Chemical Structure and Synthesis of Hormones
There are three general classes of hormones:
1. Proteins and polypeptides, including hormonessecreted by the anterior and posterior pituitary gland, the pancreas (insulin and glucagon), the parathyroid gland (parathyroid hormone), and many others (see Table 74–1).
2. Steroids secreted by the adrenal cortex (cortisoland aldosterone), the ovaries (estrogen and progesterone), the testes (testosterone), and the placenta (estrogen and progesterone).
3. Derivatives of the amino acid tyrosine, secretedby the thyroid (thyroxine and triiodothyronine) and the adrenal medullae (epinephrine and norepinephrine). There are no known polysaccharides or nucleic acid hormones.
Polypeptide and Protein Hormones Are Stored in Secretory Vesi-cles Until Needed. Most of the hormones in the bodyare polypeptides and proteins. These hormones range in size from small peptides with as few as 3 amino acids (thyrotropin-releasing hormone) to proteins with almost 200 amino acids (growth hormone and prolactin). In general, polypeptides with 100 or more amino acids are called proteins, and those with fewer than 100 amino acids are referred to as peptides.
Protein and peptide hormones are synthesized on the rough end of the endoplasmic reticulum of the dif-ferent endocrine cells, in the same fashion as most other proteins (Figure 74–2). They are usually synthe-sized first as larger proteins that are not biologically active (preprohormones) and are cleaved to form smaller prohormones in the endoplasmic reticulum. These are then transferred to the Golgi apparatus for packaging into secretory vesicles. In this process, enzymes in the vesicles cleave the prohormones to produce smaller, biologically active hormones and inactive fragments. The vesicles are stored within the cytoplasm, and many are bound to the cell membrane until their secretion is needed. Secretion of the hor-mones (as well as the inactive fragments) occurs when the secretory vesicles fuse with the cell membrane and the granular contents are extruded into the interstitial fluid or directly into the blood stream by exocytosis.
In many cases, the stimulus for exocytosis is an increase in cytosolic calcium concentration caused by depolarization of the plasma membrane. In other instances, stimulation of an endocrine cell surface receptor causes increased cyclic adenosine monophos-phate (cAMP) and subsequently activation of protein kinases that initiate secretion of the hormone. The peptide hormones are water soluble, allowing them to enter the circulatory system easily, where they are carried to their target tissues.
Steroid Hormones Are Usually Synthesized from Cholesterol and Are Not Stored. The chemical structure of steroid hor-mones is similar to that of cholesterol, and in most instances they are synthesized from cholesterol itself.
They are lipid soluble and consist of three cyclohexyl rings and one cyclopentyl ring combined into a single structure (Figure 74–3).
Although there is usually very little hormone storage in steroid-producing endocrine cells, large stores of cholesterol esters in cytoplasm vacuoles can be rapidly mobilized for steroid synthesis after a stim-ulus. Much of the cholesterol in steroid-producing cells comes from the plasma, but there is also de novo synthesis of cholesterol in steroid-producing cells. Because the steroids are highly lipid soluble, once they are synthesized, they simply diffuse across the cell membrane and enter the interstitial fluid and then the blood.
Amine Hormones Are Derived from Tyrosine. The two groupsof hormones derived from tyrosine, the thyroid and the adrenal medullary hormones, are formed by the actions of enzymes in the cytoplasmic compartments of the glandular cells. The thyroid hormones are synthesized and stored in the thyroid gland and incor-porated into macromolecules of the protein thy-roglobulin, which is stored in large follicles withinthe thyroid gland. Hormone secretion occurs when the amines are split from thyroglobulin, and the free hormones are then released into the blood stream. After entering the blood, most of the thyroid hor-mones combine with plasma proteins, especially thy-roxine-binding globulin, which slowly releases thehormones to the target tissues.
Epinephrine and norepinephrine are formed in the adrenal medulla, which normally secretes about four times more epinephrine than norepinephrine. Cate-cholamines are taken up into preformed vesicles and stored until secreted. Similar to the protein hormones stored in secretory granules, catecholamines are also released from adrenal medullary cells by exocytosis. Once the catecholamines enter the circulation, they can exist in the plasma in free form or in conjugation with other substances.
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