Steroid hormone synthesis

LDL is the major carrier of cholesterol to the periphery and supplies the cholesterol essential for the integrity of nerve tissue, steroid hormone synthesis, and cell membranes. The association between elevated plasma cholesterol carried in LDL and the risk of coronary heart disease has been well established. LDL is also sometimes called the bad cholesterol. 

J.F. Strauss, 3rd, F. Martinez, and M. Kiriakidou. Placental steroid hormone synthesis Unique features and unanswered questions. Biol Reprod. 54 303-311 (1996). 

Testes (Leydiy cells) Ovary (Follicles and Steroid hormone synthesis... 

D. Cholesterol is not only an important contributor to the structural properties of cell membranes, but it is also the precursor for steroid hormone synthesis and a major component of the lipoproteins. 

Steroid hormones synthesis alteration Fregmmcy. could be prolonged... 

Ketoconazole Blocks fungal P450 enzymes and interferes with ergosterol synthesis Poorly selective interferes with mammalian P450 function Broad spectrum but toxicity restricts use to topical therapy Oral, topical Toxicity and interactions Interferes with steroid hormone synthesis and phase I drug metabolism... 

Reactions described in this chapter that are catalyzed by mixed-function oxidases are those involved in fatty acyl-CoA desaturation (Fig. 21-13), leukotri-ene synthesis (Fig. 21-16), plasmalogen synthesis (Fig. 21-30), conversion of squalene to cholesterol (Fig. 21-37), and steroid hormone synthesis (Fig. 21-47). 

Pituitary hormone stimulation of steroid hormone synthesis and secretion. 

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... 

Niacin and pantothenic acid synergistic wilh ACTH in steroid hormone synthesis Vitamin D antagonized directly by AC-TH via cortisol action... 

The principal physiological functions of tins vitamin include growth, production of visual purple, maintenance of skin and epithelial cells, resistance to infection, gluconeogenesis. mucopolysaccharide synthesis, bone development, maintenance of myelin and membranes, maintenance of color and peripheral vision, maintenance of adrenal cortex and steroid hormone synthesis, Specific vitamin A deficiency diseases include xerophthalmia, nyctalopia, hemeralopia, keratomalacia, and hyperkeratosis. 

Mitochondria play a central role in a variety of biological processes, including ATP synthesis, steroid hormone synthesis, the urea cycle, lipid and amino acid metabolism, and cellular Ca2+ homeostasis. Ca2+ is an essential regulator of vital processes, such as secretion, motility, metabolic control, synaptic plasticity, proliferation, gene expression and apoptosis. Therefore, the location, amplitude,... 

One of the goals of many workers in this field is the development of drugs that specifically can interrupt steps in steroid hormone synthesis or action. A few of the affinity reagents to be discussed have been tested for their physiological effects on hormone-dependent processes in mammalian systems. The results of these in vivo applications will be indicated for those systems where they are available. 

Ketoconazole (an antifungal agent, see p. 340) strongly inhibits all gonadal and adrenal steroid hormone synthesis. It is used in the treatment of patients with Cushing s syndrome. 

Figure 33-2. Hypothalamic-pituitary-adrenal axis. Corticotropin-releasing hormone (CRH) acts to increase pituitary ACTH secretion, which enhances steroid hormone synthesis by the adrenal, including production of cortisol (hydrocortisone), which controls CRH/ACTH secretion via negative feedback.

Figure 33-5. Summary of the pathway and enzymes catalyzing steroid hormone synthesis from precursor cholesterol. Reproduced with permission from White and Speiser (2000). Copyright 2000,The Endocrine Society...

New MI, White PC Genetic disorders of steroid hormone synthesis and metabolism. Baillieres Clin Endocrinol Metab 9 525-554,1995. 

It should be noted that in addition to the GABA(A)-R benzodiazepine-binding sites or central benzodiazepine Rs (CBZ-Rs) there are peripheral benzodiazepine Rs (PBZ-Rs) associated with the outer membrane of mitochondria in glial cells and cells of peripheral tissue and which are involved in cholesterol transport and hence in regulation of steroid hormone synthesis. The GABA(B)-Rs are metabotropic and coupled via heterotrimeric G proteins to Ca2+ and K+ channels (Chapter 5). The psychotropic GABA breakdown product y-hydroxybutyrate (GHB) also acts via heterodimeric G protein-linked receptors (see Chapter 5). 

The mineralocorticoid aldosterone is also produced by the adrenal cortex and promotes retention of H20 and Na+ and loss of K+ by the kidney. Cortisol is also an agonist of the aldosterone receptor but the level of cortisol is kept low by type 2 11 (Thydroxysteroid dehydrogenase, which converts cortisol to the inactive cortisone (11-dehydrocortisol). Accordingly inhibition of this enzyme by 18(i>-glycyrrhetinic acid (from liquorice) elevates cortisol with consequent effects of H20 and Na+ retention, oedema and hypertension. Further potential sites of interference by plant substances with steroid hormone metabolism include enzymes involved in steroid hormone synthesis such as the cytochrome P450-linked 11 -hydroxylase that catalyses the last step of corticosterone synthesis. 

The similarities between ecdysone synthesis in the insect prothoracic gland and the ovary are obvious and in each case synthesis is initiated in response to a hormone originating in the brain. Both bear a striking resemblance to the mammalian system where steroid hormone synthesis in the various endocrine tissues is initiated in response to the release of appropriate hormones from the anterior pituitary. 

FIGURE 10,27 Role of cytochromes in steroid hormone synthesis and fatly acid desaturation. 

Cadmium decreases testosterone production by preventing the synthesis of cholesterol, a precursor of all steroid hormones. Other chemicals that interfere with steroid hormone synthesis include aminoglute-thimide, cyanoketone, and ketoconazole. Copper chelating compounds, such as dithiocarbamates, metam sodium, and carbon disulfide, suppress the conversion of dopamine to norepinephrine and subsequently to epinephrine. 

W. L. Miller Molecular biology of steroid hormone synthesis. Endocrine Reviews 9, 295(1988). 

---