Cholesterol and hormones

Madan, D.K. and Cadwallader, D.E. (1973). Solubility of cholesterol and hormone drugs inilvflfe irm. 

Cadwallader DE, Madan DK. Effect of macromolecules on aqueous solubility of cholesterol and hormone drugs. J Pharm Sci 1981 70 442-446. 

Define steroids and describe their chemical structure. Be able to discuss the importance of the steroids known as cholesterol and hormones. 

Testosterone promotes muscle growth deepening of the voice the growth of body hair and other male secondary sex characteristics Testosterone is formed from cholesterol and IS the biosynthetic precursor of estradiol the principal female sex hormone or estrogen Estradiol is a key substance m the regulation of the menstrual cycle and the reproductive process It is the hormone most responsible for the development of female secondary sex characteristics... 

The breast cancer resistance protein (BCRP) belongs to the G-branch of the ABC-transporter family (ABCG2). In contrast to most other ABC-proteins, BCRP consists of only one transmembrane domain (TDM) with one nucleotide binding fold (NBF) at its C-terminus. Because of this structural characteristic BCRP as well as other ABC-transporters with only one TMD are termed half transporters. To achieve functional activity these transporters have to form hetero- or homodimers. BCRP is involved in the multidrug resistance of certain tumors and transports endogenous compounds like cholesterol and steroid hormones. 

Ness GC> Chambers CM Feedback and hormonal regulation of hepatic d-hydroxy-d-methylglutaryl coen me A reductase the concept of cholesterol buffering capacity. Proc Soc Exp Biol Med 2000 224 8. 

BALMIR F, STAACK R, JEFFREY E, JIMENEZ M D, WANG L and POTTER S M (1996) An extract of SOy flour influences serum cholesterol and thyroid hormones in hamsters. J Nutr. 126 (12) 3046-53. 

Vitamins and Other Nutrients in Food Matrices see also Section 6.3. Food matrices are available with values assigned for vitamins, carotenoids, fatty acids, cholesterol, natural toxins, veterinary drugs, and hormone residues. The NIST food matrix SRMs for vitamins include coconut oil (SRM 1563), infant formula (SRM 1846), and baby food composite (SRM 2383) (particularly for carotenoids). Fatty acids and cholesterol are the primary analytes of interest in meat homogenate (SRM 1546) and diet... 

Steroid hormones are produced by the adrenal cortex, testes, ovaries, and placenta. Synthesized from cholesterol, these hormones are lipid soluble therefore, they cross cell membranes readily and bind to receptors found intracellularly. However, because their lipid solubility renders them insoluble in blood, these hormones are transported in the blood bound to proteins. Furthermore, steroid hormones are not typically preformed and stored for future use within the endocrine gland. Because they are lipid soluble, they could diffuse out of the cells and physiological regulation of their release would not be possible. Finally, steroid hormones are absorbed easily by the gastrointestinal tract and therefore may be administered orally. 

Steroids, compounds with a cyclopenta[a]phenanthrene skeleton (15), include a wide range of natural products such as sterols (e.g., cholesterol), sex hormones, adrenocorticoid hormones, cardiac glycosides and vitamin D [31]. Sterols are steroids having a hydroxyl group at position 3 of the basic skeleton. Steroids can be found both in plants and in animals. 

During treatment of hyperthyroidism, Lp(a), as well as LDL cholesterol and apolipoprotein B, increases, indicating an effect of thyroid hormone on receptor activity and on protein synthesis. The opposite effect is observed in treatment of hypothyroidism (B27, E9, K16). 

Cholesterol is a fat-hke substance (a sterol) that is present in our blood and all the cells. It is synthesized within the body or derived from our diet. Cholesterol is an important constituent of the cell membrane and hormones. 

Lipids such as cholesterol and testosterone act as hormones to regulate body functions. (Not all hormones are lipids. Some hormones are proteins. Other hormones are neither lipids nor proteins.)... 

Cytochrome P450 pathways in human brain cholesterol, steroid hormones, vitamin D, and bile... 

The clinical problems that arise in the menopause are hot flushes, sweating, depression, decreased libido, increased risk of cardiovascular disease and osteoporosis. The latter results in increased incidence of hip, radial and vertebral fractures. Oestrogen is one factor controlling synthesis of active vitamin D and osteoporosis is in part due to a deficiency of vitamin D. Not surprisingly, to reduce these problems, administration of oestrogen is recommended (known as hormone replacement therapy or HRT). HRT reduces some of the risk factors for coronary artery disease since it reduces blood pressure and decreases the blood level of LDL-cholesterol and increases that of HDL-cholesterol. However, there is considerable debate about whether HRT increases the risk of breast or endometrial cancer. 

Examples are shown in Fig. 23.9. Stereochemistry is indicated by dotted lines (a-bonds, behind the plane) and solid lines (P-bonds, in front of the plane) of any substituents on the rings. The sex hormones are the molecules mainly responsible for differentiating the sexes. The difference between testosterone and progesterone is a hydroxy versus an acetyl group. The natural sex hormones are used to treat prostate cancer, to alleviate menopausal distress, and to correct menstrual disorders. Other common natural steroids are estradiol, cholesterol, and cortisone. Infamous... 

Receptors can mediate the action of endogenous signalling compounds and may therefore be viewed as regulatory proteins. Such receptors are the physiological targets for neurotransmitters and hormones. Other types of receptors include enzyme proteins, transport proteins and structural proteins. For example, statins inhibit an enzyme catalysing the synthesis of cholesterol and loop diuretics inhibit an enzyme that facilitates the re-uptake of salt in primary urine. 

Sterols. Molecules related to cholesterol and some hormones. 

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