Monday 24 September 2012

Growth Hormone

Hello :) In this post we'll explore the regulation of growth hormone (GH) secretion, the association between GH and somatomedins (IGFs) and their effects on body growth and metabolism. We'll also take a look a the major abnormalities associated with abnormal GH secretion. Finally, I'll explain why growth hormone has been used in production animals and describe the importance of ghrelin in GH secretion. Enjoy!

Effects on Growth and Metabolism

GH is a peptide hormone which is synthesised by the somatotrope cells in the anterior pituitary and has several effects on the body.

Growth - Indirect Anabolic Effects:

The indirect growth effects of GH are mediated by somatomedins (insulin-like growth factors). GH stimulates the liver to produce IGFs which act as "classical hormones", while others IGFs produced in other parts of the body work locally as paracrines. IGFs are very important and mediate cell growth and proliferation in most cells but its major target is bone and muscle. 

GH causes new bone to be laid by osteoblasts on the outer surface while bone is resorbed by osteoclasts on the inner circumference of bones. This causes the bone circumference to increase with a simultaneous increase in the diameter of the marrow cavity while the weight of the bone remains the same. GH also causes the addition of new bone at the epiphyseal plates of bones. In this process, new cartilage is deposited and then is converted to new bone.

GH also causes an increased cellular uptake of amino acids for protein synthesis as well as a decreased rate of protein breakdown from muscle. It also causes increased cell size (hypertrophy) and proliferation (hyperplasia). 

Metabolism - Direct Catabolic Effects

GH acts an antagonist to insulin and causes a decrease in the uptake of glucose by adipose and muscle cells. It also causes an increase in glucose production by the liver through gluconeogenesis (see this post). Overall it is diabetogenic, that is it increases plasma glucose concentrations.

Growth Hormone also has an effect on lipids by activating hormone sensitive lipase resulting in an increase in lipolysis (see this post). This causes increased fat metabolism and a decrease in fat deposition and the use of fats as energy in order to conserve glucose is encouraged. Overall, GH causes an increased concentration of plasma fatty acid concentrations.   


Regulation

The secretion of GH is under dual regulation by the hypothalamus:
  1. GH Releasing Hormone (GHRH): this binds to the GHRH receptor and stimulates GH synthesis and secretion. The release of GHRH is pulsatile, thus GH release is also pulsatile. 
  2. Somatostatin (SS) or Growth Hormone Inhibiting Hormone (GHIH): this is a potent inhibitor of GH release but has no effect on synthesis. The secretion of SS increases with a rise in GH or IGF-1 (insulin-like growth factor 1)
GH follows a daily cycle as well as lifetime secretory patterns. Daily, secretion follows circadian rhythms where there is increased secretion at night, peaking at early morning. The pulsatile secretion is due to the pulsatile release of GHRH from the hypothalamus. Over the course of an animal's life, there is an increased release of GH as a neonate and at puberty while secretion decreases with older age.   

 IGF-1 is a major determinant of negative feedback control as an increase in insulin-like growth factor secretion results in a decrease in GHRH secretion and an increase in SS secretion. In addition, hypoglycaemia, decreased plasma fatty acids and amino acids will result in an increase in GH secretion. Stress, circadian rhythms, sleep and ghrelin also causes an increase in GH secretion. 

Ghrelin

Ghrelin is secreted mainly by the stomach and is the hormone of hunger as its concentration increases before meals and decreases afterwards. Ghrelin binds to the GH secretagogue receptor (GHSR) and this induces the synthesis and secretion of GH from the pituitary.  

Abnormalities

Pituitary Dwarfism 

This is a congenital deficiency of GH (which leads to low IGF-1 levels which cause the ineffective growth of bones and muscles). Clinical signs include short stature, bone deformities and well as a variety of endocrine related coat and skin problems. It seems that German Shepherd dogs are predisposed to this condition. 

Gigantism:

This isn't reported in animals but does occur in humans. It occurs because of an excess secretion of GH before the epiphyseal plates close and results in an abnormally large stature, but in proportion. Associated problems include cardiac hypertrophy, glucose intolerance, hyperinsulinaemia, and premature death. 

Acromegaly:

This causes enlarged extremities because excessive GH secretion occurs after the epiphyseal plates close. This results in the growth of soft tissue and an increase in bone circumference. This condition is mostly seen in cats due to chronic pituitary neoplasia (the abnormal proliferation of cells) which causes:
  • increased size of the head, feet and abdomen
  • organ hypertrophy
  • diabetogenic effects
  • insulin-resistant diabetes mellitus. 
The Use of Growth Hormones in Production Animals 

Growth hormones are species specific and pharmacologic administration of GH leads to:
  • increased feed efficiency
  • improved muscle mass
  • reduced carcass lipid content
  • increased carcass protein content
  • increased milk production (by up to 10-40%)

That's all for this post, if you have any questions please feel free to ask in the comments section below :)


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