The hypothalamic-pituitary thyroid releasing hormone is the most important regulator of thyroid gland function and growth. It stimulates every aspect of thyroid function, including the pinocytosis of colloid droplets in the cytoplasm and the proteolysis of thyroglobulin to release T4 and T3. TSH also increases iodide uptake and TPO activity. Intermediate effects of TSH involve protein synthesis and the expression of genes encoding NIS, thyroglobulin, and TPO. Sustained TSH stimulation leads to hypertrophy and hyperplasia of follicular cells, accompanied by increased thyroid blood flow. Lack of adequate iodine in the diet can cause a noticeable enlargement of the thyroid gland called goiter. Thyroid hormone has diverse physiological effects on various cells and tissues and plays a crucial role in optimizing the actions of other hormones and neurotransmitters. The cardiac muscle, for instance, is influenced by thyroid hormone through mechanisms such as changes in myosin heavy chain ratio, Na+/K+-ATPase activity, sarcoplasmic Ca-ATPase, and β-adrenergic signaling.
The most important regulator of thyroid gland function and growth is the hypothalamic-pituitary thyroid releasing •Fig. 42.8 TransportofT4andT3inserumbytransportproteinsandpercentagesofboundandfreehormone.Thyroid secretion Protein-Bound T4 (99.98%) & T3 (99.7%) Thyroid-binding globulin (TBG) Transthyretin (TTR) Albumin • Feedback • Activation to T3 • Inactivation • Excretion • Tissue actions • Feedback • Inactivation • Excretion Free T4 (0.02%) & T3 (0.3%) Total T4 8 µg/dL Total T3 0.14 µg/dL Free T4 1.6 ng/dl Free T3 – 0.42 ng/dl T3 T4 123I Uptake (% of dose) •Fig. 42.9 Thyroidglandiodothyronineuptakedefectiveorganificationstates.
). TSH stimulates every aspect of thyroid function. TSH has immediate, intermediate, and long-term actions on the thyroid epithelium. Rapid actions of TSH include pinocytosis of colloid droplets in the cytoplasm, which represent thyroglobulin within endocytic vesicles (see
Fig. 42.7 ). TSH stimulates the proteolysis of thyroglobulin and release of T4 and T3 from the gland. Iodide uptake and TPO activity increase. TSH also stimulates entry of glucose into the hexose monophosphate shunt pathway, which generates the reduced nicotinamide adenine dinucleotide phosphate (NADPH) needed for the peroxidase reaction. Intermediate effects of TSH on the thyroid gland occur after hours to days and involve protein synthesis and expression of numerous genes, including those encoding NIS, thyroglobulin, and TPO. Sustained TSH stimulation leads to the long-term effects of hypertrophy and hyperplasia of follicular cells. Capillaries proliferate and thyroid blood flow increases. These actions, which underlie the growth-promoting effects of TSH on the gland, are supported by local production of growth factors. A noticeably enlarged thyroid gland is called a goiter (
Fig. 42.10 ). Endemic goiter is due to lack of adequate iodine in the diet, which results in low thyroid hormone and elevated TSH levels.
Physiological Effects of Thyroid Hormone
Thyroid hormone acts on essentially all cells and tissues, and imbalances in thyroid function constitute some of the most common endocrine diseases. Thyroid hormone has many direct actions, but it also acts in more subtle ways to optimize the actions of several other hormones and neurotransmitters.
curvesfornormal,hypothyroid,hyperthyroid,and •Fig. 42.10 Thethyroidglandislocatedintheanterioraspectoftheneck,whereitiseasilyvisualizedwhenenlarged(goiter).
˜ Cardiac muscle Myosin heavy chain ˝/˙ ratio Na+, K+-ATPase Sarcoplasma Ca-ATPase ˙-Adrenergic signaling G-protein stimulatory/ •Fig. 42.11 Mechanismsbywhichthyroidhormoneincreasescardiacoutput.Theindirectmechanismsareprobablyquantitativelymoreimportant.