Introduction
Endocrinology is the study of the endocrine systems in terms of their hormones and their products, the ductless tissues, and the disorders associated with the hormones (Sastry). Endocrinology is a very wide branch of biology and involves various hormones of the human body and animals. Growth hormone is one of the hormones that fall under the category of hormones discussed in endocrinology. In simpler terms, growth hormone is responsible for growth in human beings and particularly in children although it is also required for fat breakdown and muscle maintenance in adults. Growth hormone is secreted in the anterior pituitary gland and exhibits negative feedback. GH is regulated to keep it at desired levels since deficiency or excess production of the hormone can cause medical conditions such as gigantism in children and acromegaly in adults.
After adolescence, the amount of growth hormone secreted by the body starts to reduce gradually, and by around 60 years, some people no longer secrete growth hormone. This paper will discuss the anatomy and physiology of the pituitary gland which secretes the growth hormone and the pharmacokinetics and Pharmacodynamics of the growth hormone. The paper will also examine how growth hormone is degraded and metabolized as well as the growth hormone receptors and their regulation. In addition, a brief description of diseases or disorders associated with either excess or deficiency of the growth hormone will also be included.
Anatomy and Physiology of the Pituitary Gland
Growth hormone refers to a hormone produced in the pituitary gland and is responsible for the secretion of somatomedin which induces growth. Growth hormone is secreted in the anterior pituitary gland and the cells responsible for its secretion are known as somatotrophs. It induces and accelerates growth in children while it helps in bone mass and muscle building in adults. Acromegaly or gigantism is a condition associated with excess production of the growth hormone (pituitary gland).
The pituitary gland is found at the base of the brain inside the sella tursica bone. Its weight is estimated to be about 0.018 ounces from which the biggest percentage of the composition is water and produces small amounts of hormones daily. The pituitary gland is divided into two major sections known as the anterior and posterior pituitary glands. More often than not, the pituitary gland is referred to as the master gland due to its major roles in the body though this is a misconception since most of its function is regulated (pituitary gland). Most of the hormones produced in the pituitary gland are secreted in the hypothalamus but the pituitary gland takes over when it comes to their release.
As such, it would be correct to state that the pituitary gland works hand in hand with the hypothalamus. Hypothalamus uses the nerve fibers’ and minute capillaries to send signals to the posterior pituitary and anterior pituitary glands respectively. The hypothalamus is responsible for sending body messages to the pituitary gland about hormonal information and pain among others. The anterior pituitary gland is responsible for the secretion of seven hormones namely: growth hormone (GH), follicle-stimulating hormone (FSH), adrenal corticotrophic hormone (ACTH), prolactin, luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and melanocyte-stimulating hormone (MSH) (pituitary gland).
Hormones secreted by the anterior pituitary gland have different functions in the body. Growth hormone stimulates the influx and size of the body cells responsible for stimulating growth and reproduction. Growth hormone performs various functions such as reducing carbohydrate utilization to raise blood sugar levels, aiding in muscle growth and maintenance, helping in protein synthesis, and helping the body in consuming excess fat stores.GH boosts the body’s immune system and is very essential when it comes to tissue repair. Many adults of about fifty years old no longer secrete the growth hormone. Thyroid-stimulating hormone is responsible for the secretion of triiodothyronine and thyroxine.
TSH determines the amount and the size of thyroid cells in the body. Excess levels of thyroid-stimulating hormone in the body are a result of either very low temperatures or emotional trauma (Dr.springers,1999). Luteinizing hormone aids in the production of reproductive hormones. The hormone helps in the growth and development of some reproductive organs such as testosterone in males and follicle tissues in women. It also aids in the secretion of progesterone and estrogen in female bodies. Follicle-stimulating hormone aids in estrogen synthesis and is responsible for the formation and development of sperms and ovules in both men and women respectively.
The adrenal corticotrophic hormone is responsible for the secretion of cortisol and can influence its secretion by up to 2000%. ATC is affected by factors and conditions such as chronic diseases, surgery, extreme low or high temperatures among others. Melanocyte stimulating hormone is responsible for skin color and aids in maintaining memory and eyesight. Last but not the list is the prolactin hormone which stimulates the mammary gland cells during pregnancy (Dr.springers, 1999).
Prolactin is not secreted in the body until a woman is pregnant to help in the synthesis of fat, casein, and lactose which are responsible for milk production. It is also responsible for the increase in breasts size during pregnancy. Antidiuretic hormone (ADH) and oxytocin are produced in the posterior pituitary gland. Oxytocin is secreted when a woman is about to give birth and it is responsible for labor pains during delivery and transportation of milk to the ducts from the alveoli. ADH helps the kidneys retain water and electrolytes. It is important to note that both oxytocin and antidiuretic hormones are secreted by the hypothalamus and housed by the posterior pituitary gland (Dr.springers, 1999).
Pharmacodynamics and pharmacokinetics of growth hormone
Growth hormone is one of the endocrine glands and it is estimated to have about 191 amino acids which are protein in nature. Amino acids are claimed to aid in increasing the amount of growth hormone secreted by the body. Generally, hormones are found in interstitial and plasma tissues in low levels that range between 10-7M and 10-10M. Due to these low levels of hormones, sensitive protein receptors have come up to improve the situation by sensing extremely weak signals (Artwelle et.al. 2008).
Production of excess hormones in the body would also be detrimental causing disorders and illness hence the reason systemic feedback mechanisms have been devised to aid in controlling the production of the hormones. All endocrine glands are bound by a particular plasma protein carrier and their secretions are carried to distant tissues other than where they were secreted. Growth hormone is one of the endocrine glands with peptide carrier proteins whose role is to protect the hormone from being destroyed by plasma proteases (Artwelle et.al. 2008).
Metabolism of growth hormone
Metabolism is defined as the chemical breakdown of a food substance into a simpler form to make it available to the body. Growth hormone does not only cause growth but is also important in metabolism. Growth hormones help in protein metabolism, carbohydrate metabolism, and fats metabolism and thus plays a role in transferring molecules, Breaking down fats, energy conservation, and protein synthesis (Human Growth Hormone: Metabolism with the Help of Human Growth Hormone).
Protein metabolism is a process that entails protein breakdown and helps in separating useful products from waste. Thus the hormone stimulates protein anabolism which aids absorption of amino acids, manufacture, and oxidation of the proteins. Growth hormone accelerates the breakdown of triglyceride and the oxidation of adipocytes. Glucose is broken down through a process known as carbohydrate metabolism and GH plays an important role in the same.
The end product of carbohydrate metabolism is energy which is utilized by the body. The rate at which growth hormone is transferred to the target tissues is determined by various factors one of them being that it is bound by the protein. The hormone becomes available to the tissues only after it disintegrates from though binding protein (Human Growth Hormone: Metabolism with the Help of Human Growth Hormone).
Growth Hormone Half-Life
High levels of Growth hormone are experienced in childhood and adolescence after which the levels dwindle with maturity. There are various forms of growth hormone secreted by the pituitary gland. The most common ones are 22 kDa GH (191 amino acids) and 20 kDa GH whose residue amino acids are less by fourteen. The 191 amino acid form of growth hormone has a half-life of about 18 minutes (Artwelle et.al. 2008). The hormone is cleared from the body during its dissemination to the tissues.
Regulation of growth hormone secretion
Hypothalamus regulates the amount of growth hormone in the body via negative feedback. Negative feedback implies that an opposite or counter-action is taken to regulate the levels of the hormone. It is important to note that all the endocrine hormones are regulated through negative feedback. Low levels of growth hormone are countered by the release of the growth hormone-releasing (GH-RH) hormone by the hypothalamus. On the other hand, high levels are countered by the secretion of somatostatin by the hypothalamus inhibits the further secretion of GH (Hossner, 2005).
Several hormones are involved in the regulation of growth hormone and some of them include; growth hormone-releasing hormone (somatocrinin), somatostatin, and ghrelin. Growth hormone-releasing hormone is a peptide in nature secreted by the hypothalamus and consists of 44 amino acids. It stimulates the release of growth hormone when it binds with particular receptors located on the anterior pituitary somatotrophs. Somatostatin is produced in several body tissues which include but are not limited to; the hypothalamus, intestinal tract, and pancreas (Hossner, 2005).
The role of somatostatin in regulating growth hormone is to impair or inhibit its release. If there is excess secretion and release of growth hormone, somatostatin counters this by ensuring that the levels of the hormone released are cut down. It plays a part in inhibiting the release of several growth hormones. Last but not least is the Ghrelin. Ghrelin is produced in the stomach and works together with somatostatin and growth hormone-releasing hormone to accelerate the secretion of growth hormone. Growth hormone secretagogue receptor (GHS-R) is a ghrelin receptor found in cells in the anterior pituitary gland and is the one that combines with the others to stimulate secretion of the growth hormone (Hossner, 2005).
The growth hormone receptor is a cytokine in nature and falls under the same category as prolactin receptors and interleukins. Pfaff, (2002) States that “the human GH-R gene was cloned in 1987 by Leung et al. it is a protein of 620 amino acids, consists of 10 exons and spans 87kb (Godowsky et al, 1989). Exons 2-7 encode the extracellular domain (246 residues), exon 8 the single membrane-spanning domain (23 residues), and exons 9-10 the intracellular (cytoplasmic) domain (351 residues) (Godowski et al., 1989). The extracellular domain is identical to GH binding protein in structure. The human GH-R gene is located on the short arm of chromosome 5p13.1.” ordinarily, cytokine exists as single polypeptide monomers but they form dimers after they are activated by binding hormones. The formation of dimmers stimulates cytoplasmic Janus kinase which in return phosphorylates proteins into a serine/ threonine kinase (Hossner, 2005).
Growth Hormone Conditions
Growth hormone is associated with certain conditions that result from either having excess growth hormones in the body or less. Two conditions associated with excessive secretion of growth hormone are gigantism in children and acromegaly in adults. Gigantism is a very rare condition that reduces life expectancy and it’s caused by somatotrophs tumor. On the other hand, acromegaly is associated with excessive secretion of GH hormone in adults and it occurs in a gradual manner such that it is not discovered in the early stages. It is linked to pituitary tumors and some of the symptoms are swelling of the soft tissues and cardiac diseases among others.
Deficiency in growth hormone often happens in adults. Adults need growth hormone though in smaller dosages as compared to children to enhance brain function, bone and muscle maintenance as well as lipid breakdown to release energy. This condition occurs when either the pituitary gland or hypothalamus is injured or damaged. Generally, tumors and surgeries are blamed for damages to the pituitary or the hypothalamus. The following is a list of symptoms likely to be exhibited by adults suffering from a deficiency in growth hormone.
Depression or anxiety, excess fat deposits around the waist, fatigue, reduced libido, loneliness, lean body mass, general body weakness, and increased bone fractures as age caught up with them( Cedars-Sinai: Adult Growth Hormone Deficiency). Growth hormone deficiency can be corrected or stabilized using recombinant DNA technology. This technology has made treatment of the condition cheaper and easier. However, it has been noted that most people such as athletes use it to accelerate healing whenever they have muscle injury (Vedamurthy, 2003). Precaution needs to be taken since it can result in adverse effects reversing the situation to either gigantism or acromegaly depending on the age.
Conclusion
Growth hormone is a peptide produced in the anterior pituitary gland ad contains 191 amino acids. The pituitary gland is divided into the anterior pituitary gland and posterior pituitary gland. The anterior pituitary gland is responsible for the production of seven major endocrine hormones namely; growth hormone, luteinizing hormone, follicle-stimulating hormone, prolactin, adrenal corticotrophic hormone, thyroid-stimulating hormone, and melanocyte-stimulating hormone. Posterior pituitary gland secretes two hormones; antidiuretic hormone (ADH) and oxytocin. Growth hormones help in protein metabolism, carbohydrate metabolism, and fat metabolism.
The hormone has a half-life of about 20 minutes and it is cleared from the body during its dissemination to the necessary tissues as is the case with all other hormones. The hormone is regulated through negative feedback and the main regulating hormones are; growth hormone regulating hormone, somatostatin, and ghrelin. The growth hormone receptor is a single polypeptide monomer that falls in the family cytokine and forms dimmers after activation by binding protein. Excess growth secretion of growth hormone leads to a condition known as gigantism in children and acromegaly in adults.
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