Thyroid Hormones Are the Primary Factors for the Control of Basal Metabolism
The mechanism of action of thyroid hormones at the cellular level is based on their ability to penetrate the cell membrane even though they are amino acids; in essence, they are lipophilic.
Although it is thought that thyroid hormones interact directly with the nucleus to initiate the transcription of messenger ribonucleic acid (mRNA) (Figure 34-5), the presence of T3 receptors has been reported on mitochondria.Thyroid hormones are likely the primary determinants of basal metabolism. It is difficult to define their precise physiological effects, however, because many of the effects of thyroid hormones have been demonstrated through the creation of hypothyroid or hyperthyroid states. Nevertheless, it has long been recognized that thyroid hormones increase oxygen consumption of tissues and, as a result, heat production. This effect is known as the calorigenic effect. One site of action of the calori- genic effect of thyroid hormones is within the mitochondrion.
Thyroid hormones affect carbohydrate metabolism in several ways, including increasing intestinal glucose absorption and
FIGURE 34-5 Proposed Subcellular mechanism of thyroid hormone action. mRNAf Messenger ribonucleic acid; Rf receptor. (From Hedge GA, Colby HD, Goodman RL: Clinical endocrine physiology, Philadelphia, 1987, Saunders.)
facilitating the movement of glucose into both fat and muscle. Furthermorejhyroid hormones facilitate insulin-mediated glucose uptake by cells. Glycogen formation is facilitated by small amounts of thyroid hormones; however, glycogenolysis occurs after larger dosages.
Thyroid hormones in concert with growth hormone are essential for normal growth and development. This is accomplished in part by the enhancement of amino acid uptake by tissues and enzyme systems that are involved in protein synthesis.
Whereas thyroid hormones affect all aspects of lipid metabolism, the emphasis is placed on lipolysis. One particular effect of thyroid hormones is the tendency to reduce plasma cholesterol levels. This appears to involve both increased cell uptake of low-density lipoproteins (LDLs) with associated cholesterol molecules and a tendency for increased degradation of both cholesterol and LDL. These effects on lipid metabolism are usually seen in pathophysiological situations involving hypersecretion of thyroid hormone or in thyroid deficiency states in which hypercholesterolemia is a hallmark of thyroid deficiency. In this same context, the effects of thyroid hormones on metabolic processes, including carbohydrate, protein, and lipid metabolism, are often described as catabolic.
Thyroid hormones have noteworthy effects on the nervous and cardiovascular systems. The effects of the sympathetic nervous system are enhanced by the presence of thyroid hormones. This is thought to occur through thyroid stimulation of β-adrenergic receptors in tissues that are targets for the catecholamines, such as epinephrine and norepinephrine. In the central nervous system (CNS), thyroid hormones are important for normal development of tissues in the fetus and neonate; inhibition of mental activity occurs when thyroid hormone exposure is inadequate. In humans, persons with hypothyroid activity are mentally dull and lethargic, which suggests that normal CNS function in the adult depends on the presence of adequate amounts of thyroid hormone.
Thyroid hormones increase the heart rate and force of contraction, probably through their interaction with the catecholamines. This interaction is caused by an increase in tissue responsiveness through the induction of Catecholaminergic β receptors by thyroid hormones. Blood pressure is elevated because of increased systolic pressure, with no change in diastolic pressure; the end result is an increase in cardiac output.
These responses are most easily observed in situations of increased thyroid activity. In regard to the effect of thyroid hormones on cardiovascular activity, it may be concluded that they are important for maintaining normal contractile activity of cardiac muscle, including the transmission of nerve impulses.Thyroid hormone was used in classic experiments involving the metamorphosis of amphibian larvae. Thyroxine administration causes the differentiation of tadpoles into frogs, whereas thyroidectomy results in development into large tadpoles. Thyroid-induced metamorphosis is limited to amphibians, but
FIGURE 34-6 Hypothalamopituitary-thyroid axis. Plus signs indicate stimulation; minus signs indicate inhibition. T3, Triiodothyronine; T4, thyronine; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone. (From Hedge GA, Colby HD, Goodman RL: Clinical endocrine physiology, Philadelphia, 1987, Saunders.)
thyroid hormones are important for many (subtle) aspects of differentiation in other classes of animals.
Thyroid hormone activity is usually defined in terms of tissue or organ responses to inadequate or excessive amounts of hormone. A more balanced view is that thyroid hormones are important for the normal metabolic activity of all tissues.
TSH, or thyrotropin, is the most important regulator of thyroid activity. It acts through the initiation of cyclic adenosine 3',5'-monophosphate (cAMP) formation and the phosphorylation of protein kinases. I hyrotropin secretion is regulated by thyroid hormones through negative-feedback inhibition of the synthesis of thyrotropin-releasing hormone (TRH) at the level of the hypothalamus and by inhibition of TSH activity at the level of the pituitary gland (Figure 34-6).