This website was developed by undergraduate biology researchers working with Dr. Karen Bernd at Davidson College.

Effects of Metabolism

General Research Question

I am examining how metabolism affects lung cells' ability to protect against and recover from ozone induced oxidative damage.

General Background on Metabolism

When people hear the term ‘Metabolism,’ they often think of a 'thin' person that can eat constantly but never gain weight. The science of metabolism explains how this might happen. At the cellular level metabolism is the sum of all chemical reactions involved in the storage or use of energy (Marieb, 2008).  Reactive oxygen species (ROS) are byproducts of metabolism, especially cellular respiration.  While cells require low levels of ROS, high concentrations of the oxidants are toxic (Poncin, 2007). This means that the concentration of ROS must be controlled so that cells stay in the 'healthy' range and prevent damage to their components. Mechanisms must exist to reduce the threat of damage to cells that are exposed (temporarily or long term) to oxidants that they produce or that are found in their environment. My research is interested in what those mechanisms are and if they could be manipulated to help protect the lungs of people with increased exposure to oxidants.

One way to increase a lung cell's exposure to oxidants is exercise. When we exercise, we not only increase the amount of air we breathe in and therefore increase our lungs' exposure to air pollutants, such as ozone, but we also increase our metabolic rate and therefore increase our generation of ROS. Learn more about ROS, check out our ROS page. To mimic these conditions using lung cells grown in culture (in petri plates) we can change ozone exposure in an ozone exposure chamber and vary metabolic rate using thyroid hormone.

Major Players in Metabolism

An individual’s basal metabolic rate is highly regulated by the thyroid gland through the secretion of thyroid hormone (TH). TH is used to refer to two similar molecules, thyroxin (T4) and triiodothyronine (T3). In the Bernd lab we have shown that lung cells grown in high T3 levels consume more glucose from the growth media-- indicating that they have a higher metabolic rate.  In the body, the thyroid’s secretion of TH is in turn regulated by the body’s concentration of thyroid stimulating hormone (TSH) as part of a negative feedback loop with the hypothalamus

Thyroid Gland
 
Main Role:
Regulation of the body's basal metabolic rate through the secretion of thyroid hormones (TH).
 
Biological System: Endocrine System
 
Location: Bi-lobed structure (structure resembles a butterfly) located on ventricular surface of trachea
 
Regulation: The thyroid's production and secretion of TH is increased by thyroid-stimulating hormone (TSH), a hormone produced by the anterior pituitary.  TSH in turn is regulated by thyrotropin-releasing hormone (TRH).  High concentrations of TH in the blood inhibit the secretion of TRH and TSH, creating a negative feedback loop and thereby causing concentration of TH in the blood to return to normal.
 
Hormones:
-Thyroid Hormones: Thyroxine (T4) & Triiodothyronine (T3)
-Calcitonin: decreases serum calcium concentration (Thyroid C cells)

Thyroid Hormones: Triiodothyronine (T3) & Thyroxine (T4)
 
Main Role:
To increase the body's basal metabolic rate by affecting many target cells throughout the body (Marieb et al., 759).
 
Location: Made and released from Thyroid Gland, circulates in blood
 
Hormone Class: Modified amino acid (tyrosine)
 
Other information: Overproduction or underproduction of TH can affect a person's activity level as seen in the case of hyper- and hypothyroidism. To learn more about these conditions, see below.

Anterior Pituitary Gland (Adenohypophysis)
 
Main Role:
Helps to regulate several bodily functions such as reproduction, growth and stress through the secretion of several hormones.
 
Biological System: Endocrine System
 
Location: The pituitary gland is a small, tri-lobed gland located at the base of the brain. The two main lobes, the anterior and posterior lobes, both have their own set of distinct functions.
 
Regulation: The anterior pituitary gland's hormonal secretions is regulated by releasing/inhibiting hormones secreted be the hypothalamus. In the case of thyroid-stimulating hormone (TSH), the particular hormone we are looking at here, TSH secretion by the anterior pituitary is regulated by is regulated by thyrotropin releasing hormone (TRH) as part of a negative feedback loop.
 
Hormones:
Tropic Hormones (hormones that stimulate other endocrine glands to release hormones):
-Thyroid-stimulating hormone (TSH)
-Adrenocorticotropic hormone (ACTH)
-Luteinizing hormone (LH)
-Follicle-stimulating hormone (FSH)
-Thyroid-stimulating hormone (TSH)
 
Direct Hormones
-Prolactin
-Endorphin
-Growth hormone

Thyroid Stimulating Hormone (TSH)
 
Main Role:
Regulation of the thyroid gland's secretion of TH.
 
Gland: Pituitary Gland (Anterior)
 
Location: The pituitary gland is a small, tri-lobed gland located at the base of the brain. The two main lobes, the anterior and posterior lobes, both have their own set of distinct functions.
 
Hormone Class: Peptide

Related Disorders

Thyroid Disorders:

Hyperthyroidism

General:
Term refers to any condition involving excess thyroid hormone levels, usually due to an overactive thyroid gland.  Since thyroid hormones typically control the rate of all bodily processes, too much thyroid hormone causes all these functions to speed up, as seen in many of the symptoms (American Thyroid Association, 2005 A).

Common Causes:

Prevalence:

  • Between 1988 and 1994, an estimated 1.3% of the total United States population had hyperthyroidism (2,610,097 people) (Hollowell et al., 2002)
  • Study also found that many thyroid dysfunctions go unrecognized and that frequencies varied among different racial/ ethnic groups (Hollowell et al., 2002)
  • Graves' disease affects 1 out of every 20 women overall (Marieb et al., 2008)
    • Most common in middle aged women
  • Due to all of the hormonal changes that occur during pregnancy, pregnant women have an increased chance of developing maternal hyperthyroidism (American Thyroid Association, 2005 D).
    • Graves’ disease is the most common cause (80-85%) of maternal hyperthyroidism, occurring in 1 out of 1500 pregnant mothers
    • For more information about thyroid disease and pregnancy, click here

Types:

  • Graves' Disease
    • Most common form of hyperthyroidism
    • Immune system produces abnormal antibodies that imitate thyroid stimulating hormone (TSH) by binding to the surface of thyroid cells, triggering them to over secret thyroid hormones (see figure 1). This leads to an overactive thyroid (American Thyroid Association, 2005 B).
    • Main symptoms
      • Inflammation and bulging of the eyes (Graves’ ophthalmopathy, see figure 2) (American Thyroid Association, 2005 B).
      • Other symptoms are typically the same as those seen in other types of hyperthyroidism
    • To learn more about Graves’ Disease, click here
  • Toxic Nodular or Multinodular Goiter
    • Also common with hypothyroidism, for more information see below
  • Thyroiditis

 

Symptoms:(American Thyroid Association, 2005 A)

  • Elevated metabolic rate
  • Rapid heart rate
  • Increased perspiration
  • Hand tremors
  • Nervousness/Anxiety
  • Difficulty sleeping
  • Thinning of skin and hair
  • Muscular weakness
  • Weight loss despite regular food intake
  • Continual warm feeling


Image from http://emedicine.medscape.com/article/120619-overview
 
Figure 2. Varying degrees of Graves' Ophthalmopathy. Bulging of the eyes as a result of Graves' disease, the most common type of hyperthyroidism.

Hypothyroidism

General:
Condition caused by an insufficient amount of thyroid hormone in the blood stream due to an underactive thyroid gland (American Thyroid Association, 2005 C). Since thyroid hormone increases the body's basal metabolic rate, low levels of thyroid hormone means the cells are unable to increase their metabolic rates, which causes all of the all bodily processes to slow down, as seen in many of the symptoms (American Thyroid Association, 2005 C).

Common Causes: (American Thyroid Association, 2005 C; Marieb et al., 2008)

  • Auto immune disease
  • Surgical removal of the thyroid
  • Radiation treatment
  • Iodine deficient diet (Endemic goiter)

Prevalence:

  • Between 1988 and 1994, an estimated 4.6 % of the total United States population had hypothyroidism (9,597,742 people) (Hollowell et al., 2002)
  • Due to all of the hormonal changes that occur during pregnancy, pregnant women also have an increased chance of developing maternal hypothyroidism (American Thyroid Association, 2005 D)
  • For more information about thyroid disease and pregnancy, click here
    • For more information about thyroid disease and pregnancy, click here

Types:

  • Adult Hypothyroidism/ Myxedema
    • Result of hypothyroidism in adults
    • Usually an autoimmune disease that causes antibodies to attack and destroy thyroid tissue
    • In addition to the symptoms listed above, symptoms might include puffy eyes, edema and mental sluggishness (not due to mental retardation)
  • Cretinism
    • The form of hypothyroidism expressed in children
    • Common characteristics can include a “short, disproportionate body, a thick tongue and neck, and mental retardation” (Marieb et al., 2008)
  • Endemic goiter (see figure 3)
    • Visible lump on the front of the neck caused by an enlarged thyroid gland due to an iodine-deficient diet

 

Symptoms: Insufficient levels of thyroid hormone causes different effects depending on the age of the individual (Marieb et al., 2008). These are some of the more general symptoms (American Thyroid Association, 2005 C):

  • Constant chilliness
  • Lethargy
  • Skin dries out
  • Increased forgetfulness and depression
  • Constipation
  • Weight Gain

 


Image from http://www.mayoclinic.com/health/goiter/DS00217
 
Figure 3. Pictorial representation of a goiter, a large lump on the front of the neck, which results from the thyroid gland enlarging past its normal size (outline).

Additional Information on Thyroid Related Disorders

 

Related Lung Disorders

Exercise-Induced Bronchoconstriction (EIB)/ Exercise-Induced Asthma (EIA)

General: Asthma is a reversible obstructive lung disease caused by hypersensitivity of the bronchial tubes to various stimuli, such as exercise in the case of exercise-induced asthma (EIA) (American Lung Association, 2010).  This hypersensitivity results in chronic inflammation of the bronchial tubes causing them to swell and therefore narrow the airways, making it harder to breath.  In addition to the continuous underlying inflammation, asthma is characterized by acute exacerbations, usually referred to as ‘asthma attacks’ or ‘episodes’ (American Lung Association, 2010; see figure 4).  Episodes are the result of a series of events, such as swelling of the lining, tightening of surrounding muscles, and increased secretion of mucus, all of which result in constricted airways and difficulty breathing (American Lung Association, 2010).

Potential Triggers of Asthma: (American Lung Association, 2010)

  • Excercise
  • Outdoor and indoor air pollutants, including ozone and particle pollution
  • Excitement or stress
  • Smoke from cigarettes
  • Respiratory infections and colds
  • Allergic reactions to certain allergens
  • Exposure to cold air or sudden temperature change

Prevalence: (American Lung Association, 2010)

  • An estimated 23.3 million Americans had asthma in 2008
  • Out of those 23.3 million, 12.7 million had an asthma attack
    • 4.1 million were children under the age of 18

 

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