Human Growth Hormone (GH)

• Human Growth Hormone (GH), also known as somatotropic hormone or somatotropin, is crucial for growth.
• GH is a small protein composed of 191 amino acids in a single chain.
• It facilitates growth in almost all body tissues capable of growing.
• GH is the single most important hormone for normal growth into adulthood
• GH has profound effects on protein, carbohydrate, and fat metabolism.
• GH increases protein production but decreases glucose usage.
• GH increases fatty acid release from adipose tissue.
• GH and IGF-1 have negative feedback loops that feed back on the somatotrophs in the anterior pituitary to decrease GH secretion.
• GH inhibits its own secretion via a "short-loop" feedback on somatotrophs.
• IGF-1 inhibits GH release by increasing somatostatin secretion as well as suppressing GHRH release.
• IGF-1 directly inhibits GH release by suppressing the somatotrophs.
• GH stimulates the secretion of IGF-1 from peripheral target tissues.
• GH has a half-life of 6-20 minutes
• GH is carried in the plasma by a carrier protein.
• Somatostatin is involved in the regulation of GH.
• Strenuous exercise and deep sleep increase GH secretion.
• GH has minimal to no effect on fetal growth.
• Secretion rate increases steadily from birth to early childhood before remaining relatively stable.
• GH secretion has an enormous burst at puberty.
• As age increases, the average plasma concentration of GH decreases.
• "Somatomedin" refers to insulin-like growth factors (IGF).
• IGFs are mainly produced in the liver.
• IGFs activate cartilage metabolism and cell division.
• Growth hormone stimulates the synthesis of DNA, RNA, and protein in nearly all organs.
• IGF-I stimulates neuron development early in the postnatal period.
• GH and IGF-I are important in development and normal immune system functions.
• IGF-II stimulates placental and prenatal fetal growth before birth.
• GH travels from the anterior pituitary to the liver and other tissues, resulting in insulin-like growth factors.
• GH causes hypertrofy & hyperplasia in all tissues
• GH increases calcium absorption from the intestines.
• GH stimulates the renin-angiotensin-aldosterone axis.
• GH has a mammotropic effect.
• Factors that stimulate GH secretion include decreased blood glucose and amino acids, starvation, trauma, exercise, testosterone, estrogen, deep sleep, and ghrelin.
• Factors that inhibit GH secretion include increased blood glucose and fatty acids, aging, obesity, exogenous GH, and somatomedins.

Effects of GH

• GH increases RNA and protein synthesis in the Liver.
• GH increases gluconeogenesis, IGFBP and IGFs in the Liver.
• GH increases glucose uptake and lipolysis in adipose tissue while decreasing adiposity.
• GH increases amino acid uptake and protein synthesis in muscle while decreasing glucose uptake and increasing lean body mass.
• GH increases protein synthesis in the kidneys
• GH increases RNA and DNA synthesis in the kidneys, pancreas, and intestines.
• GH increases cell size and number in the intestines and parathyroids.
• GH increases organ size and function in the skin and connective tissue.
• GH increases amino acid uptake and protein synthesis in bone and heart while also increasing collagen and chondroitin sulfate.
• GH stimulates cartilage and bone growth
• Normal growth occurs before the epiphyseal plate disappears.
• GH results in increased protein deposition and reproduction in chondrocytic and osteogenic cells, with chondrocytes converting to osteogenic cells.
• GH strongly stimulates osteoblasts.
• GH stimulates increased deposition of protein by the chondrocytic and osteogenic cells which lead to bone growth
• As a result, the total bone mass and mineral density increase
• GH enhances amino acid transport through cell membranes.
• GH increases nuclear transcription of DNA to form RNA
• GH enhances RNA translation to cause protein synthesis by the ribosomes.
• GH decreases catabolism of proteins and amino acids.
• GH leads to increased mobilization of fatty acids from adipose tissue and increases free fatty acids and ketone bodies in the blood.
• GH promotes increased use of fatty acids for energy
• GH decreases carbohydrate utilization for energy production; it also decreases glucose uptake in tissues, increases glucose production by the liver, and increases insulin secretion.
• GH can have a diabetogenic effect.

Bone Anatomy and Growth

• A growing long bone's ends are called epiphyses, and the remainder is known as the shaft.
• The portion of each epiphysis in contact with the shaft is the epiphyseal growth plate with is actively proliferating cartilage.
• Osteoblasts, the bone-forming cells, convert cartilaginous tissue to bone while chondrocytes lay down new cartilage internally.
• The epiphyseal growth plate remains intact and gradually moves away from the bone shaft's center.
• GH stimulates both osteoblasts and chondrocytes.
• Conversion of Epiphyseal growth plates to bone occurs due to hormonal influences at puberty which results in epiphyseal closure and ends linear growth.
• Bone remodeling involves old bone tissue being replaced by new bone tissue, mainly in the adult skeleton, to maintain bone mass.
• Osteoblasts in the bone periosteum and cavities deposit new bone on older bone surfaces.
• Osteoclasts remove old bone and when the rate of deposition exceeds resorption, bone thickness increases.
• Throughout life, bone continues to thicken under the influence of growth hormone.
• Effects of GH on skeletal results in cartilage and bone growth; normal growth takes place before the epiphysial plate disappears.

GH Related Conditions

• HGH with anti-aging effects have not been supported by research
• Recombinant growth hormone therapy should not be used for elderly patients with normal endocrine function.
• Gigantism refers to an increased release of GH before the closure of the epiphysial plate which results in long length and hyperglycemia.
• Acromegaly occurs during adulthood, causing bones to thicken (especially in the nose, lower jaw, cranium, fingers, and hands).
• Acromegaly leads to changes in the vertebrae which causes a hunched back (kyphosis) with height not extended.
• In Acromegaly soft tissue continues to grow in the liver, kidney, and tongue.
• Acromegaly frequently leads to early death.
• GH hyposecretion can result in panhypopituitarism, failure to pass through puberty, and never secreting sufficient quantities of gonadotropic hormones to develop adult sexual functions.
• GH hyposecretion can also result in dwarfism where all the physical parts of the body develop in appropriate proportion to one another, but the rate of development is greatly decreased.
• GH, adult muscle mass and strength, lean body mass, cardiac function, and bone density can reduce.
• Sometimes the problem relates to somatomedins, so the GH rate is normal, as in the "African pygmy”.