Adrenal gland synthesis

Derivation Isolation from extracts of adrenal glands, synthesis from other steroids. 

The original commercial source of E was extraction from bovine adrenal glands (5). This was replaced by a synthetic route for E and NE (Eig. 1) similar to the original pubHshed route of synthesis (6). Eriedel-Crafts acylation of catechol [120-80-9] with chloroacetyl chloride yields chloroacetocatechol [99-40-1]. Displacement of the chlorine by methylamine yields the methylamine derivative, adrenalone [99-45-6] which on catalytic reduction yields (+)-epinephrine [329-65-7]. Substitution of ammonia for methylamine in the sequence yields the amino derivative noradrenalone [499-61-6] which on reduction yields (+)-norepinephrine [138-65-8]. The racemic compounds were resolved with (+)-tartaric acid to give the physiologically active (—)-enantiomers. The commercial synthesis of E and related compounds has been reviewed (27). The synthetic route for L-3,4-dihydroxyphenylalanine [59-92-7] (l-DOPA) has been described (28). 

The adrenal glands are important in the synthesis and regulation of key hormones. They play a crucial role in water and electrolyte homeostatsis, as well as regulation of blood pressure, carbohydrate and fat metabolism, physiologic response to stress, and sexual development and differentiation. This chapter focuses on pharmacologic and nonpharmacologic management of the two most common conditions associated... 

Adrenal hormone production is controlled by the hypothalamus and pituitary gland. Corticotropin-releasing hormone (CRH) is secreted by the hypothalamus and stimulates secretion of adrenocorticotropic hormone (ACTH), also known as corticotropin from the anterior pituitary. ACTH, in turn, stimulates the adrenal cortex to produce cortisol. When sufficient or excessive cortisol levels are reached, a negative feedback is exerted on the secretion of CRH and ACTH, thereby decreasing overall cortisol production. The control of adrenal androgen synthesis also follows a similar negative-feedback mechanism. 

The testes and adrenal glands produce 90% and 10%, respectively, of circulating testosterone. Testosterone enters prostate cells, where predominantly type II 5a-reductase activates testosterone to dihydrotestosterone, which combines with a cytoplasmic receptor. The complex enters the nucleus and induces changes in protein synthesis which promote glandular tissue growth of the prostate. Thus, 5a-reductase inhibitors (e.g., finasteride and dutas-teride) directly interfere with one of the major etiologic factors of BPH. 

Adrenal cortex. The adrenal cortex forms the outer portion of the adrenal gland and accounts for 80 to 90% of the weight of the gland. It is the site of synthesis of many types of steroid hormones such as ... 

Corticosteroids synthesized by the adrenal gland are mineralocorticoids and GC. Min-eralocorticoids regulate fluid and electrolyte balance by affecting ion transport in the kidney. Cortisol, the primary circulating GC in most species (including humans), has many activities, including resistance to stress, regulation of intermediary metabolism, and immunosuppressive and anti-inflammatory effects. GC synthesis and secretion is... 

Corticosteroids are produced by the adrenal glands, and display two main types of biological activity. Glucocorticoids are concerned with the synthesis of carbohydrate from protein and the deposition of glycogen in the liver. They also play an important role in inflammatory processes. Mineralocorticoids are concerned with the control of electrolyte balance, promoting the retention of Na+ and CC, and the excretion of K+. Synthetic and semi-synthetic corticosteroid drugs are widely used in medicine. Glncocorticoids are primarily nsed for their antirhenmatic and anti-inflammatory activities, and mineralocorticoids are nsed to maintain electrolyte balance where there is adrenal insufficiency. 

The adrenal gland and adrenergic neurons continue the synthesis by hydroxylating dopamine into norepinephrine (noradrenaline). Ascorbic acid (vitamin C see p.368) acts as a hydrogen-transferring coenzyme here. 

The arylamino acid decarboxylase inhibitory action of DL-a-fluoromethyldopa (4.77) has also been described. By affecting the enzyme through covalent binding, this compound completely inhibits both catecholamine and serotonin synthesis. Unlike 6-hydroxydopamine, a-fluoromethyldopa does not destroy the neurons, and unlike reserpine it does not deplete chromaffin tissue in the adrenal gland. 

All growing animal tissues need cholesterol for membrane synthesis, and some organs (adrenal gland and gonads, for example) use cholesterol as a precursor for steroid hormone production (discussed below). Cholesterol is also a precursor of vitamin D (see Fig. 10-20a). 

Chapter 22) are released from the adrenal glands. By inducing enzyme synthesis, these hormones increase the amounts of a variety of enzymes within the cells of target organs such as the liver. Glucocorticoids also appear to increase the sensitivity of cell responses to cAMP and hence to hormones such as glucagon.268... 

Angiotensin II has a variety of effects. By constricting blood vessels it raises blood pressure, and by stimulating thirst centers in the brain it increases blood volume. Both angiotensins II and III also act on the adrenal gland to promote the synthesis and release of aldosterone. Most of the effects of angiotension II are mediated by 359-residue seven-helix G-protein linked receptors which activate phospholipase C.p q qr Like other steroid hormones aldosterone acts,via mineralocorticoid receptors, to control transcription of a certain set of proteins. The end effect is to increase the transport of Na+ across the renal tubules and back into the blood. Thus, aldosterone acts to decrease the loss of Na+ from the body. It promotes retention of water and raises... 

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