Give a detailed account of the hormonal regulation of growth.

Outline:

·        Definition

·        Effects of growth hormone, somatomedins, thyroid hormone and sex hormones on:

- linear growth (cartilage formation, bone formation, bone resorption)

- epiphyseal growth plate

- ECF volume

- functional capacity of organs

Essay:

            Growth is reflected by an increase in cell number, cell size and intracellular substance. It is normally accompanied by an orderly sequence of maturational changes, and it involves accretion of protein and increase in size and length, and weight, which may be due to the formation of fat or retention of salt and water.

            In humans, there are 2 periods of rapid growth, the first in infancy and the second in late puberty just before growth stops. The first period of accelerated growth is partly a continuation of the fetal growth period. The second growth spurt at the time of puberty is due to growth hormone, androgens, and estrogens, and the subsequent cessation of growth is due in large part to the androgens and estrogens.

            Growth is a complex phenomenon that is affected not only by growth hormone and somatomedins, but also by thyroid hormones, androgens, estrogens, glucocorticoids and insulin. It is also affected by genetic factors and it depends on an adequate nutrition. Growth hormone is the primary hormone responsible for postnatal somatic growth and development and helps to maintain normal lean body mass and bone mass in adults. The effects of thyroid hormone on growth and development is most marked after during infancy; its influence gradually decline and stops after puberty. Androgens and estrogens are responsible for the growth spurt during puberty and they are responsible for terminating growth eventually.

            Growth hormone (GH) is a single-chain polypeptide originating from the anterior pituitary somatotrophs. The synthesis of GH is increased by its specific hypothalamic growth hormone-releasing hormone (GHRH) and is decreased by somatostatin, its hypothalamic inhibitor. Plasma growth hormone is elevated in newborns. Subsequently, average resting levels fall, but the spikes of growth hormone secretion are larger during puberty so that mean plasma level is increased.

            GH is a hormone with profound anabolic action. In its absence, growth is stunted in humans. More importantly, GH stimulates a number of adaptations that are essential for maintaining an increased body mass such as increasing cardiac output (to pump more blood) and reabsorption of calcium (for bone growth). The most striking and specific effect of GH is the stimulation of linear growth that results from GH action on the epiphyseal cartilage or growth plates of long bones. All aspects of the metabolism of the cartilage-forming cells, the chondrocytes, are stimulated. These metabolic effects include the incorporation of sulfate into proteoglycan chondroitin. Together, chondroitin and collagen form the resilient extracellular matrix of cartilage. GH also stimulates the proliferation of chondrocytes, as well as their synthesis of DNA, RNA, and proteins and increasing the activity and number of bone-remodeling units. GH also supports protein synthesis by stimulating cellular uptake of amino acids.

            Visceral organs (liver, kidney, pancreas, intestines), endocrine glands (adrenals, parathyroids, pancreatic islets), skeletal muscle, heart, skin, and connective tissue all undergo hypertrophy and hyperplasia in response to GH. In most instances, the functional capacity of the enlarged organ is enhanced. GH increases cardiac muscle size and contractility and it induces muscle enzymes involved in contraction. The net result is an increase in cardiac output. GH increases the volume of the extracellular fluid by stimulating the renin-angiotensin-aldosterone axis and by suppressing atrial naturietic peptide. Proximal tubular phosphate reabsorption is increased. Calcium absorption from the intestine is enhanced, probably by GH stimulation of vitamin D production.

            The effects of growth hormone on growth, cartilage, and protein metabolism depend on an interaction between growth hormone and somatomedins which are related to a number of growth factors that affect many different tissues and organs. These include nerve growth factor, epidermal growth factor and platelet-derived growth factor. The principal circulating somatomedins are insulinlike growth factor 1, IGF-1 and IGF-2. IGF-1 synthesis is GH dependent, and its levels correlate well with the progression of pubertal growth. IGF-II stimulates placental growth and growth of both the preimplantation and postimplanation embryo. GH and IGF-1 are also important for normal development and function of the immune system. Both molecules are produced by monocytes-macrophages.

            Thyroid hormones (T₃) are necessary for a completely normal rate of GH secretion. They have widespread effects on the ossification of cartilage, the growth of teeth, the contours of the face, and the propoprtions of the body. In humans, thyroid hormone stimulates endochondral ossification, linear growth of bone, and maturation of epiphyseal bone centers. T₃ enhances the maturation and activity of chondrocytes in the cartilage growth plate, in part by increasing local somatomedin production and action. Thyroid hormone is not essential for linear growth until after birth, but it is already essential for normal maturation of growth centers in the bones of the developing fetus. T₃ also stimulates adult bone remodeling, and T₃ receptors are present in osteoblasts. Increased osteoid and bone formation are manifested by increases in plasma levels of alkaline phosphatase and osteocalcin. The regular progression of tooth development and eruption depends on thyroid hormone, as does the normal cycle of growth and maturation of the epidermis, its hair follicles and nails. Thyroid hormone alters the characteristics of subcutaneous tissue by inhibiting the synthesis and increasing the degradation of mucopolysaccharides in the intercellular ground substance.

            Although androgens and estrogens initially stimulate growth, they ultimately terminate growth by causing the epiphyses to fuse in the long bones, causing the epiphyses to fuse to the long bones. Once the epiphyses have closed, linear growth ceases. Testosterone stimulates the pubertal growth spurt. Androgen receptors in osteoblasts transduce testosterone-stimulated increases in levels of growth factors. Testosterone increases body muscle mass and enhances accumulation of upper body, abdominal and visceral fat. Estradiol accelerates linear growth too. Estrogen inhibits bone resorption directly by its effects on osteoclasts, and indirectly by suppressing resorptive cytokines. Bone formation may be increased by estrogens via induction of focal growth factors. Reabsorption of sodium from the renal tubules is stimulated by estradiol. As the epiphyseal growth centers are more sensitive to estrogens than to testosterone, they close sooner which explains the shorter average height of women.

            In short, growth is mediated mainly by the hormones growth hormone, somatomedins, thyroid hormone, androgens and estrogens. The latter two are responsible for terminating growth towards the end of puberty.