INTRODUCTION
The hormone cortisol is essential to health. It is produced by the adrenal glands which sit on top of the kidneys. A lack of cortisol produces exhaustion, chronic fatigue and diseases of the endocrine system such as Addison's disease. Cortisol helps to regulate inflammatory responses in the body as well as balancing blood sugar in times of stress.
EFFECTS
- counteracts insulin
- inhibits IgA in serum
- stimulates gastric-acid and renal-hydrogen ion secretion
- inhibits sodium loss through the small intestine
- moves potassium
- acts as a diuretic hormone
- stimulates many copper enzymes
- can weaken the activity of the immune system
- reduces bone formation
- works with adrenaline to create memories
- additional effects:
- increases blood pressure
- inhibits secretion of CRH
- shuts down the reproductive system
- stimulates hepatic detoxification by inducing tryptophan oxygenase
- similar affinity with aldosterone for the mineralocorticoid receptor
It is commonly produced in higher amounts when stress is present. Recently, a lot of attention has been directed to the effects of excess cortisol. Today, with stress levels being higher than in the past, more people have excess cortisol levels. Lets look at some of the effects of high cortisol.
THE EFFECTS OF EXCESS OF CORTISOL
- Suppress DHEA and PROGESTERONE
- Suppress thyroid activity:
long-term exposure to low levels of thyroid hormones may cause:
- Mobilizes calcium from bones, and circulate it back into blood stream. This means that an excess of cortisol will cause bone loss and therefore osteoporosis.
- Used as a medication, cortisol is given in auto-immune illnesses to suppress the immune system. However, this also means that in a person without these diseases, excess cortisol can suppress the immune system and cause disease. Patients with HIV, Chronic fatigue, candida, parasites, cancer etc. should be aware that if their cortisol elevates, it will worsen their conditions due to immune suppression.
- Induces higher levels of Tryptophan 2,3-dioxygenase (TDO) mRNA expression:
TDO is a first and rate-limiting enzyme for the kynurenine pathway of tryptophan metabolism.
Image Tryptophan metabolism
(Developmental control of messenger RNA for hepatic tryptophan 2,3-dioxygenase)
(Implication of Tryptophan 2,3-Dioxygenase and its Novel Variants in the Hippocampus and Cerebellum During the Developing and Adult Brain)
(Sequence of human tryptophan 2,3-dioxygenase (TDO2): presence of a glucocorticoid response-like element composed of a GTT repeat and an intronic CCCCT repeat)
CANDIDA
Candida and parasites can both be caused by high cortisol for one simple reason: excess cortisol destroys friendly bacteria just like antibiotics do. This will cause the candida and parasites to spread. Cortisol also elevates blood sugar. This means the sugar could feed the candida or even start, or worsen, diabetic conditions. In the case of Oral candidosis we could describe it as one of the side effects of the therapy with inhaled corticosteroids. Candidosis probably occurs because cortisol causes immunosuppression, which interferes with the cell-mediated immunity and causes an increase in the quantity of glucose in the saliva, which, in turn, can stimulate the growth of Candida.
(Prevalence of yeasts in the oral cavity of children treated with inhaled corticosteroids)
(Effects of amphotericin B gargles on oral colonization of Candida albicans in asthmatic patients on steroid inhalation therapy)
BIOCHEMICAL VIEW
- Hyperglycemia
Cortisol counteracts insulin, contributes to hyperglycemia-causing hepatic gluconeogenesis and inhibits the peripheral utilization of glucose (insulin resistance) by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane. However, cortisol increases glycogen synthesis (glycogenesis) in the liver.
- Immunosuppression
Glucocorticoids reduce T cell proliferation and increase T cell apoptosis via mechanisms that are at least partly the result of inhibition of the T cell growth factor, IL-2. Likewise, monocyte apoptosis is increased and influx of other infiltrating inflammatory cells is also repressed. Again, this is partly caused by reduced expression of adhesion molecules, both on migrating and target cells, as well as reduced expression of cytokines and chemokines from sites of inflammation.
Antiinflammatory effects:
- glucocorticoids induce the lipocortin-1 synthesis
- suppress the cyclooxygenase expression
- stimulate the lipocortin-1 escaping to the extracellular space
- release various inflammatory mediators
(Macrophage interaction with Candida albicans in immunodepression)
(Suppression of anti-Candida activity of murine and human neutrophils by glucocorticoids)
RELATIONSHIPS BETWEEN ORAL BONE LOSS AND OSTEOPOROSIS
Osteoporosis is a systemic disease thus it may involve the oral bones as the other sites of the skeleton. From an etiological point of view the osteporosis is classified into two main groups: primary and secondary form. The primary osteoporosis includes postmenopausal classical forms. The secondary form is associated with several diseases (renal, endocrine, gastrointestinal, etc.). or is a consequence of prolonged intake of drugs (steroids, immunosuppressants, anticoagulants, diuretics, anticonvulsants, etc.). Inhaled glucocorticoids are the standard of therapy in asthma and are commonly prescribed for chronic obstructive pulmonary disease. Recent studies have shown that long-term use of inhaled corticosteroid at moderate or high doses is also associated with increased risk for the effects of inhaled corticosteroids on bone.
(Current concepts in corticosteroid-induced bone disease)
(relationship between osteoporosis and alveolar bone loss)
(relationship between periodontal disease and osteoporosis)
MECHANISM OF ACTION:
Glucocorticoids induce rapid bone loss and increase the risk for osteoporotic fractures. The mechanisms include a phase of increased bone resorption, probably a result of the increased expression of receptor activator of nuclear factor-κ-B ligand and colony stimulating factor-1, followed-up by a decrease in bone formation. This effect is central to the actions of glucocorticoids in bone and it is secondary to the loss of bone forming cells, caused by an inhibition of cell differentiation and an increase in the apoptosis of mature osteoblasts and osteocytes. Glucocorticoids also inhibit the function of mature osteoblasts and suppress the synthesis of insulin-like growth factor-I, an agent that enhances bone formation. Glucocorticoids alter the growth hormone/insulin-like growth factor axis in cartilage and, as a consequence, suppress linear growth.
(An anti-inflammatory selective glucocorticoid receptor modulator preserves osteoblast differentiation)
(The protective role of bone morphogenetic protein-8 in the glucocorticoid-induced apoptosis on bone cells)
EFFECT OF LONG TERM CORTICOSTEROIDS ON DENTAL PULP
The various effects of cortisone on dental tissues includes the following: reduction in height of alveolar bone, it becomes osteoporotic with decreased number of osteoblasts, reduction in amount of osteoid matrix and fibrous transformation of periodontal space. It could lead to loss of supporting alveolar bone. Vascular changes in the pulp can be observed, major change being severe dilatation of the vessels.
(Dental Pulpe inflammation)
