Adrenocortical Hormones

Selective Androgen Receptor Modulators (SARMS

Draw:

1. Phenanthrene

2. Perhydrophenanthrene

3. Cylopentanoprehydrophenanthrene

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2 methyl groups, one at c-13 and the other at c-10

there is also a 2 carbon side chain at c-17

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methyl at c- 13

NO side chain at C-17

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Have two methyl groups, one at C-13 and the other at C-10 ·

Have an 8-carbon side-chain attached at C-17 

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Have two methyl groups, one at C-13 and the other at C-10 ·

Do NOT have a side chain at the 17-position 

substituents (and hydrogens) which are below the plane of the rings are designated as α,above the ring plane as β. Alpha is also used to denote substituents which are on the opposite side of the CH3 groups in cholesterol while beta are on the same side of the molecule as CH3 groups of cholesterol. 

The stereochemistry of the hydrogen at C-5 (if present) must always be included in the name of the steroid (e.g.. 5α-estrane) since the geometry at this ring fusion determines the shape of the steroid. 

Double bonds are specified with the number of the position from which the bond originates followed by -ene. If the double bond can be drawn in only one direction, or if it goes to the next highest numbered position, only the starting position needs to be specified. 5α-Cholest-6-ene (assumes a double bond between the 6- and 7-positions) If however, a double bond is formed to any position other than the next highest number, or if it can be drawn in two different directions, the end of the double bond also needs to be specified. 

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Cortisone 17α,21-Dihydroxy-4-pregnene-3,11,20-trione 

Name the intermediates from cholesterol to Aldosterone.

hint: there are 3 and from the middle one there is 3 more. 

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Explain.

1. Something affects the happothalamus it produces CRH and commicates with anterior pituitary to produce ACTH which influences that Adrenal Cortex to produce Cortisol.

2. Cortisol inhibits Hypothalamus and Anterior Pituitary and Inhibit the IMMUNE SYSTEM from producing TNF, IL1, 2, 6 (all stimulants of hypothalamus and pituitary)

3. Cortisol is highest in the morning. Trauma via nociceptive pathways, drive for cicadain rhythm and emotion via limbic system can all stimulate Hypothalamus. 

Dexamethasone suppression test: measures the response of the adrenal glands to ACTH. Cortisol levels should decrease in response to the administration of dexamethasone. The test is given at low and high doses of Dexamethasone and the levels of cortisol are measured to obtain the results. A normal result is a decrease in cortisol levels and ACTH upon administration of low-dose dexamethasone. Results indicative of Cushing's disease involve no change in cortisol on low-dose dexamethasone, but inhibition of cortisol on high-dose dexamethasone. If the cortisol levels are unchanged by low and high-dose dexamethasone then a cortisol secreting adrenocortical tumor is suspected or an ectopic ACTH syndrome. 

Metabolic Effects

Stimulate gluconeogenesis: In the liver, induce the transcription of a number of enzymes involved in gluconeogenesis and amino acid metabolism, including phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, and fructose-2, 6-bisphosphatase 
Increase serum glucose 
Catabolize muscle, skin and bone (osteoporosis), pediatric growth inhibition 
Stimulate both lipolysis and lipogenesis: net effect is fat deposition in particular anatomical areas (moon face , buffalo hump) 
•Immunosuppressive Effects

Inhibits lymphocytes, can delay organ transplant rejection. 

Caution when used with active infections 
•Anti-inflammatory Effects

Can prevent or suppress inflammation in response to radiant, mechanical, chemical, infectious, and immunological stimuli 
Inhibit the transcription factors (e.g. nuclear factor kappa-beta NF-κB) necessary in the production by multiple cells (especially lymphocytes) of critical components (e.g. cytokines) in generating the inflammatory response,. There is decreased release of vasoactive and chemo-attractive factors, diminished secretion of lipolytic and proteolytic enzymes, decreased extravasation of leukocytes to areas of injury. 
Macrophages and monocytes which need PGs and leukotrienes are inhibited by glucocorticoid induction of a protein (lipocortin) that inhibits phospholipase A2. 
Decrease COX-2 , IL-2 and IL-3, and the inflammatory cytokine (PAF) platelet activating factor 
Inhibits basophile IgE mediated release of histamine. 

•Other Effects Stimulate gastric acid secretion and can result in ulcers

                  Potential Adverse Effects of Glucocorticoid Steroid Therapy

1) Gastrointestinal effects due to

(a) decreased mucosal protection

(b) increased secretion of HCl

2) Edema due to

(a) sodium retention and potassium loss; little mineralocorticoid activity

(b) hypokalemia

3) Osteoporesis due to

(a) inhibition of osteoblastic formation

(b) inhibition of Ca2+ reabsorption

4) Gluconeogenesis

(a) insulin antagonism

(b) elevated serum triglycerides

5) Growth inhibition

(a) decreased dosage in children

6) CNS effects (a) euphoria b) increased mental alertness (c) irritability (d) psychotic behavior (e) manic-depressive (extreme cases)

7) Myopathy

8) Ocular effects

9) Miscellaneous a) “Moon face” b) acne c) hirsutism d) purpura (purple skin and mucous membrane patches)

Crushing syndrome- hypercortisolism, condition that arrises when the body is exposed to high leves of cortisol for an extended period. (Moon face and buffalo hump is a tell-tell sign) Other symptoms include: growth retardation, thick neck, fat trunk/abdomen, thin extremities, diabetes melitius, muscle wasting and weakness. 

Addision Disease- condition of Primary Adrenocortical Deficiency. "general languor and debility, feebleness of the heart's action, irritability of the stomach, and a peculiar change of the color of the skin" 

1. All Glucocorticoids have substition at what position?

2. What is an epimer and name two widely use mineralocoticoids

1. 7th position. 

2. Deamethasone and Betamethasone

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name some different substituents and their effects.. Some of the SARs.. 

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1. Hydroxyl group at c21 on ring d is on all corticosteroids and most synthetic analogs. absolute requirement for mineralocorticoid activity but not glucocorticoid.