Steroids

Steroids

1. Steroids by nabeela jabeen Mphil pharmacognosy

2. Introduction A steroid is an organic compound with four rings arranged in a specific molecular configuration.  Steriodial nucleus

3. Classification Development and control of reproductive tract in man e.g. estradiol, progesterone, testosterone Molting of insects e.g. ecdysone Induction of sexual reproduction in aquatic fungi e.g antheridiol Therapeutic classification e.g digitalis ( digitoxin ) Vitamin D precursor ( ergosterol ) Oral contraceptive e.g semisynthetic estrogen and progestin Antiinflammatory drugs e.g corticosteroids Anabolic agent e.g androgen

4. Nomenclature of steroids A steroid is any compound that contain “ Cyclopentanohydrophenanthrene ” nucleus Steroids are numbered and rings are letters as indicated in structural formula of steroids When the ring are denoted as projections onto the plane of the paper an atom or group attached to a ring is termed as alpha if it lies below the plane of the paper If it lies above the plane of the paper is termed as beta configuration

5. I n formula, bonds in alpha confriguration are designated by broken lines while in beta confriguration , substitution of atom or groups are represented by hard lines In most steroids, rings B and C and rings C and D are fused trans Rings B and C either cis or trans

6. Bile acids Bile acids are  steroid   acids  found predominantly in the  bile  of mammals and other vertebrates.  Different molecular forms of bile acids can be synthesized in the  liver  by different species .  Bile acids are conjugated with  taurine  or  glycine  in the liver, forming primary bile acids. The sodium and potassium salts of bile acids are called bile salts

7. Primary bile acids are those synthesized by the liver.  Secondary bile acids result from bacterial actions in the  colon . In humans,  taurocholic acid  and  glycocholic acid  (derivatives of  cholic acid ) and  taurochenodeoxycholic acid  and  glycochenodeoxycholic acid  (derivatives of  chenodeoxycholic acid ) are the major bile salts in bile and are roughly equal in concentration .

8. The conjugated salts of their 7-alpha-dehydroxylated derivatives,  deoxycholic acid  and  lithocholic acid , are also found, with derivatives of cholic , chenodeoxycholic and deoxycholic acids accounting for over 90% of human biliary bile acids

9. Bile acids compose about 80% of the organic compounds in bile (others are  phospholipids  and  cholesterol ).  An increased secretion of bile acids produces an increase in bile flow. The main function of bile acids is to allow  digestion of dietary fats and oils  by acting as a  surfactant  that  emulsifies  them into  micelles ,  allowing them to be  colloidally  suspended in the  chyme  before  further processing . 

10. Structures Cholic acid

11. Glycocholic acid

12. Taurocholic acid

13. Chenodeoxycholic acid Chenodeoxycholic acid

14. Phytosterol has been completed in glycosides chapter in which includes Digitalis Squill

15. Steroids hormones A steroid hormone is a  steroid that acts as a hormone. Steroid hormones can be grouped into two classes:  Corticosteroids  (typically made in the adrenal cortex, hence  cortico - ) Sex steroids  (typically made in the gonads or placenta). Within those two classes are five types according to the receptors to which they bind: glucocorticoids, mineralocorticoids (corticosteroids), androgens, estrogens, and  progestogens  (sex steroids).

16. Adrenal cortex Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main of corticosteroids ,  glucocorticoids  and  mineralocorticoids ,

17. Both are involved in a wide range of physiologic processes, including  stress response,  immune response, and regulation of inflammation,  carbohydrate  metabolism,  protein  catabolism, blood  electrolyte levels, behavior

18. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors, target cells, and effects. In technical terms, "corticosteroid" refers to both glucocorticoids and mineralocorticoids (as both are mimics of hormones produced by the adrenal cortex), but is often used as a synonym for "glucocorticoid."

19. Glucocorticoids Glucocorticoids are chiefly produced in the  zona fasciculata  of the adrenal cortex Mineralocorticoids  mineralocorticoids are synthesized in the  zona glomerulosa . Difference between Glucocorticoids AND Mineralocorticoids  

20. Effects Immune As discussed in more detail below, glucocorticoids function through interaction with the glucocorticoid receptor: up-regulate the expression of anti-inflammatory proteins. down-regulate the expression of proinflammatory proteins. Glucocorticoids are also shown to play a role in the development and homeostasis of T lymphocytes.

21. Metabolic The name "glucocorticoid" derives from early observations that these  hormones  were involved in  glucose metabolism . In the fasted state,  cortisol  stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood.

22. Metabolic effects: Stimulation of  gluconeogenesis , in particular, in the  liver : This pathway results in the synthesis of glucose from non hexose  substrates, such as  amino acids  and  glycerol  from triglyceride breakdown, and is particularly important in  carnivores  and certain  herbivores . Enhancing the expression of  enzymes  involved in gluconeogenesis is probably the best-known metabolic function of glucocorticoids

23. Mobilization of  amino acids  from  extrahepatic  tissues: These serve as substrates for gluconeogenesis. Inhibition of glucose uptake in muscle and  adipose  tissue: A mechanism to conserve glucose Stimulation of  fat breakdown  in adipose tissue: The fatty acids released by  lipolysis  are used for production of energy in tissues like muscle, and the released  glycerol  provide another substrate for gluconeogenesis.

24. Cortisone

25. Mineralocorticoids Mineralocorticoids are a class of corticosteroids, which are a class of steroid hormones. Mineralocorticoids are corticosteroids that influence salt and water balances (electrolyte balance and fluid balance). The primary mineralocorticoid is aldosterone, notable for an aldehyde group at the 18 position.

26. Effects The name mineralocorticoid derives from early observations that these hormones were involved in the retention of sodium, a mineral . The primary endogenous mineralocorticoid is aldosterone, A lthough a number of other endogenous hormones (including  progesterone and   deoxycorticosterone ) have mineralocorticoid function.

27. Aldosterone acts on the kidneys to provide active reabsorption of sodium and an associated passive reabsorption of water, As well as the active secretion of potassium in the principal cells of the cortical collecting tubule and active secretion of protons via proton  ATPases  in the lumenal membrane of the intercalated cells of the collecting tubule. This in turn results in an increase of blood pressure and blood volume .

28. Aldosterone is produced in the zona glomerulosa of the cortex of the adrenal gland and its secretion is mediated principally by angiotensin II but also by adrenocorticotrophic hormone (ACTH) and local potassium levels.

29. Sex steroids Sex steroids, also known as gonadal steroids, are  steroid hormones   with  vertebrate androgen or estrogen  receptor. Their effects are mediated by slow genomic mechanisms through nuclear receptors  as well as by fast nongenomic mechanisms through membrane-associated receptors and signaling cascades . The term  sex hormone  is nearly always synonymous with  sex steroid . The non-steroid hormones luteinizing hormone, follicle-stimulating hormone and gonadotropin-releasing hormone are usually not regarded as sex hormones, although they play major sex-related roles.

30. Production Natural sex steroids are made by the gonads (ovaries or testes ), by  adrenal glands, or by conversion from other sex steroids in other tissue such as liver or fat.

31. Types In many contexts, the two main classes of sex steroids are androgens and estrogens, of which the most important human derivatives are testosterone and estradiol, respectively. Other contexts will include  progestogens  as a third class of sex steroids, distinct from androgens and estrogens. 

32. Progesterone is the most important and only naturally occurring human progestogen . In general, androgens are considered "male sex hormones", since they have masculinizing effects, while estrogens and progestogens are considered "female sex hormones“ although all types are present in each sex, albeit at different levels.

33. Sex steroids include: Androgens Androstenedione Dehydroepiandrosterone Dihydrotestosterone Testosterone Estrogens Estradiol Estriol Estrone Progestogens Progesterone

34. Androgen An androgen (from Greek  andro  meaning male human being) is any natural or synthetic compound, usually a  steroid hormone , that stimulates or controls the development and maintenance of male characteristics in  vertebrates  by binding to  androgen receptors . This includes the activity of the primary  male sex organs  and development of male  secondary sex characteristics . Androgens were first discovered in 1936.

35. Androgens increase in both boys and girls during puberty . Androgens are also the original  anabolic steroids  and the precursor of all  estrogens . The primary and most well-known androgen is  testosterone . Dihydrotestosterone  (DHT) and  androstenedione  are less known generally, but are of equal importance in male development. DHT in the embryo life causes differentiation of penis, scrotum and prostate.

36.  Later in life DHT contributes to balding, prostate growth and  sebaceous gland  activity. Although androgens are described as male  sex hormones , both males and females have them to varying degrees, as is also true of estrogens. They are one of three types of sex hormones, the others being  estrogens  like  estradiol  and  progestogens  like  progesterone .

37. Androgen

38. Estrogen Estrogen ( American English ) or  oestrogen  ( British English ) is the primary  female   sex hormone  as well as a  medication . It is responsible for the development and regulation of the female  reproductive system  and  secondary sex characteristics .  Estrogen  may also refer to any substance, natural or synthetic, that mimics the effects of the natural  hormone . The   estrane   steroid   estradiol  is the most potent and prevalent  endogenous  estrogen, although several  metabolites  of estradiol also have estrogenic hormonal activity

39. Estrogens are used as  medications  as part of some  oral contraceptives , in  hormone replacement therapy  for  postmenopausal ,  hypogonadal , and  transgender women , and in the treatment of certain  hormone-sensitive cancers  like  prostate cancer  and  breast cancer Estrogens are synthesized in all vertebrates  as well as some insects.

40. The three major naturally occurring forms of estrogen in women are  estrone  (E1),  estradiol  (E2), and  estriol  (E3). Another type of estrogen called  estetrol  (E4) is produced only during pregnancy. Quantitatively , estrogens circulate at lower levels than androgens in both men and women .   While estrogen levels are significantly lower in males compared to females, estrogens nevertheless also have important physiological roles in males .

41. ESTROGEN

42. Progestogens , also sometimes spelled  progestagens  or  gestagens , are a class of  steroid hormones  that bind to and activate the  progesterone receptor  (PR ). Progesterone  is the major and most important progestogen in the body, while  progestins  are  synthetic progestogens

43. Major examples of progestins include the  17α- hydroxyprogesterone  derivative  medroxyprogesterone acetate  and the  19-nortestosterone  derivative  norethisterone  ( norethindrone ). The progestogens are named for their function in maintaining  pregnancy (i.e.,  progestational ), although they are also present at other phases of the  estrous  and  menstrual cycles .

44. PROGESTERON

45. Withanolide ( phytosterol ) Withanolides  are a group of at least 300 naturally occurring  steroids  built on an  ergostane  skeleton .  They occur as  secondary metabolites  primarily in  genera  of the  Nightshade family , for example in the  tomatillo . Structurally, withanolides consist of a  steroid backbone  bound to a  lactone  or one of its  derivatives ; they are produced via  oxidation  of steroids . It remains unknown to what end withanolides are produced; they may act as deterrent for feeding insect larva and other herbivores .

46. uses Anticancer Radiosensitizing Antibacterial Immunomodulatory Antioxidant Hepatoprotective Antistress Anti-inflammatory Withanolide

47. E cdysone a steroid hormone that controls moulting in insects and other arthropods . Ecdysone  is a  steroidal   prohormone  of the major insect  molting  hormone  20-hydroxyecdysone , which is secreted from the  prothoracic glands . Insect molting hormones ( ecdysone and its homologues) are generally called  ecdysteroids . Ecdysteroids act as moulting hormones of  arthropods  but also occur in other related  phyla  where they can play different roles.

48. In  Drosophila melanogaster , an increase in ecdysone concentration induces the expression of genes coding for proteins that the larva requires, and it causes chromosome puffs (sites of high expression) to form in polytene chromosomes. Ecdysteroids also appear in many plants mostly as a protection agent (toxins or antifeedants ) against herbivorous insects. These   phytoecdysteroids  have been reputed to have medicinal value and are part of herbal  adaptogenic  remedies like  Cordyceps , yet an ecdysteroid precursor in plants has been shown to have cytotoxic properties.