Thyrotropin from pituitary

Located in close proximity to the primary capillary plexus in the hypothalamus are specialized neurosecretory cells. In fact, the axons of these cells terminate on the capillaries. The neurosecretory cells synthesize two types of hormones releasing hormones and inhibiting hormones (see Table 10.2). Each of these hormones helps to regulate the release of a particular hormone from the adenohypophysis. For example, thyrotropin-releasing hormone produced by the neurosecretory cells of the hypothalamus stimulates secretion of thyrotropin from the thyrotrope cells of the adenohypophysis. The hypo-thalamic-releasing hormone is picked up by the primary capillary plexus travels through the hypothalamic-hypophyseal portal veins to the anterior pituitary leaves the blood by way of the secondary capillary plexus and exerts its effect on the appropriate cells of the adenohypophysis. The hypophyseal hormone, in this case, thyrotropin, is then picked up by the secondary capillary plexus, removed from the pituitary by the venous blood, and delivered to its target tissue. 

Many small peptides exert their effects at very low concentrations. For example, a number of vertebrate hormones (Chapter 23) are small peptides. These include oxytocin (nine amino acid residues), which is secreted by the posterior pituitary and stimulates uterine contractions bradykinin (nine residues), which inhibits inflammation of tissues and thyrotropin-releasing factor (three residues), which is formed in the hypothalamus and stimulates the release of another hormone, thyrotropin, from the anterior pituitary gland. Some extremely toxic mushroom poisons, such as amanitin, are also small peptides, as are many antibiotics. 

Thyrotropin-releasing factor (TRF) is produced in the hypothalamus and arrives at the pituitary via the hypophyseal portal blood system. TRF mediates the release of thyrotropin from the anterior hypophysis. The thyrotropin release is inhibited by thyroxine, presumably free thyroxine, and the inhibition is dose dependent. Thus excessive levels of thyroxine depress thyrotropin release, and lower thyroxine levels result in increased thyrotropin release from the anterior pituitary. TSH, in turn, stimulates thyroid hormone synthesis and secretion by the thyroid gland. Thyroxine and triiodothyronine are bound to specific binding proteins in the blood. The amounts and binding constants of the specific thyroid-binding proteins, together with the rate of thyroid hormone release from the thyroid, determine the amount of free thyroxine in the blood. Free thyroxine levels are determined not only by the rate of... 

B12. Bowers, C. Y., Lee, K. L., and Schally, A. V., Effect of Actinomycin D on hormones that control the release of thyrotropin from the anterior pituitary glands of mice. Endocrinology 82, 303-310 (1968). 

B15. Bowers, C. Y., Schally, A. V., Reynolds, G. A., and Hawley, W. D., Interactions of 1,-thyroxine or L-triiodothyronine and thyrotropin-releasing factor on the release and synthesis of thyrotropin from anterior pituitary gland of mice. Endocrinology 81, 741-747 (1967). 

C. Thyrotropin-Releasing Hormone (TRH) TRH is a tripeptide that stimulates release of thyrotropin from the anterior pituitary. TRH also increases prolactin production bul has no effect on the release of growth hormone or ACTH. 

The following molecule is thyrotropin-releasing hormone (TRH). It is secreted by the hypothalamus, causing the release of thyrotropin from the pituitary gland, which, in turn, stimulates the thyroid gland. The thyroid produces hormones, such as thyroxine,... 

Secondary hypothyroidism, or pituitary hypothyroidism, is the consequence of impaired thyroid-stimulating hormone (TSH) secretion and is less common than primary hypothyroidism. It may result from any of the causes of hypopituitarism (e.g., pituitary tumor, postpartum pituitary necrosis, trauma). Patients with secondary hypothyroidism exhibit undetectable or inappropriately low serum TSH concentrations. In secondary hypothyroidism, a normal thyroid gland lacks the normal level of TSH stimulation necessary to synthesize and secrete thyroid hormones. Such patients usually also have impaired secretion of TSH in response to exogenous thyrotropin-releasing hormone (TRH) administration. 

Thyrotropin-releasing hormone is one of several small peptide hormones secreted by the anterior lobe of the pituitary gland. These are the master" hormones that function to stimulate hormone secretion from other endocrine glands. Thyrotropin stimulates the functioning of the thyroid gland. 

The secretion of thyroid hormones starts with endocy-tosis of the modified thyroglobulin, followed by fusion of the endocytotic vesicles with lysosomes. The lysosomal enzymes then degrade the thyroglobulin, liberating triiodothyronine and thyroxine into the circulation. Only about five molecules of T3 and T4 are generated from each molecule of thyroglobulin. Thyroid hormone secretion is stimulated by thyrotropin (TSH), a pituitary hormone that activates adenylate cyclase in its target cells. 

Thyroid hormone production is controlled by the hypothalamic-pituitary system (see Chapter 28). Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the release of thyroid-stimulating hormone (TSH) from the anterior pituitary.17,63 TSH then travels via the systemic circulation to the thyroid gland to stimulate the production of thyroxine and triiodothyronine. 

Anterior pituitary hormones include growth hormone (GH), thyrotropin (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and adrenocorticotropin (ACTH). Another peptide, B-lipotropin (B-LPH), is derived from the same prohormone, proopiomelanocortin, as ACTH. B-LPH is secreted from the pituitary (along with ACTH), and is a precursor of the opioid peptide B-endorphin (see Chapter 31 Opioid Analgesics Antagonists). 

Ishibashi M, Yamaji T (1984) Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture, J Clin Invest 75 66-78. 

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