Adrenal cortical hormones synthesis

In the animal body three important groups of hormones are formed by the metabolism of cholesterol the progestins, the sex hormones, and the adrenal cortical hormones 249 Their synthesis occurs principally in mitochondria of the adrenal cortex and the gonads. Steroid hormone synthesis is regulated by hormones, such as corticotropin (ACTH), from the anterior pituitary250 (see Chapter 30) and is also dependent upon the recently discovered steroidogenic acute regulatory protein, which in some way promotes the movement of stored cholesterol into mitochondrial membranes.251 252 Some major pathways of... 

When Long and his colleagues (Sayers et al., 1944) first observed the fall in adrenal ascorbic acid and cholesterol that followed the injection of ACTH, they rightly suggested that the two processes may be related to cortical hormone synthesis in, or release from, the adrenal gland. There is still no reason to doubt this opinion however, the further idea that ascorbic acid facilitaies the synthesis of cortical hormones is not supported by recent evidence. 

In the same year that he identified carbon suboxide, Diels began to investigate cholesterol with E. Abderhalden. The structure of this Hpid had not yet been determined. He was the first to study the products of the selenium dehydrogenation of cholesterol and isolated a hydrocarbon (CigHig), which became known as "Diels hydrocarbon." This substance proved to possess the basic steroidal ring structure its subsequent synthesis by Diels in 1935 (almost 30 years after he started this work) led to the rapid elucidation of the structures of a vast array of steroidal sex hormones, saponins, cardiac glycosides, bile pigments, and adrenal cortical hormones, such as cortisone. 

Physiological adaptations in marasmus involve the breakdown of body tissues for energy which is stimulated by catabolic hormones, such as those from the adrenal cortex, and the reduction or cessation of protein synthesis and growth in many tissues. The specific effects of the adrenal cortical hormones are the breakdown of proteins to amino acids, and conversion of amino acids to glucose for use by the brain and nervous system. 

The elimination of the side chain, which here leads to the synthesis of a hormone, is on the other hand a catabolic reaction for the adrenal cortical hormone 17-hydroxy-l 1-deoxycorticosterone. As we have mentioned, the hormones are inactivated by reduction in ring A. The urinary excretion product androsterone is formed by the oxidative loss of the side chain at C-17 and reduction of ring A. 

In the biosynthetic steps from progesterone to the adrenal cortical hormones are the very important 21-, lljS-, and 18-hydroxylations. The major pathway of synthesis is illustrated in Fig. 18. The properties of the enzyme, 17a-hydroxylase, which catalyzes the initial step in the formation of cortisol, have been described in a previous section, IV.B, of this manuscript. 21-Hydroxylation of progesterone or 17a-hydroxy-progesterone precedes 1 lj8-hydroxylation resulting in the eventual formation of the glucocorticoids, corticosterone, and cortisol respectively. The further conversion of corticosterone by 18-hydroxylation and sub-... 

Amri H, Drieu K, Papadopoulos V. (1997). Ex vivo regulation of adrenal cortical cell steroid and protein synthesis, in response to adrenocorticotropic hormone stimulation, by the Ginkgo biloba extract EGb 761 and isolated ginkgolide B. Endocrinology. 138(12) 5415-26. 

The final step in cortisol synthesis requires transport of 11-deoxycortisol back to the inner membrane of the mitochondria, where P450cn (11-P-hydroxylase) receives electrons from electron transport protein intermediates (adrenodoxin, which when oxidized is reduced by adrenodoxin reductase). The enzyme then transfers these reducing equivalents by way of oxygen to 11-deoxycortisol for hydroxylation at Cl 1 to form cortisol. The rate of biosynthesis of cortisol and other adrenal steroids is dependent on stimulation of the adrenal cortical cells by adrenocorticotropic hormone (ACTH). 

Even the most ardent supporters of the belief that ascorbic acid is concerned in the synthesis of cortical hormones would probably hesitate today to suggest that this is the most important function of ascorbic acid in the body, still less its only function there are too many obvious reasons for thinking otherwise. The first is that human patients whose adrenals have been destroyed suffer from Addison s disease but do not develop scurvy. They continue to show normal levels of ascorbic acid in the blood (Jenovese el al., 1940), and there is no evidence that their collagen is affected. Though there were some initial reports (e.g., Wilkinson and Ashford, 1936) that patients with Addison s disease suffered from ascorbic acid deficiency, this idea has faded from the recent literature. Secondly, the amount of ascorbic acid in the adrenal cortices is less than 1 per cent of the total amount in the human body (Section III, 2) it would be against what we know of the economy of the body to think that all the rest of this active metabolite was simply hanging around in the other tissues, waiting for the adrenals to find a use for it. 

Cells of the adrenal cortex utilize cholesterol for the synthesis of a number of steroid hormones, including cortisol. Although these cells can themselves synthesize cholesterol, it is often also necessary for additional cholesterol to be obtained from plasma lipoproteins. A high concentration of LDL receptors enables cortical cells to take up LDL, which contains cholesterol, rapidly. 

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