Hormone circulating forms

Certain human populations depend on dietary sources of vitamin D because of insufficient biosynthesis of the vitamin due to inadequate skin exposure to sunlight. The classic symptoms of vitamin D deficiency are rickets in children and osteomalacia in adults. 25-Hydroxyvitamin D3 is the major circulating metabolite in the blood, but the hormonally active form of the vitamin is 1,25-dihydroxyvitamin D3. The latter metabolite stimulates the intestine to absorb calcium and phosphate by two independent mechanisms and acts with parathyroid hormone to mobilize calcium, accompanied by phosphate, from the bone fluid compartment into the bloodstream. 1,25-dihydroxyvitamin D 3 is also involved in the formation of osteoclasts—giant cells that are solely responsible for the resorption of bone matrix (33). Resorption is an essential process for the development, growth, maintenance, and repair of bone. 

After secretion, the hormones circulate in blood for periods ranging from minutes (insulin) to a few hours (glycoprotein hormones). The protein hormones, being water-soluble, circulate in free form and are not bound to specific proteins. Their concentrations in blood are very low, the resting concentrations being 1CT11 M to 10 10 M. Under stimulated conditions the concentrations of peptide hormones in blood may rise 5- to 100-fold. 

Vitamin D that is taken up by the fiver is converted to 25-hydroxyvitamin D by a microsomal hydroxylase (Fig. 30-3). 25-Hydroxyvitamin D is the main circulating form of vitamin D in the serum and the best indicator of vitamin D status. Normal serum levels are 14-60 ng/mL (35-150 nmol/L). When serum calcium concentrations decline, 25-hydroxyvitamin D is converted to 1,25-dihydroxyvitmin D by la-hydroxylase, a mixed-function oxidase that is located in the inner mitochondrial membrane in kidney tissue and whose expression is regulated by parathyroid hormone (PTH). The main function of 1,25-dihydroxyvitamin D is to increase the intestinal absorption of dietary calcium and phosphorus. When serum concentrations of calcium and phosphorus are normal or when large doses of vitamin D are administered, 25-hydroxyvitamin D is metabolized to 24,25-dihydroxyvitamin D in the renal... 

The serum levels of both DHEA and androstendione decline markedly with age in both men and women (R9). DHEA and its sulfate (DHEAS), the major circulating form of DHEA, are considered to be hormone markers for aging, including cross-sectional and longitudinal linear decreases, as well as having significant stability of individual differences over time. In addition, the administration of DHEAS has been shown to enhance immune function in aging mice (D2, D4). In elderly women, serum DHEAS levels are directly correlated with bone density... 

Both dietary and endogenously synthesized vitamin D undergo 25-hy-droxylation in the liver to yield calcidiol (25-hydroxycholecalciferol), which is the main circulating form of the vitamin. This undergoes 1 -hydroxylation in the kidney to produce the active hormone calcitriol (1,25-dihydroxy-cholecalciferol) or 24-hydroxylation in the kidney and other tissues to yield 24-hydroxycalcidiol (24,25-dihydroxycholecalciferol). 

Figure 49-12 Secretion, metabolism, clearance, and circulating forms of PTH. Both intact PTH and inactive fragments containing the middle and carboxyl (C)-terminal amino acids are secreted by the parathyroid glands.These inactive fragments are also produced by peripheral metabolism of intact PTH by the liver and kidneys. Carboxyl fragments are cleared by the kidneys by glomerular filtration.The half-life and concentration of intact hormone are small compared with those of inactive fragments. (From Endres DB, Villanueva R, Sharp CF jr. Singer FR. Measurement of parathyroid hormone. Endocrinol Metab Clin North Am 1989 18 611-29.)...

The major circulating forms of thyroid hormone are thyroxine (T ), containing four iodine atoms per molecule, and triiodothyronine (Tj), with three iodine atoms per molecule. 

The introduction of rDNA human growth hormone (hGH) (70), previously isolated from cadaver pituitaries, greatly improved the long-term treatment of children who have growth failure caused by a lack of adequate endogenous hGH. The major, circulating form of human pituitary hGH is a globular protein of 191 amino acids in... 

Since hormones are substances elaborated by the cells of one tissue (endocrine tissue) to act on and control the function of cells of another tissue (target tissue) which are distant from the endocrine tissue, it seems necessary to distinguish them from those substances now classified as paracrines, chalones, and neurotransmitters. These latter compounds are hormone-like substances which are also elaborated by one tissue and which also act on different adjacent tissues. The principal difference between hormones and paracrines, chalones, and neurotransmitters is that the former have a circulating form while the latter do not. However, in many cases, neurotransmitter substances are found in nonnervous tissues where they appear to act as hormones, and thus the distinction between hormones and the other classes of signal molecules is not always sharp. 

Chalones are extracellular signal molecules that are produced and secreted by differentiated tissue and that act on adjacent cells (target cells) of adjacent tissue (target tissue) which are mitotically active. The chalones act to inhibit mitosis (see Chapter 7). Chalones are a special category of paracrine hormones and are thus not found in a circulating form. There is controversy concerning the nature and existence of chalones. 

In some cases the resulting polypeptide contains more than one hormone. The polypeptide must be cleaved at specific points to form the circulating form of each hormone. For example, in the pituitary gland, there is formed a polypeptide, now called "pro-opiocortin," containing adrenocorticotropin (ACTH) and lipotropin (LTP). This polypeptide must be hydrolyzed to produce each hormone in the free state (Mains and Eipper, 1978). 

A major role of vitamin D is to maintain the concentrations of calcium and phosphorus in the blood, primarily by enhancing the absorption of dietary calcium from the alimentary tract and regulating the interchange of calcium between blood and bone. It is likely that there are other cellular roles as yet little understood. The active form of vitamin D responsible for the hormone-like functions described above is 1,25-dihydroxycholecalciferol. Cholecalciferol, whether absorbed from the diet or synthesized in the skin, is first hydroxylated in the liver to 25-hydroxycholecalciferol. This is the main form of the hormone circulating in the blood, bound to a sterol binding protein. A further hydroxylation occurs in the kidneys to give 1,25-... 

Bone metabolism comprises the processes of bone formation and bone resorption, the key actions by which skeletal mass, structure and quality are accrued and maintained throughout life. In the mature skeleton, anabolic and catabolic actions are mostly balanced due to the tight regulation of the activity of bone forming ( osteoblast) and bone resorbing ( osteoclast) cells through circulating osteotropic hormones and locally active cytokines. 

Thyroxine (3, 5, 3,5-L-teraiodothyronine, T4) is a thyroid hormone, which is transformed in peripheral tissues by the enzyme 5 -monodeiodinase to triiodothyronine. T4 is 3-8 times less active than triiodothyronine. T4 circulates in plasma bound to plasma proteins (T4-binding globulin, T4-binding prealbumin and albumin). It is effective in its free non-protein-bound form, which accounts for less than 1%. Its half-life is about 190 h. 

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