Thyroid system control

DEVELOPMENT OF FETAL THYROID SYSTEM CONTROL Delbert A. Fisher... 

The central focus of thyroid system control is the pituitary thyrotroph cell. Figure 1 summarizes the major events in thyrotroph cell control of thyrotropin (TSH) synthesis and release. Hypothalamic thyrotropin releasing hormone (TRH) binds to its receptor, stimulating the synthesis and release of TSH. Based on available evidence it appears that TRH-receptor Interaction increases intracellular free calcium concentrations both by mobilization from intracellular pools and by increasing transport via cell membrane calcium channels (2). The increased cytoplasmic calcium activates TSH release. Cyclic AMP may play a role both TRH and cAMP seem capable of increasing calcium inflow into the thyrotroph, as well as mobilizing calcium from intracellular pools. However, cAMP does not appear to be the primary mediator of the TRH effect. 

After these initial steps, TIQDT was tested for its capacity to screen environmentally relevant compounds. 2,4-Dichlorophenoxyacetic acid (2,4-D), l,l-bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT), and 4-nonylphenol (4-NP) were selected as they are usually considered to be TGFDs [52-55]. Reports concerning the effect of methyhnercury (MeHg) on thyroid function are contradictory [56-58]. Two environmentally relevant compounds with no reported effects on the thyroid system, fenoxicarb and atrazine [59, 60], were included as negative controls to assess the specificity of the assay. Our data strongly suggest that TIQDT may be... 

Thyroid hormone release is subject to the negative feedback strategy that is typical of endocrine systems controlled by the hypothalamic-pituitary axis. Increased circulating levels of the thyroid hormones (T4, T3) serve to limit their own production by inhibiting TRH release from the hypothalamus and TSH release from the anterior pituitary.30,35 This negative feedback control prevents peripheral levels of thyroid hormones from becoming excessively high. 

It has also been mentioned that salt iodization efficacy, the preferred strategy for IDD, might be influenced by ID, because this disorder impairs thyroid metabolism (WHO, 2001, Zimmermann et al., 2000). It has been observed that two initial steps in thyroid hormone synthesis are catalyzed by Fe-dependent thyroid peroxidase (TPO). One Fe-defl-ciency anemia study in rats showed reduced TPO activity, and decreased plasma T4 and triiodothyronine (T3) levels (Hess et al, 2002). IDA may also alter the central nervous systems thyroid metabolism control, and reduce T4 to T3 peripheral conversion (Beard etal, 1998), modify nuclear T3 binding (Smith et al, 1994), and increase circulating thyrotropin (TSH) (Beard et at, 1990). The therapeutic response to oral iodized oil is impaired in children with IDA compared with Fe-sufficient children (Zimmermann et al, 2000). 

The thyroid hormones control metabolism. They increase cardiac output and the excitability of the nervous system. In children, the maturing of the cerebral cortex, of the skeleton, the musculature and the genitalia, is stimulated. Both hormones are active only in their protein-imbound state. Free thyroxine and 3,3 ,5-triiodothyronine bind to receptors in the ceU nucleus and in the mitochondria, where they activate protein synthesis and the production of adenosine triphosphate. 

Since the brain contains receptors and is a developmental and homeostatic target for thyroid hormones, a mechanism must exist which discriminates between neural and peripheral tissue-specific functions under thyroid hormone control. We describe here the properties of a thyroid hormone receptor predominantly expressed in the rat brain. We also present in situ hybridization histochemistry data outlining the brain subregions containing this receptor mRNA. Its characterization implies a multiple receptor system which may help to explain some of the tissue-specific physiological effects of thyroid hormones. 

Reports of the effects of Li+ upon the thyroid gland and its associated hormones are the most abundant of those concerned with the endocrine system. Li+ inhibits thyroid hormone release, leading to reduced levels of circulating hormone, in both psychiatric patients and healthy controls [178]. In consequence of this, a negative feedback mechanism increases the production of pituitary TSH. Li+ also causes an increase in hypothalamic thyroid-releasing hormone (TRH), probably by inhibiting its re-... 

Endocrine diseases and their treatment have a major impact on health throughout the world, particularly in terms of diabetes, thyroid disease, steroid therapy, and control of fertility. Most endocrine therapy is simple and relatively cheap, but a clear understanding of their actions and uses is essential for safe and cost-effective treatment. In this chapter we will focus mainly on well established and validated endocrine therapies that are widely used throughout the world, with briefer mention of drugs that have recently been introduced. In the sections that follow we outline the major issues in the current clinical pharmacology of endocrine disease, covering each of the major endocrine systems in turn. 

---