Table Of The Major Steroid Hormones
|Pregnenolone: produced directly from cholesterol, the precursor molecule for all C18, C19, and C21 steroids|
|Progesterone: a progestogen, produced directly from pregnenolone and secreted from the corpus luteum, responsible for changes associated with luteal phase of the menstrual cycle, differentiation factor for mammary glands|
|Aldosterone: the principal mineralocorticoid, produced from progesterone in the zona glomerulosa of adrenal cortex, raises blood pressure and fluid volume, increases Na+ uptake via the kidney|
|Testosterone: an androgen, male sex hormone synthesized in the testes, responsible for secondary male sex characteristics, produced from progesterone|
|Estradiol: an estrogen, principal female sex hormone, produced in the ovary, responsible for secondary female sex characteristics|
|Cortisol: dominant glucocorticoid in humans, synthesized from progesterone in the zona fasciculata of the adrenal cortex, involved in stress adaptation, increases gluconeogenesis in liver, elevates blood pressure, increases Na+ uptake by the kidney, numerous effects on the immune system|
Steroid Hormone Enzyme Nomenclature
The various hydroxylases involved in the synthesis of the steroid hormones have a nomenclature that indicates the site of hydroxylation . These hydroxylase enzymes are members of the cytochrome P450 class of enzymes and as such also have a nomenclature indicative of the site of hydroxylation in addition to being identified as P450 class enzymes . The officially preferred nomenclature for the cytochrome P450 class of enzymes is to use the prefix CYP. Thus, 17-hydroxylase is identified as CYP17A1. Another example is the gene encoding the P450ssc enzyme which is identified as CYP11A1. There are currently 57 identified CYP genes in the human genome.
Role Of Gh In Cholesterol And Lipid Metabolism
There exists a negative relationship between obesity and GH. Enormous evidence supports that GH alters lipid metabolism. Clinical studies have shown a significant association between lower serum GH levels and non-alcoholic fatty liver disease . Hypopituitary patients with GH deficiency are more prone to NAFLD than control subjects . GH supplementation has been shown to improve the NAFLD and the metabolic dysfunction . In rodent studies, high-fat diet feeding and obesity suppress pulsatile GH secretion . In turn, chronic GH treatment ameliorates hepatic lipid peroxidation and improves lipid metabolism in high-fat diet-fed rats .
GHR is present in the liver and critical for the hepatic lipid metabolism. Laron dwarfism is a disorder characterized by an insensitivity to GH due to a genetic mutation of GHR. These male patients manifest NAFLD in adults . Liver-specific deletion of GHR in mice leads to increased circulating free fatty acids and fatty liver as a result of increased synthesis and decreased efflux of triglyceride . Binding of GH to GHR activates JAK2-STAT5 signaling pathway and modulates a number of target genes. Among these, altered expression of CD36, PPAR and PGC1/, along with fatty acid synthase, lipoprotein lipase and very-low-density lipoprotein receptor contributes to the hepatic lipid metabolism process . All these findings suggest that hepatic GH signaling is essential for the regulation of intrahepatic lipid and cholesterol metabolism.
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Everyday Connections Bisphenol A And Endocrine Disruption
You may have heard news reports about the effects of a chemical called bisphenol A in various types of food packaging. BPA is used in the manufacturing of hard plastics and epoxy resins. Common food-related items that may contain BPA include the lining of aluminum cans, plastic food-storage containers, drinking cups, as well as baby bottles and sippy cups. Other uses of BPA include medical equipment, dental fillings, and the lining of water pipes.
The Liver And Vitamin Regulation
One of the busiest organs in terms of cholesterol production in our bodies is the liver, which regulates the level of our blood cholesterol. The liver also puts a lot of cholesterol into bile production. Yes, bile is made out of cholesterol. Without bile we would not be able to digest and absorb fats and fat-soluble vitamins. Bile emulsifies fats in other words, it mixes them with water, so that digestive enzymes can get to them. After it completes its mission, most of the bile gets reabsorbed in the digestive system and brought back to the liver for recycling. In fact, 95 percent of our bile is recycled because the building blocks of bile, one of which is cholesterol, are too precious for the body to waste. Nature doesnt do anything without good reason. This example of the careful recycling of cholesterol alone should have given us a good idea about its importance for the body!
Vitamin D has been designed to work as a team with another fat-soluble vitamin: vitamin A. That is why foods rich in one tend to be rich in the other. So, by taking cod liver oil, for example, we can obtain both vitamins at the same time. As we grow older, our ability to produce vitamin D in the skin under sunlight is considerably diminished. Taking foods rich in vitamin D is therefore particularly important for older people. For the rest of us, sensible sunbathing is a wonderful, healthy and enjoyable way of getting a good supply of vitamin D.
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Isopentenyl Pyrophosphate Is A Precursor For A Wide Variety Of Biomolecules
Before this chapter ends, we will revisit isopentenyl pyrophosphate, the activated precursor of cholesterol. The combination of isopentenyl pyrophosphate units to form squalene exemplifies a fundamental mechanism for the assembly of carbon skeletons of biomolecules. remarkable array of compounds is formed from isopentenyl pyrophosphate, the basic five-carbon building block. The fragrances of many plants arise from volatile C10 and C15 compounds, which are called terpenes. For example, myrcene from bay leaves consists of two isoprene units, as does limonene from lemon oil . Zingiberene , from the oil of ginger, is made up of three isoprene units. Some terpenes, such as gera-niol from geraniums and menthol from peppermint oil, are alcohols others, such as citronellal, are aldehydes. We shall see later how specialized sets of 7-TM receptors are responsible for the diverse and delightful odor and taste sensations that these molecules induce.
Analysis Of Ost Activity
The octanoyl tripeptide , N-octanoyl-Asn-Tyr-Thr-amide, which contains the acceptor sequence for N-glycosylation, was received from Dr. Felix Wieland . OTP was prepared and used as a glycosyl acceptor to assay oligosaccharyltransferase activity, as previously described . After incubation with microsomal protein for 1 h at 37 C in the presence and absence of the glucosidase inhibitor, castanospermine , the glycosylated tripeptide was bound to a conA Sepharose column and eluted with buffer containing methyl–d-mannopyranoside and Triton X-100. Activity in the eluate from the conA Sepharose column is expressed as counts per minute per microgram microsomal protein used in the assay.
Analysis of glycotripeptides by thin layer chromatography was performed as previously described . To further define the pattern of glycosylation, the eluted samples were subjected to enzymatic digestion with -mannosidase and Endo H . Aliquots containing approximately equal counts per minute from each sample were incubated with Jack bean -mannosidase or Endo H in the 1× buffer supplied with the -mannosidase, as described in the accompanying literature. The total incubation mixture was 59 l. After incubation at 37 C, overnight , the reaction mixture was spotted on TLC plates, without further processing and the components separated in the solvent system described above.
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Adrenal Microsomal Subfractions From Other Species
To eliminate the possibility that the presence of translocon-associated proteins in adrenal smooth microsomes was confined to the guinea pig, we examined similarly prepared microsomes from adrenals of several species: rat, dog, cattle, rabbit, sheep, and pig. In most, as in the guinea pig adrenal, OST and Sec61 complex subunits as well as the molecular chaperones BiP, GRP94, and calnexin, were found to be in equal or greater concentration in smooth microsomes compared with rough microsomes . The sole exceptions to the equal or greater concentration of these proteins in the smooth microsomes were in the rat adrenal. In the rat adrenal, the OST components as well as BiP and GRP94 were in greater concentration in the rough microsomes. In all of the species examined, however, the SER markers CYP17 and 3HSD were in greater concentration in the smooth microsomes than in rough microsomes. In all cases, the ribosomal protein S3 was localized to the ribosome bearing fractions . This gives increased confidence that the broader distribution of translocon-associated proteins in the ER is a property of most adrenocortical cells and perhaps of steroid-secreting cells in general.
Norethisterone And Norethisterone Acetate
Norethisterone and norethisterone acetate are characterized by very similar pharmacokinetics and pharmacodynamics. Following oral administration NETA is rapidly hydrolyzed to NET. Their bioavailability is 40-80% and depends on molecule size and time of taking the drug . In the blood, NET is bound in 60% to albumins and in 36% to SHBG. The half-life is 9.5 hours and 1.5 hours, respectively. Around 90% of metabolites retain the ethyl group. One of them, 5-dihydro-NET, has a high relative affinity to the AR and is responsible for its weak androgenic activity. A trace amount of NET is aromatized in the liver to ethinyloestradiol, which has no clinical relevance at a dose of 1 mg, however 5 mg of NET is equivalent to the ingestion of 30 µg of EE . Norethisterone demonstrates no glucocorticoid or antimineralcorticoid activity. After taking a single 0.5 mg dose of NETA the maximum concentration of NET in the blood is detected after one hour. For the 1 mg dose, it equals 5-10 ng/ml, and for 2 mg 12 ng/ml. A combination with oestradiol does not alter the pharmacodynamics of NET. Multiple repeated doses ensure a stable concentration of ca. 7.4 ng/ml.
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What Happens If I Have Too Little Dehydroepiandrosterone
Low levels of dehydroepiandrosterone have been linked with shorter lifespan in men but not women. However, the reason for this is not fully understood. Decreased dehydroepiandrosterone levels are associated with increased risk of cardiovascular disease in men with type 2 diabetes mellitus’ data-content=’1282′ > diabetes mellitus and may also cause a shorter lifespan, although further research is needed to confirm this.
In women, low levels of dehydroepiandrosterone are associated with low libido, reduced bone mineral density and osteoporosis. However, supplementation with commercially available dehydroepiandrosterone is not recommended as there is concern about numerous possible side-effects.
The Human Placental Barrier And Placental Model Systems
The hemochorial human placenta results from a deep invasion of embryonic cells during implantation. The mature human placenta is a disk delimited by chorionic and basal plate , which enclose the intervillous space filled with maternal blood. The basal plate contacts the uterine wall. From the chorionic plate, both umbilical cord and the branched chorionic villi originate. The cells of the chorionic villi form the placental barrier, which prevents direct contact of maternal and fetal blood. Biosynthesis, metabolism, and transport of steroids occur in the chorionic villi .
The placenta undergoes significant anatomical changes in the course of pregnancy , which are relevant to maintain appropriate placental function as pregnancy progresses. Hormones in the fetal and maternal circulations have an important role in determining the placental phenotype . As a developing organ that constantly adapts to the maternal environment, not only the structure, but also the transcriptome changes over time . In line with this, expression of various placental genes involved in biosynthesis, transfer or metabolism of steroids changes during pregnancy .
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What Happens If I Have Too Much Dehydroepiandrosterone
Women with polycystic ovary syndrome and hirsutism and children with congenital adrenal hyperplasia’ data-content=’1315′ > congenital adrenal hyperplasia have higher levels of dehydroepiandrosterone/dehydroepiandrosterone sulphate. In addition, levels may be raised in individuals with cancer of the adrenal glands .
High levels of dehydroepiandrosterone have also been linked to reducing the risk of depression, cardiovascular disease and even death in some studies. Some experts have suggested dehydroepiandrosterone supplements might overcome age-related decline but this is not supported by current evidence.
Some athletes and bodybuilders also take dehydroepiandrosterone to increase muscle mass and strength. Serious side-effects from taking manufactured dehydroepiandrosterone have been reported and it is banned by the World Anti-Doping Agency. However, exercise and calorie-restriction have been shown to increase natural dehydroepiandrosterone levels in the body and may lead to longer life.
Since 2000, dehydroepiandrosterone supplementation in combination with gonadotropins has been used in reproductive medicine as a way to treat female infertility.
Steroid Hormone Biosynthesis Reactions
The particular steroid hormone class synthesized by a given cell type depends upon its complement of peptide hormone receptors, its response to peptide hormone stimulation and its genetically expressed complement of enzymes. The following indicates which peptide hormone is responsible for stimulating the synthesis of which steroid hormone:
- Luteinizing Hormone : progesterone and testosterone
- Adrenocorticotropic hormone : cortisol
- Follicle Stimulating Hormone : estradiol
- Angiotensin II/III: aldosterone
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How Is It Broken Down
Once in the blood stream, some cholesterol will be returned to the liver and broken down. Its used to make bile acids which are released into the intestines to help with digestion bile acids break down the fats in food.
A small amount of bile acids will be removed from the body as a waste product in your poo. But most will be absorbed back into the blood, returned to the liver and used again for digestion.
Some treatments for high cholesterol work by stopping bile from being absorbed back into the blood. The liver has to take more cholesterol out of the blood to make more bile, lowering your cholesterol levels.
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Role Of Estrogens In Cholesterol Homeostasis
The influence and mechanism of estrogens on cholesterol metabolism have been investigated for a long time. Studies by Cypriani et al. in 1988 demonstrated that estrogens induced HMG-CoA reductase and subsequent cholesterol synthesis in breast cancer cell line . Later, it was found that HMG-CoA reductase gene promoter contains an estrogen-responsive element-like sequence at position-93 . And, estrogen induction of HMG-CoA reductase gene is dependent on the Red-ERE. The induction activity of estrogens occurs in the breast cancer cells but not in hepatic cells, indicating differential regulation of HMG-CoA reductase by estrogens in a tissue-specific manner . Aromatase is an enzyme responsible for the key step in the biosynthesis of estrogens. Aromatase knockout mice display increased intra-abdominal adipose tissue and lipid droplet accumulation in the liver. Total cholesterol and LDL are also elevated in these transgenes . Supplement of estrogens in both ArKO mice and rats with ovariectomy normalizes LDL and total cholesterol levels, confirming the important role of estrogens in the lipid homeostasis in both males and females . Hormone replacement therapy increases the expression of leucocyte ABCA1 gene, which mediates the efflux of cholesterol to the HDL particles, leading to the subsequent increase in the HDL cholesterol level . Estrogens thus play an important role in the modulation of the total cholesterol level by reducing LDL and concurrently increasing HDL.
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Dietary Sources Of Cholesterol
The Synthesis Of Progesterone And Corticosteroids From Pregnenolone
Progesterone is synthesized from pregnenolone in two steps. The 3-hydroxyl group of pregnenolone is oxidized to a 3-keto group, and the 5 double bond is isomerized to a 4 double bond . Cortisol, the major glucocorticoid, is synthesized from progesterone by hydroxylations at -17, C-21, and C-11 C-17 must be hydroxylated before C-21 is, whereas C-11 can be hydroxylated at any stage. The enzymes catalyzing these hydroxylations are highly specific, as shown by some inherited disorders. The initial step in the synthesis of aldosterone, the major mineralocorticoid, is the hydroxylation of progesterone at C-21. The resulting deoxycorticosterone is hydroxylated at C-11. The oxidation of the C-18 angular methyl group to an aldehyde then yields aldosterone.
Pathways for the Formation of Progesterone, Cortisol, and Aldosterone.
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Dietary Tips To Avoid Cholesterol
The most important thing you can do to reduce your cholesterol level is to maintain a healthy lifestyle. You should try to:
- Increase the amount and variety of fresh fruit, vegetables and wholegrain foods you have each day.
- Choose low or reduced-fat milk, yoghurt and other dairy products or have added calcium soy drinks.
- Choose lean meat .
- Limit fatty meats, including sausages and salami, and choose leaner sandwich meats like turkey breast or cooked lean chicken.
- Have fish at least twice a week.
- Replace butter and dairy blends with polyunsaturated margarines.
- Include foods in your diet that are rich in soluble fibre and healthy fats, such as nuts, legumes and seeds.
- Limit cheese and ice cream to twice a week.
Other storage fats that are transported in blood lipoproteins include triglycerides. When present in high concentrations in the blood, this fat is also a risk for heart attack. Some foods will affect the cholesterol level or the triglyceride level and some will affect both.