, physiolog-... 

Bernal J, Nunez J (1995) Thyroid hormones and brain development. Eur J Endocrinol 755 390-398. 

Oppenheimer JH, Schwartz HL (1997) Molecular basis of thyroid hormone-dependent brain development. Endocrine Rev 75 462-475. 

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