Hormonal amines

Feature Steroid hormones Protein/peptide hormones Amine hormones Thyroid hormones Catecholamines ... 

Hormonal amines are derived from amino acids and, in most cases, represent simple modifications of the parent compound. Table 30-1 lists the important hormonal amines, parent amino acids, major sites of synthesis, and principal actions. All of these amines except the thyroid hormones (Chapter 33) are decarboxylated products that are synthesized both in and out of the nervous system. Within the nervous system, they are important neurotransmitters outside the nervous system, the cells that produce... 

APUD (amine precursor uptake and decarboxylation) cells are derived from the neuroblast (stem cells that give rise to nerve cells and neural crest cells) or the entoderm. They have the ability to synthesize and release peptide hormones and, as their name implies, take up amine precursors (e.g., dopa) and decarboxylate them, producing hormonal amines (e.g., dopamine). 

Many hormones, such as the hormonal amines and all pep-tidic hormones, are unable to penetrate the lipid matrix of the cell membrane, and thus depend on the presence of receptor sites at the surface of target cells. As listed in Table 30-4, there are several types of cell membrane receptors for these hormones, each of which is coupled to a distinct set of intracellular postreceptor pathways. The surface receptors all initiate postreceptor events that involve the phosphorylation of one or more intracellular proteins, some of which are enzymes whose activities depend on the state of phosphorylation. In two of these cases, an intracellular second messenger is utilized to implement the hormonal action and involves G-protein-coupled receptors. One is coupled to the adenylate cyclase-cAMP system and the other is associated with the phosphatidylinositol-Ca + pathway (IP3 pathway). 

Animal hormones essentially fall into four different chemical classes (1) amine-derived hormones, (2) peptide/protein hormones, (3) steroid hormones, and (4) lipid or phospholipid hormones. Amine-derived hormones such as catecholamines and thyroxine are derivatives of the amino acids tyrosine and tryptophan. Peptide hormones including insulin, growth hormone, and vasopressin consist of polypeptides ranging in length from 5 to 200 residues. Steroid hormones such as estrogen... 

With very few exceptions, the biological activities of synthetic steroids tend to parallel those of the naturally occurring hormones on which they are patterned. Compounds with distant pharmacological activity are, as a rule, quite rare. It is thus intriguing that inclusion of a tertiary amine at the 11 position of a pregnane leads to a compound with activity far removed from its close analogues. The agent in question, minaxalone (47), exhibits anesthetic activity. 

Such difficulties prompted research workers to look for some other index of NT function in humans. These range from studies on platelets, such as abnormalities in their amine uptake and MAO activity in depressed patients, to changes in the secretion of a hormone known to be controlled by a particular NT. Thus if NA controls growth hormone release, and the secretion of the hormone is changed in depressed patients, does that confirm a role for NA in the mediation of depression ... 

Describe biochemical and functional distinctions among steroid hormones, protein/peptide hormones, and amine hormones... 

Table 10.1 Distinguishing Features of Steroid, Protein/Peptide, and Amine Hormones... 

Amine hormones include the thyroid hormones and the catecholamines. The thyroid hormones tend to be biologically similar to the steroid hormones. They are mainly insoluble in the blood and are transported predominantly (>99%) bound to proteins. As such, these hormones have longer half-lives (triiodothyronine, t3, = 24 h thyroxine, T4, = 7 days). Furthermore, thyroid hormones cross cell membranes to bind with intracellular receptors and may be administered orally (e.g., synthryoid). In contrast to steroid hormones, however, thyroid hormones have the unique property of being stored extra-cellularly in the thyroid gland as part of the thyroglobulin molecule. 

In cells that synthesize epinephrine, the final step in the pathway is catalyzed by the enzyme phenylethanolamine /V-methyltransferase. This enzyme is found in a small group of neurons in the brainstem that use epinephrine as their neurotransmitter and in the adrenal medullary cells, for which epinephrine is the primary hormone secreted. Phenylethanolamine N-methyltransferase (PNMT) transfers a methyl group from S-adenosylmethionine to the nitrogen of norepinephrine, forming a secondary amine [5]. The coding sequence of bovine PNMT is contained in a... 

Numerous reports of altered neurotransmitter and hormone functions which have been associated with the affective disorders are reviewed by Levell [142]. It was originally proposed that one or more of the neurotransmitter amines in the brain (norepinephrine, dopamine, serotonin) may be functionally elevated in manic patients and reduced in depressed patients [143]. For instance, an increase in the production of dopamine, observed in a number of case reports, is thought to be the cause of the switch into the manic phase in bipolar patients. For example, Bunney et al. reported an increase in the level of homovanillic acid (HVA), a... 

Urea ((NH2)2CO), a small and highly water soluble molecule, is an end product of amine and ammonia nitrogen metabolism and as such represents an example of biodetoxification (Section 6.4). The process is discussed in this section because it illustrates a genuine de novo biosynthetic pathway rather than detoxification involving chemical modification, via phase I and phase II reactions, of a pre-existing molecule as is the case for haem or steroid hormones. 

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