THE ENDOCRINE SYSTEM 



619 



F). The most potent mineralocorticoid is aldosterone, discovered in 

 1953; desoxycorticosterone is an effective regulator of salt and water 

 metabolism and is widely used clinically. Adrenosterone and dehydro- 

 epiandrosterone are typical adrenal androgens. 



Experiments on the biosynthesis of steroids have shown that they 

 are made by the union of two-carbon acetyl coenzyme A units to form 

 cholesterol. The cholesterol content of the adrenal cortex exceeds that 

 of any other organ; as much as 5 per cent of the wet weight of the 

 gland may be cholesterol. Steroids are synthesized from cholesterol not 

 only in the adrenal cortex but in the testis, ovary and placenta as well. 

 The synthetic pathways of these compounds are interrelated; proges- 

 terone, for example, appears to be the precursor of both aldosterone 

 and hydrocortisone in the adrenal cortex and of testosterone and es- 

 tradiol as well. The hormones produced by each of these organs are 

 summarized in Table 8. 



The complete removal of the adrenal cortex, or its hypofunction 

 in Addison's disease, results in an increased excretion of sodium in 

 the urine and a corresponding excretion of chloride, bicarbonate and 

 water. The loss of sodium produces an acidosis, and the loss of body 

 fluid leads to lowered blood pressure and a decreased rate of blood 

 flow. The concentration of potassium in the blood increases. There is a 

 marked decline in blood sugar concentration and in the glycogen con- 

 tent of liver, muscle and other tissues. It is clear from experimental 

 evidence that the animal's ability to produce carbohydrates from pro- 

 teins is greatly impaired. 



The appetite for food and water decreases and there is loss of 

 weight. There are marked upsets in the digestive tract, with diarrhea, 

 vomiting and pain. Muscles are more readily fatigued, and less able 

 to do work. The basal metabolic rate decreases and the animal is less 

 able to withstand exposure to cold and other stresses. Death ensues 

 within a few days after complete adrenalectomy. The skin of a patient 

 with Addison's disease develops a peculiar bronzing in patches, owing 

 to the deposition of melanin. 



Hydrocortisone and cortisone have marked effects in inhibiting 

 hypersensitivity, allergies, and inflammation in tissues, presumably by 

 modifying the reactivity of mesenchymal tissue. They also inhibit the 

 proliferation of tissues in the joints of persons suffering from rheuma- 

 toid arthritis. The two hormones are widely used clinically in the treat- 

 ment of these conditions. 



Enlargement of the adrenal cortex and hypersecretion of adrenal 



Toble 8. STEROID HORMONES 



ADRENAL CORTEX 



OVARV 



Hydrocortisone 



Desoxycorticosterone 



Aldosterone 



Androstereone 



Dehydroepiandrosterone 



Estradiol 



Estradiol 



Progesterone 



Androgens 



TESTIS 



Testosterone 



Androstenedione 



Estradiol 



Estrone 



Corticoids 



PLACENTA 



Progesterone 

 Estradiol 

 Androgens?? 

 Corticoids 



