1) Adrenocorticoids are steroid hormones produced in the adrenal cortex that include cortisol, cortisone, and aldosterone.
2) They are involved in processes like stress response, immune response, and regulating inflammation, metabolism, electrolyte levels, and behavior.
3) Cortisol is a glucocorticoid that controls carbohydrate, fat, and protein metabolism and has anti-inflammatory effects. Aldosterone is a mineralocorticoid that controls electrolyte and water levels.
4) Advances in studying adrenocorticoids include understanding their effects on rat uterine contractility and brain serotonin metabolism, as well as treating conditions like relative adrenocortical insufficiency
Antioxidant Treatment Induces Hyperactivation of The HPA Axis by Upregulating ACTH Receptor in The Adrenal and Downregulating Glucocorticoid Receptors in The Pituitary
1) Adrenocorticoids are steroid hormones produced in the adrenal cortex that include cortisol, cortisone, and aldosterone.
2) They are involved in processes like stress response, immune response, and regulating inflammation, metabolism, electrolyte levels, and behavior.
3) Cortisol is a glucocorticoid that controls carbohydrate, fat, and protein metabolism and has anti-inflammatory effects. Aldosterone is a mineralocorticoid that controls electrolyte and water levels.
4) Advances in studying adrenocorticoids include understanding their effects on rat uterine contractility and brain serotonin metabolism, as well as treating conditions like relative adrenocortical insufficiency
1) Adrenocorticoids are steroid hormones produced in the adrenal cortex that include cortisol, cortisone, and aldosterone.
2) They are involved in processes like stress response, immune response, and regulating inflammation, metabolism, electrolyte levels, and behavior.
3) Cortisol is a glucocorticoid that controls carbohydrate, fat, and protein metabolism and has anti-inflammatory effects. Aldosterone is a mineralocorticoid that controls electrolyte and water levels.
4) Advances in studying adrenocorticoids include understanding their effects on rat uterine contractility and brain serotonin metabolism, as well as treating conditions like relative adrenocortical insufficiency
1) Adrenocorticoids are steroid hormones produced in the adrenal cortex that include cortisol, cortisone, and aldosterone.
2) They are involved in processes like stress response, immune response, and regulating inflammation, metabolism, electrolyte levels, and behavior.
3) Cortisol is a glucocorticoid that controls carbohydrate, fat, and protein metabolism and has anti-inflammatory effects. Aldosterone is a mineralocorticoid that controls electrolyte and water levels.
4) Advances in studying adrenocorticoids include understanding their effects on rat uterine contractility and brain serotonin metabolism, as well as treating conditions like relative adrenocortical insufficiency
STEROID HORMONE Steroid hormones and related products represents one of the most widely used classes of therapeutic agents. Steroid hormones in mammals are biosynthesized
from Cholesterol, which in turn is made in vivo from
acetyl-coenzyme A(acetyl-CoA) via the mevalonate pathway. Cholesterol synthesis occurs in smooth ER and
enzymatic conversion occur in mitochondria.
Steroid hormones are classified in to two types:- 1.Adrenal cortical hormones 2.Sex hormone
The adrenal cortex secrets steroidal hormone which have
1.Mineralocorticoids-Aldosterone 2.Glucocorticoids- Hydrocortisone 3. Sex Hormones-Androgen and Estrogen. ADRENAL GLAND
ADRENAL CORTEX Outer zone (zona glomerulosa)-secretes mineralocorticoids. Inner zone(Zona fasciculata and reticularis)-secrete
glucocorticoids and adrenal androgens.
ADRENOCORTICOIDS
Adrenocorticoids are a class of chemicals that includes the
steroid hormones that are produced in the adrenal cortex of vertebrates and synthetic analogues of these hormones. Corticosteroids are involved in a wide range of physiological
processes, including stress response, immune response,
and regulation of inflammation , carbohydrate metabolism, protein metabolism, blood electrolyte levels and behaviour. Glucocorticoids: Such as cortisol control carbohydrate, fat and protein metabolism , and anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanism. 1.Hydrocortisone. 2.Cortisone acetate. Mineralocorticoids: Such as aldosterone control electrolyte
and water levels, mainly by promoting sodium retention in the
activity. Eg: Aldosterone,Deoxycortisone. STRUCTURE OF CORTISONE SAR OF ADRENOCORTICOIDS
All cortical steroids contains alpha, beta- unsaturated
ketones in ring A and COCH2OH moiety attached to C-17 that has beta configuration. These requirement are essential for mineralo corticoid activity. Oxygen at C-11is essential for glucocorticoid activity. A
hydroxyl group is superior to C-11keto group.
A 17 alpha group increases glucocorticoid activity. Introduction of a fluoro to 6 alpha position increases both
mineralocorticoid and glucocorticoid activity.
Insertion of double bond at C-1,2 position enhance the glucocorticoid and anti-inflammatory activity.
Introduction of methyl or hydroxyl at C-16 diminishes the
mineralocorticoid SYNTHESIS OF ADRENOCORTICOIDS All steroid hormone have in common the 17- carbon cyclopentanoperhydrophenanthrene nucleus.Additional carbons can be added at positions 10 and 13 or as a side chain attached to C17. Uptake of cholesterol by the adrenal cortex is mediated by the LDL receptor.With long-term stimulation of the adrenal cortex by ACTH,the number of LDL receptor increases.Much of the cholesterol in the adrenal is esterified and stored in cytoplasmic lipid droplets. Upon stimulation of the adrenal by ACTH or Camp, an esterase is activated, and the free cholesterol formed is transported into the mitochondria. In the mitochondria, a cytochrome P450 side chain cleavage enzyme converts cholesterol to pregnenolone. Pregenolone may be converted by dehydrogenase/isomerase to progesterone or else by P450c 17( 17 alpha hydroxylase) to 17 alpha hydroxy pregnenolone. Progesterone can also be converted to 17 alpha hydroxy progesterone. After the synthesis of progesterone and 17- hydroxyprogesterone,P450c21 (21-hydroxylase) can hydroxylate these steroids at the 21 position, resulting in 11- deoxycorticosterone and 11- deoxy cortisol, respectively. The final step in the synthesis of adrenal mineralocorticoids and glucocorticoids is mediated by P450c11(11-beta hydroxylase), which also mediates the final step in the synthesis of aldosterone from deoxycorticosterone. USES Addison Disease: medication given is hydrocortisone to treat it.20- 40mg. Cushing Syndrome: Cushing syndrome is caused by a hyper
secretion of glucocorticoids that results from excessive
release of corticotrophin. Hydrocortisone 300mg IV on the day of surgery. Non endrocrine disease
1.Rheumatic disorder- suppress the disease and minimize
resultant tissue damage. Prednisone 10mg/kg/day. 2.Allergic disease-epinephrine 0.5ml of a 1:1000solution IM. RECENT ADVANCES
The effect of Corticosterone,
cortisone,Desoxycortisone and Hydrocortisone on Rat Uterine contractility at Oestrus.(1966) There is marked increase in blood and urinary levels of adrenocorticoids and their metabolites during pregnancy in women(Loraine and bell 1966).The general purpose of this elevation is presumably related to the need for conservation of energy required during development of the uterus, placenta and foetus. However , the considerable elevation of steroid hormones can be expected to effect uterine contractility. Adrenocorticoids control 5 –hydroxy tryptamine metabolism in rat brain. The influence of surgical adrenalectomy was examined on the biosynthetic capacity for 5-hydroxytryptamine of rat brain.The results demonstrate that adrenalectomy decreased tryptophan hydroxylase activity and its substrate tryptophan in the brain stem. The adrenocortical hormone regulate brain 5-hydroxytryptamine synthesis probably by enhancing both the levels of tryptophan and the activity of rate limiting enzyme tryptophan hydroxylase. It is postulated that emotional instability seen during altered adrenocortical function might partly be associated with abnormal metabolism of central 5-hydroxytryptamine. (published in 2003by R.B.Rastogi and R.L.Singhal) Relative adrenocorticoid insufficiency exists and should be treated. The issue of relative adrenocortical insufficiency(RAI) in septic shock is uncertain. It is defined as an increment of less than 250nmol/L in total serum cortisol level after administration of 250 microgm corticotropin.RAI is associated with increased risk of death, after adjustment for other factors that might independently influence risk. There is strong , but not overwhelming, evidence that administration of low doses of hydrocortisone to patient with septic shock, especially those with RIA improves survival.(Article2006 ) Δ1-Dehydrogenation and C20 Reduction of Cortisone and Hydrocortisone Catalyzed by Rhodococcus Strains(Article 2013) Prednisone and prednisolone are steroids widely used as anti-inflammatory drugs. Development of the pharmaceutical industry is currently aimed at introducing biotechnological processes and replacing multiple-stage chemical syntheses. In this work we evaluated the ability of bacteria belonging to the Rhodococcus genus to bio transform substrates, such as cortisone and hydrocortisone, to obtain prednisone and prednisolone, respectively. These products are of great interest from a pharmaceutical point of view as they have higher anti-inflammatory activity than the starting substrates. After an initial lab-scale screening of 13 Rhodococcus strains, to select the highest producers of prednisone and prednisolone, we reported the 200 ml-batch scale-up to test the process efficiency and productivity of the most promising Rhodococcus strains. R. rubber, R. globerulus and R. coprophilus gave the Δ1-dehydrogenation products of cortisone and hydrocortisone (prednisone and prednisolone) in variable amounts. In these biotransformations, the formation of products with the reduced carbonyl group in position C20 of the lateral chain of the steroid nucleus was also observed (i.e., 20β-hydroxy-prednisone and 20β-hydroxy- prednisolone). The yields, the absence of collateral products, and in some cases the absence of starting products allow us to say that cortisone and hydrocortisone are partly degraded. History of Cortisone and related compounds. Steroidal hormones were isolated from the adrenal cortex in the 1930s and were synthesized a decade later. Several of these structures have highly effective anti- inflammatory activity but also exhibit serious side effects. Chemical analogues have now been discovered with better activity and reduced side effects. Such agents are administered for the treatment of a wide range of inflammatory conditions, including rheumatoid arthritis and asthma. Anti-inflammatory activity can be improved by introducing functional groups or substituents at key positions of the steroid structure. Similarly, substituents placed at key positions can reduce side effects and metabolic susceptibility. Nevertheless, there are still risks associated with the long-term use of steroids, and research is currently looking at novel agents that will act locally at the site of administration and are rapidly metabolised to inactive compounds once they reach the blood supply. Adrenocorticosteroids in peripheral and adrenal venous blood of man. Advances in steroid methodology make possible a direct approach to the problem of the nature of the secretion of the human adrenal cortex. Two experimental studies in which adrenal venous blood was analyzed (1, 2) indicate that 17- hydroxycorticosterone and corticosterone are components of the steroid mixture elaborated by the human adrenal. These two steroids have also been reported to be present in the peripheral blood of man. REFERENCES Organic Chemistry of Natural Products Vol I and Vol II by Gurdeep and Chatwal Organic Chemistry of Natural Products by O.P. Agarwal Steroids and Hormones by V.K.Ahluwalia. Steroids Hormone Receptor by C.R. Clark.
https://journal.chestnet.com.
https//pubmed.ncbi.nlm.nih. https//pubs.acs.org. THANK YOU
Antioxidant Treatment Induces Hyperactivation of The HPA Axis by Upregulating ACTH Receptor in The Adrenal and Downregulating Glucocorticoid Receptors in The Pituitary