Group 5 - Endocrine System - Negative feedback.
E-facilitator - Sophie

Learning outcomes
Describe how hormone physiology is dependent on a negative feedback system.
Present a poster on how the regulation of one hormone is controlled by a negative feedback system eg., using the regulation of the antidiuretic hormone, as an example of how this works.


Intoduction:
The endocrine system is made up of many glands situated around the body. These glands can be either exocrine or endocrine, and secrete hormones. Hormones are chemical messengers that regulate the metabolic function of other cells in the body, causing a variety of effects that usually occur over time. Hormones are either amino acid based or steriod based, and some texts include eicosaniods as well (Marieb, 2007). Hormones are categorised into four groups: polypeptides, glycoprotein’s, amines and steroids. They also can be categorised as either hydrophobic or hydrophilic, which is important in understanding how these messengers regulate their target cells. The primary homeostatic mechanism in this system is called negative feedback, where a variable is kept close to its particular value (Mader, 2007). Most endocrine glands are controlled by the negative feedback system (Marieb, 2007).
boobies.gif
Glands of the endocrine system

Figure 1 (www.hormone.org/endo101/ 2006)

Negative feedback system:
In animals such as ourselves, our bodies must have certain conditions to continue healthy functioning. This is done by a process called negative feedback control, where various receptors and effectors bring about a reaction to ensure that such conditions remain favourable. The sensor detects a change in homeostasis, and relays the data to the control centre. The control centre then releases a negative feedback effect, to return the system to homeostasis (Mader, 2007). It is through this system that the body is able 'to regulate its internal environment [which] is fundamental.' (Marieb, 2004) Negative feedback systems are used to reguate many of the bodys internal workings such as blood pressure, heart rate, levels of oxygen in the blood, minerals, carbon dioxide, body temperature and blood glucose levels as stated in Marieb 2004.

The principle of negative feedback control is illustrated by the simple diagram below:

physio1.gif

This occurrence is known as physiological homeostasis, which basically means a physical equilibrium. It is essentially a corrective mechanism, consider the following scenario in a person:
  • The level of glucose in the bloodstream drops
  • The person requires glucose in cells to meet the demand for ATP
  • The body detects this with a particular receptor designed for this function
  • These receptors release hormones, chemical messages that initiate the start of the feedback mechanism
  • The hormones travel to their target tissue and initiate a corrective response
  • In this case, the corrective response is the secretion of more glucose into the bloodstream

To expand on this example:

The body requires volumes of glucose in order to create ATP. The amount of ATP demanded will fluctuate, and therefore the body regulates the availability of glucose to maximise its energy making potential. Two hormones are responsible for controlling the concentration of glucose in the blood. These are insulin and glucagon. The diagram below illustrates the principle of negative feedback control in action involving blood/sugar levels, notice that it follows the same basic structure as the general principle of negative feedback illustrated above: (biology-online.org 2000)

Neg_feedback_Glucose_example.gif
picture from http://www.biology-online.org/4/2_water_homeostasis.htm


But once the appropriate gland recieves the message that more of a certain hormone is needed how does it know when to stop producing that hormone? This is the key and unique feature of the negative feedback system. Once hormone levels reach their optimum level they serve as a messanger to the receptors and that stops them from transmitting the message to produce more hormones. This is displayed graphically in the animation below:


negfeed.gif
Negative Feedback acting on the Thyroid Gland: picture obtained from http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/basics/control.html
  • Neurons in the hypothalamus secrete thyroid releasing hormone (TRH), which stimulates cells in the anterior pituitary to secrete thyroid-stimulating hormone (TSH).
  • TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect probably all cells in the body.
  • When blood concentrations of thyroid hormones increase above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH. (vivo.colostate.edu 2001)




Positive Feedback
It is also important to note that while negative feedback is a major homeostatic feedback mechanism it is not the only system that links endocrine glands to neural control centres, the other type is called positive feedback, this involves a process in which the end product speeds up its own production, for example the clotting of your blood in response to an injury. When a blood vessel is damaged, structures in the blood called platelets begin to aggregate at the site. Positive feedback occurs as chemicals released by the platelets attract more platelets. The platelet pile then initiates a complex process that seals the wound with a clot. Despite this most endocrine glands are negative feedback controlled. This is because the negative feedback causes deviation from the normal value and when the human body is exposed to a different external stimuli i.e. and increase in temperature, this deviation counters the effect of the external stimuli therefore maintaining homeostasis.


Clinical Applications

In the clinic it is important to possess a basic knowledge of the negative feedback system, this is because many different illnesses or medications can have an effect on hormone production and it is important for those who work in various clinical fields to know how the hormone production is normally regulated to see potential effects of treatment. For example possibly one of the most well known hormone imbalence diseases is diabeties which effects insulin production and regulation. Another condition that may effect the negative feedback loop is depression. The normal negative feedback loop is displayed below:

Adrenalin_production.jpg
(thebrain.mcgill.ca 2007)

"When someone experiences a stressful event, the level of glucocorticoids in their blood rises. Via specific receptors in the hippocampus, this activates the hypothalamus, which then secretes corticotropin-releasing hormone (CRH). The CRH in turn causes the pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream, from which it enters the adrenal glands and causes them to secrete cortisol." (thebrain.mcgill.ca 2007)

This process creates a negative feedback loop in which the excess cortisol activates the brain's glucocorticoid receptors and suppresses the production of CRH. In depressed patients, however, the negative feedback loop no longer works, resulting in excess production of CRH and hence of cortisol. Many seriously depressed patients have high blood levels of cortisol as a result of this breakdown in the negative feedback loop, this is because without the loop when stress occurs the body cannot properly regulate the production of CRH and therefoer cortisol.

Diabetes
Low glucose levels are a good example of how the negative feedback system operates. When glucose levels are too high, the pancreas secretes a hormone called insulin. This hormone stimulates cells to take in glucose until the sugar level returns to normal. When this happen, the pancreas is no longer stimulated and stops secreting insulin (Mader, 2007).
With diabetes, this process is inhibited. There are different types of diabetes, though for this wiki, a general approach will be taken on how this disease effects the clinic situation.

diabetes_type2.jpg
Type II diabetes from soylabs.com, 2006



Conclusion:
Feedback is a regulatory motif common to life at all levels, from the molecular level to the biosphere. Such regulation is an example of the integration that makes living systems much greater than the sum of their parts (Campbell, Reece 2005). Without a system like this the body would not be able to maintain a state of homeostasis and would therefore not be able to function properly. This is because hormone production needs to be regulated; too much or to little of a particular type of hormone can have serious in most cases detrimental effects on the body. Essentially the hormone itself regulates its own concentration in the blood as it serves as a way of lowering the concentration when it gets too high and a lack of it will cause more to be produced, it is in this way that hormone physiology is dependant on negative feedback.




biology-online.org 2000, Homeostasis of Organism Water Regulation, Date Accessed: 28th August 2007 <http://www.biology-online.org/4/2_water_homeostasis.htm>

Campbell, N, Reece, J 2005, Biology, 7th edn, Pearson Benjamin Cummings, USA

Hormone.org 2006, endo 101: the endocrine system, Date accessed: 2nd October 2007 <**www.hormone.org/endo101/**>

Mader, S, Pendarvis, M 2007, Biology, 9th edn, McGraw-Hill Higher Education, Boston

Marieb, E 2007, Human anatomy and physiology, 7th edn, Pearson Benjamin Cummings, USA

Marieb, E 2006, Human anatomy and physiology, 6th edn, Pearson Benjamin Cummings, USA

soylabs.com 2006 Diabetes Date Accessed: 2nd October 2007 <www.soylabs.com/wellness/diabetes.htm>

thebrain.mcgill.ca 2007 SEROTONIN AND OTHER MOLECULES INVOLVED IN DEPRESSION Date accessed: 28th August 2007 <thebrain.mcgill.ca/.../ a_08_m_dep.html>

vivo.colostate.edu 2001 endocrine basics Date accessed: 1st October 2007 <http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/basics/control.html>