Human growth hormone

SIGNIFICANCE:Human growth hormone (HGH) determines a person’s height, and abnormalities in the amount of HGH in a person’s body may cause conditions such as dwarfism, giantism, and acromegaly. Genetic research has led to the means to manufacture enough HGH to correct such problems and expand the understanding of HGH action and endocrinology.

Growth Hormones and Disease Symptoms

The pituitary (hypophysis) is an acorn-sized gland located at the base of the brain that makes important hormones and disseminates stored hypothalamic hormones. The hypothalamus controls the activity of the pituitary gland by sending signals along a network of blood vessels and nerves that connects them. The main portion of the pituitary gland, the adenohypophysis, makes six trophic hormones that control many body processes by causing other endocrine glands to produce hormones. The neurohypophysis, the remainder of the pituitary, stores two hypothalamic hormones for dissemination.

Dwarfism is caused by the inability to produce growth hormone. When humans lack only human growth hormone (HGH), resultant dwarfs have normal to superior intelligence. However, if the pituitary gland is surgically removed (hypophysectomy), the absence of other pituitary hormones causes additional mental and gender problems. The symptoms of are inability to grow at a normal rate or attain adult size. Many dwarfs are two to three feet tall. In contrast, some giants have reached heights of more than eight feet. The advent of gigantism often begins with babies born with pituitary tumors that cause the production of too much HGH, resulting in continued excess growth. People who begin oversecreting HGH as adults (also caused by tumors) do not grow taller. However, the bones in their feet, hands, skull, and brow ridges overgrow, causing disfigurement and pain, a condition known as acromegaly.

Dwarfism that is uncomplicated by the absence of other pituitary hormones is treated with growth hormone injections. Humans undergoing such therapy can be treated with growth hormones from humans or primates. Growth hormone from all species is a protein made of approximately two hundred amino acids strung into a chain of complex shape. However, differences in amino acids and chain arrangement in different species cause shape differences; therefore, growth hormone used for treatment must be extracted from a related species. Treatment for acromegaly and gigantism involves the removal of the tumor. In cases where it is necessary to remove the entire pituitary gland, other hormones must be given in addition to HGH. Their replacement is relatively simple. Such hormones usually come from animals. For many years, the sole source of HGH was pituitaries donated to science. This provided the ability to treat fewer than one thousand individuals per year. Molecular genetics has solved that problem by devising the means to manufacture large amounts of transgenic HGH.

Growth Hormone Operation and Genetics

In the mid-1940s, growth hormone was isolated and used to explain why pituitary extracts increase growth. One process associated with HGH action involves cartilage cells at the ends of long bones (such as those in arms and legs). HGH injection causes these epiphysial plate cells (EPCs) to rapidly reproduce and stack up. The EPCs then die and leave a layer of protein, which becomes bone. From this it has been concluded that growth hormone acts to cause all body bones to grow until adult size is reached. It is unclear why animals and humans from one family exhibit adult size variation. The differences are thought to be genetic and related to production and cooperation of HGH, other hormones, and growth factors.

Genetic research has produced transgenic HGH in bacteria through the use of technology. The gene that codes for HGH is spliced into a special circular piece of DNA called a expression vector, thus producing a recombinant expression vector. This recombinant is then put into bacterial cells, where the bacteria express the HGH gene. These transgenic bacteria can then be grown on an industrial scale. After bacterial growth ends, a huge number of cells are harvested and HGH is isolated. This method enables isolation of enough HGH to treat anyone who needs it.

Impact and Applications

One use of transgenic HGH is the treatment of acromegaly, dwarfism, and gigantism. The availability of large quantities of HGH has also led to other biomedical advances in growth and endocrinology. For example, growth hormone does not affect EPCs in tissue culture. Ensuing research, first with animal growth hormone and later with HGH, uncovered the EPC stimulant somatomedin. Somatomedin stimulates growth in other tissues as well and belongs to a protein group called insulin-like growth factors. Many researchers have concluded that the small size of women compared to men is caused by estrogen-diminished somatomedin action on EPCs. Estrogen, however, stimulates female reproductive system growth by interacting with other insulin-like growth factors.

Another interesting experiment involving HGH and genetic engineering is the production of rat-sized mice. This venture, accomplished by putting the HGH gene into a mouse chromosome, has important implications for understanding such mysteries as the basis for species specificity of growth hormones and maximum size control for all organisms. Hence, experiments with HGH and advancements in genetic engineering technology have led to, and should continue to lead to, valuable insights into the study of growth and other aspects of life science.

Over the years, HGH has also been abused by celebrities, athletes, and other individuals hoping to slow the aging process or help build muscle. Despite a lack of evidence and debate within the medical community about the actual effects that HGH has as an antiaging method or performance enhancer, people have purchased pills or received injections of HGH in an attempt to achieve these goals. The National Football League (NFL) had banned the use of HGH in 1991 but did not begin testing for it until 2014, amongst fears that athletes may be combining HGH with the use of steroids. Researchers have also expressed concern about the long-term risks believed to be associated with continued use, such as increased risks of cancer, heart failure, and diabetes.

In the early 2020s, HGH was shown to have a positive effect on the symptoms of long COVID-19, with some patients showing significant improvement in neurological symptoms. At the same time, studies were underway to determine HGH's role in Alzheimer's disease, especially after some British children treated for growth deficiencies with HGH harvested from cadavers developed Alzheimer's. In addition, families of patients who needed HGH for growth issues and conditions such as Prader-Willi syndrome were experiencing frustration due to a shortage of HGH.

Key Terms

• endocrine glanda gland that secretes hormones into the circulatory system
• hypophysectomysurgical removal of the pituitary gland
• pituitary glandan endocrine gland located at the base of the brain; also called the hypophysis
• transgenic proteina protein produced by an organism using a gene that was derived from another organism

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