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Endocrine Physiology. Group II. Glucocorticoids-Cortisol. Cortisol (hydrocortisone) is the chief member of the group of hormones known as glucocortiooids which are produced by the zona fasciculata.
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Group II. Glucocorticoids-Cortisol Cortisol (hydrocortisone) is the chief member of the group of hormones known as glucocortiooids which are produced by the zonafasciculata.
These hormones regulate the general metabolism of carbohydrates, proteins and fats on a long-term basis. They play a particularly important role in modifying the metabolism in times of mental and physical stress. Cortisol increases the breakdown of tissue protein to amino acids which are then converted to glycogen in the liver.
The conversion of glucose to glucose-6-phosphate is inhibited. This is the first step in the formation of glycogen from glucose. There is thus a decrease in carbohydrate metabolism and an increase in protein breakdown.
Fat is mobilized from the fat depots, and transported to the liver for conversion into ketone bodies. An excess of cortisol will thus lead to a high blood glucose level and ketosis, i.e, diabetes mellitus. Cortisol impedes the development of cartilage and decreases the absorption of calcium from the intestines by antagonizing vitamin D. Excess cortisol will lead to rarefraction of bones, especially vertebrae.
Cortisol has other actions such as reducing the number of circulating eosinophils. It reduces the allergic response of the body. It reduces inflammation. It has some mineralocorticoid effect. The cortisol production is regulated by ACTH from the anterior pituitary gland (which in turn is probably regulated by ACTH-RF from the hypothalamus).
Like thyroxine, the corticoidsfeed back to the anterior pituitary and inhibit its activity. Thus a high level of blood cortisolreduces the ACTH production by the anterior pituitary. The chief effects of cortisol when given to a patient may be summarized as follows:
1- It increases the use of protein, and decreases the use of carbohydrate for the production of heat and energy. In excess it causes diabetes mellitus. 2- It is anti-inflammatory, that is, it reduces the inflammatory response of the body. 3- It is anti-allergic, that is, it reduces the allergic responses of the-body. 4- It causes some sodium (and hence water) retention.
Synthetic Corticoids Synthetic analogues of cortisol have been made in which one or more of these properties of cortisol predominates. Thus fluorine derivatives such as dexamethasone have been found to have a greatly enhanced anti-inflammatory effect, whilst prednisolone (cortisol with an extra double bond in the ring joined to the oxygen) has very much less sodium retaining properties than cortisol itself.
Group III. Sex Hormones The adrenal cortex is the site of formation of sex hormones: androgens, oestrogens and progesterone. These appear to be relatively unimportantcompared with the sex hormones produced by the gonads. However, tumors of the adrenal cortex may lead to precocious puberty in children, virilism in adult females, and feminization in adult males.
Underactivity of the Adrenal Gland Addison's disease is a generalized underactivity of the whole adrenal gland. If untreated it may be fatal. This disease characterized by: There is muscle weakness, a low blood pressure (B.P. 80/50 is typical), and pigmentation of the skin.
There is an excessive loss of sodium chloride in the urine which leads to a reduction in the tissue fluid and plasma volumes. It is treated by giving sodium chloride and cortisol.
Overactivity of the Adrenal Gland Overactivity of the adrenal cortex leads to Cushing's disease. If it is due to overactivity on the part of the anterior pituitary in producing an excess of ACTH, the condition is termed Cushing's syndrome.
This syndrom characterized by: Retention of sodium which leads to oedema and a high blood pressure (hypertension). The face becomes fat like a full moon (moon-shaped) and the ears are no longer visible when viewed directly from the front.
The breakdown of muscle protein to amino acids leads to wasting and weakness of the skeletal muscles. The skin becomes thin due to the removal of protein and shows purple striations. Diabetes mellitus develops. There is a decrease in the number of circulating eosinophils.
Other changes include abnormal growth of hair on the face, chest and abdomen (hirsutism) and the absence of menstrual periods (amenorrhoea) in the female. All these changes are produced by excessive doses of cortisol.
Pancreas as an Organ of Internal Secretion The islet cells of the pancreas were described by Langerhans in 1869. In 1889 Von Mering and Minkowski demonstrated that the removal of the pancreas in the dog led tosugar appearing in the urine, which is diabetes mellitus.
Early attempts to isolate insulin were unsuccessful because insulin is a protein and is destroyed by the trypsinogen present in the pancreatic juice secreting cells. However, if the pancreatic duct is tied, these cells degenerate and then insulin can be extracted from the gland.
Insulin has been synthesized. It is a protein built up of 51 amino acid units in two coupled chains. Chain A contains 21 amino acid units and has a molecular weight of 2,750. Chain B contains 30 amino acid units and has a molecular weight of 3,700. Insulin is produced by the β-cells of the islet tissue. It is thought to be stored as a zinc compound. Insulin facilitates the entry of glucose into cells.
A deficiency leads to a high blood sugar, fatigue and loss of weight. An excess leads to a low blood sugar, irritability, sweating and a sensation of hunger, and ultimately to coma due to the low blood sugar. Insulin is the antidiabetic hormone and is used to treat diabetes mellitus.
Being a protein it is inactive by mouth and has to be given by injection. It restores the ability to use glucose and fats. The excessive breakdown of proteinceases. The blood glucose level is lowered as the glucose is converted to liver and muscle glycogen and utilized as a source of heat and energy.
The ketosis disappears as the ketone bodies are metabolized in the presence of the carbohydrate metabolism. Glucose and ketone bodiesdisappearfrom the urine.
The physiological importance of a second hormone glucagonproduced by the α-cells of the islet tissue has yet to be evaluated. It raises the blood glucose level probably by mobilizing the liver glycogen in much the same way as does adrenaline.
