Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intra- and Intercellular Communication
Characteristics of the Endocrine System
Diversity of the Endocrine System

One of the most remarkable Properties of the Endocrine System is that it provides the body with multiple ways to solve emerging problems. In this section, we will briefly discuss specific Examples illustrating this diversity.

Tissue Origin and Localization of Endocrine glands

Most endocrine glands develop from epithelial Cells. Important exceptions to this rule are the testosterone-producing Leydig cells in the Testes and the estrogen-producing granulosa Cells of the Ovaries, which are of Connective Tissue origin, as well as the secretory cells of the neurohypophysis (which differentiate from neural tissue cells). It is suggested that during Embryogenesis, certain types of endocrine cells originated from the neural crest (neural plate). If so, The Link Between the nervous and endocrine systems becomes clear. Neural crest tissue can end up in any organ, which is why some Hormones are synthesized in the Brain and in Tissues derived from the foregut and midgut. Furthermore, this explains syndromes of ectopic hormone production—i.e., The production of hormones by the 'wrong' tissue, such as the production of parathyroid hormone (PTH) and ACTH by malignant cells in cases of Lung Cancer. These syndromes typically involve a rather limited number of Peptide Hormones, but A wide variety of tissues. They are believed to be caused by the activation of 'silent' genes in a given Cell, though it is also possible that the activation involves 'silent' cells present in the tissue that are embryologically related to endocrine gland cells. Another curious example is multiple endocrine neoplasia (MEN) syndromes, which are characterized by familial clustering. These syndromes feature the Excessive production of peptide hormones or catecholamines, often with multiple Hormones of the same Class being produced within a single tissue.

The distribution of hormone-producing cells is not accidental; they are present in various tissues for specific reasons. Locally elevated concentrations of certain hormones (compared to their plasma concentrations) often serve as a prerequisite for specific physiological processes. For example, Spermatogenesis requires a higher level of testosterone than is found in plasma; accordingly, the testosterone-secreting Leydig cells and seminiferous tubules are located adjacent to each other. The formation of the corpus luteum requires a very high concentration of estrogens, and accordingly, it is surrounded by granulosa cells. The primary Action of Insulin and Glucagon is The regulation of hepatic glucose production; thus, There is a close anatomical relationship between the pancreatic islets and the hepatic portal Circulation. In The adrenal medulla, high concentrations of cortisol induce phenylethanolamine-N-methyltransferase (the rate-limiting enzyme in catecholamine Biosynthesis); cortisol reaches this tissue via portal vessels originating from the adrenal cortex. A close anatomical relationship exists between the Hypothalamus and the anterior pituitary, allowing the highly labile hypothalamic releasing hormones to rapidly reach their target—the Pituitary Gland—transported by Blood through another specialized portal system. Finally, completely unique anatomical relationships have evolved among various cells of the pancreatic islets, enabling these cells to regulate each other's secretory activity through local concentration gradients of Somatostatin, Pancreatic Polypeptide, glucagon, and insulin.

Biosynthesis and Conversion of Hormones

Both the Chemical Nature of active hormones and the mechanisms of their biosynthesis and post-synthetic conversions are highly diverse. Hormones are formed from lipid precursors through the Modification of the amino acid Tyrosine, or via Protein Synthesis (simple and complex Peptides, and carbohydrate-containing Glycoproteins).

Some hormones are synthesized and secreted directly in their final active form; examples include aldosterone, hydrocortisone, triiodothyronine (T₃), estradiol, and catecholamines. Other Hormones must undergo intracellular modification prior to secretion or in order to acquire full biological activity. For instance, insulin is synthesized as proinsulin, a typical precursor protein, whereas parathyroid hormone (PTH) has at least two precursor peptides containing prepro-sequences, the Cleavage of which is necessary for full biological activity. A description of precursor Proteins, their synthesis, and their conversion into the final product (intracellular Processing) can be found in Chapter 42. Let us mention a more complex case: pro-opiomelanocortin (POMC), a peptide consisting of 285 amino acid residues and the product of a single Gene; its cleavage yields ACTH, ß-lipotropin, ß-endorphin, a-MSH, and ß-MSH, and it is possible that the POMC precursor contains sequences representing as-yet-unidentified peptide hormones. Precursor molecule processing exhibits tissue Specificity (see Chapter 45).

Perhaps the most striking example of a disproportionately large precursor is thyroglobulin. This large protein (mol. mass 660,000) is present in the lumen of thyroid follicles. It contains 5,000 amino acid residues, including 120 tyrosine residues, only a fraction of which undergo iodination during the synthesis of THYROID HORMONES (see Chapter 46). Ultimately, the entire thyroglobulin molecule undergoes proteolysis to release only a few molecules of T₃ and tetraiodothyronine (T₄).

In peripheral tissues, certain hormones are converted into more active compounds. This can occur in target tissues—for example, T₄ is converted to T₃ in The Liver and pituitary, and testosterone to dihydrotestosterone in androgen-responsive tissues. Peripheral conversion can also take place in non-target tissues. For instance, dehydroepiandrosterone is synthesized in the Adrenal Glands and converted to androstenedione in the liver; the latter is subsequently converted into testosterone, estrone, or estradiol in adipose tissue, liver, and Skin cells. A combined conversion of an inactive compound into an active hormone in both peripheral target and non-target tissues is also possible. An example is The conversion of vitamin D₃ (derived from the skin) to 25-hydroxycholecalciferol in the liver, followed by the formation of 1,25-dihydroxycholecalciferol in the Kidneys (Chapter 47). Hormones secreted by different tissues and exhibiting varying cellular specificity may share structural similarities. Thus, the glycoprotein hormones of the pituitary and Placenta (TSH, LH, FSH, and hCG) are heterodimers composed of a- and ß-subunits, and their a-subunits are identical.