1. Number of Nuclear Positions and Steroid Classification
Nomenclature of Steroids
Number of Nuclear Positions and Steroid Classification
C-27 skeleton
… Cholestanes
C-24 skeleton
… Cholanes
C-21 skeleton
… Pregnanes
C-19 skeleton
… Androstanes
C-18 skeleton
… Estranes

2. Usage of ‘Nor’ terminology
Nomenclature of Steroids
Usage of ‘Nor’ terminology
C-27 skeleton
… Cholestanes
18-Nor C-27 skeleton
… 18-nor cholestane
C-19 skeleton
… Androstanes
19-Nor C-19 skeleton
… 19-nor androstane

3. Female Sex Hormones (Estrogens and Progestins)
Control:
Follicle –Stimulating Hormone (FSH) stimulate the production of Estrogens.
Luteinizing Hormone (LH) stimulate the production of Progestins.

4. Estrogens Natural Estrogens: Excreted by human ovary
It has 1/3 the effect of estradiol.
It is the metabolite by oxidation
of estradiol.

5. Physiological Effects
Uses
Birth control pills.
Failure of ovarian development.
Menstrual disturbances.
Suppress lactation after birth.
Postmenopausal osteoporosis.
Prostate cancer.
Side Effects
Nausea, vomiting and diarrhea.
Sodium and water retention.
Inhibition of ovulation in large doses.

6. SAR Aromatic ring with C-3-OH is essential for activity.
Steroidal structures is not essential for activity.
Alkylation of the aromatic ring decrease the activity.
The 17b-hydroxyl with constant distance from 3-OH is essential for activity.
The group between the two hydroxyl must be hydrophobic.
Unsaturation of ring B decreases the activity.
17a- and 16 position when modified enhance the activity.

7. Steroidal Estrogenic Drugs
Estradiol:
Most active natural estrogen.
Very short duration of action due to first pass metabolism.
Mainly used for local effect on the uterus.
Ethinyl estradiol (17-α-ethynylestradiol).
more potent than estradiol orally.
Estra-1,3,5(10)triene-3,17-diol

8. Nonsteroidal Estrogens
1. Diethylstilbesterol:
The trans form is the active one.
Advantages:
As active as Estradiol.
Longer duration of action.
Orally active
Cheap.
Disadvantages:
Increase the risk of uterine cancer.
Uses:
Treatment of prostate cancer.
Trans -diethylstilbene-4,4'-diol.

9. Nonsteroidal Estrogens
2.Chlortrianisene:
Tris(p-anisyl)chloroethene.
Active orally

10. Xenoestrogens (Enviromental Estrogens)
Estrogenic compounds with weak activity present in food and drinks.
Isoflavones and coumestrol (Coumestan derivatives) present in family Leguminosae are examples of xenoestrogens.

11. Estrogen Antagonists Uses: Treatment of estrogen dependent cancers.
Triphenylethylene antagonists:
They are related to stilbene in structure.
Antagonist bind strongly to the receptors.
Aromatase inhibitors:
Steroidal or nonsteroidal.
Block conversion of androgens to estrogens.
Uses: Treatment of estrogen dependent cancers.

12. Antiestrogens Triphenylethylene antagonists 1.Clomiphene (clomid)
R = Cl
It acts as ovulation stimulant by
increasing gonadotrophin hormone (GRH).
50 mg dose for 5 days starting from 5th day of menstruation
If ovulation dose not occur, the dose is increased to 100 mg.
2. Tamoxifen (Nolvadex):
R = CH3CH2-.
Used in treament of early & advanced breast cancer in postmenopausal women.

13. Progestins
Progesterone is the major natural progestin.
Secretion: By the ovary mainly the corpus luteum during the second half of the menstrual cycle.
Physiological Effects:
Development of the endometrium.
Development of the mammary gland during pregnancy.
Milk secretion starts when its level decrease with birth.
Thermogenic action.
Preg-4-ene-3,20-dione.

14. SAR Steroidal nucleus essential for activity.
Have some androgenic activity.
Removal of the 19 CH3 increase activity.
Unsaturation of ring B or C increase the activity.
Removal of the keto function remove androgenic activity.

15. Progestrogenic Drugs 1. Lynestrenol:
Semisynthetic progestin with pure progestrogenic activity.

16. Uses: Side Effects: Contraceptive pills. Uterine bleeding.
Prevention of abortion.
Amenorrhea, dysmenorrhea, endometriosis.
Suppression of lactation.
Endometrial, renal and breast carcinoma.
Enhance respiration (for Hypoventilation).
Side Effects:
Nausea, vomiting, irregular bleeding, edema, weight gain, breakthrough bleeding, breast discomfort.

17. Progestrogenic Drugs 2. Medroxyprogestrone (provera)
17-α-acetoxy-6-α-methylpreg-4-ene-3,20-dione.
Uses: Oral contercetptive.

18. Progestin Antagonists
1. Mifepristone:
Compete with the progestin receptors.
Uses:
Contraceptive.
Abortifacient.
11-β-(p-dimethylaminophenyl)-
17-β-hydroxy-17-α-(1-propynyl)-
estra-4,9-diene-3-one.

19. Male Sex Hormones (Androgens)
Control:
Luteinizing Hormone (LH) or Interstatial Cell-Stimulating Hormones (ICSH) stimulate the production of Androgens.

20. Androgenic Steroids – Physiological Activities
Primarily two activities – Androgenic and Anabolic
Androgenic Activity
Growth and development of male sex organs
Important for male sex drive and performance
Development of secondary sexual characteristics
Important role in spermatogenesis
Anabolic Activity
Development of muscle mass
Reverse catabolic or tissue-depleting processes
Side Effects:
Sodium and water retention leads to edema.
Masculinization of women.
Hepatic dysfunction.

21. Natural Androgens:

22. Structure Activity Relationships in Androgens
Generalizations
Steroid skeleton is necessary
An electronegative (may not be oxygen) at 3 position is required
A/B ring fusion should be either trans or presence of a double bond at 4 position
Alkyl group (CH3) at 17a-position is necessary for anabolic activity
Alkyl group at 17a- confers oral activity

23. Androgens & anabolic agents
1.Testosterone:
17-β-hydroxy-androst-4-ene-3-one
In male:
FSH stimulates sperm production
LH stimulates secretion of testosterone.
Medical Uses:
Treatment of hypogonadism {decreased functional activity of the gonads, thus resulting in lower amounts of testosterone}.
Androgens possess anabolic activity.
Treament of breast cancer in menopausal women.
Dysmenorrhea but of no advantage over Progestins & estrogens.

24. Adverse effects of testosterone
Virilization (female)
Feminizing side effects (male)
Precocious puberty (i.e early puberty) & stunted growth (reduced growth rate).
Cholestatic jaundice
Enlargement of prostate
Atherosclerosis
Hepatic carcinoma
Oedema

25. 2. 17 a-methyltestosterone:
Androgenic Drugs
2. 17 a-methyltestosterone:
(17-β-hydroxy-17-α-methyl-androst-4-ene-3-one)
Orally active.
Prolonged action.
Androgenic and anabolic effects.
* 3. Fluoxymestrone:
10 times more potent than testosterone.

26. Anabolic Steroids
Class of steroid hormones related to the male hormone – testosterone
Increase protein synthesis within cells which results in growth of muscle
Also have androgenic properties which include the development and maintenance of males characteristics
Have both medical and sport performance uses

27. Anabolic Steroids Anabolic Effects
Two different, but overlapping effects
Anabolic – promote cell growth. Increased protein synthesis, appetite, bone remodeling and growth, and production of red blood cells
Increase the size of muscle fibers (hypertrophy) leading to increase in muscle mass and strength
Decrease the amount of fat in muscle

28. Anabolic Steroids Androgenic Effects
Androgenic (virilizing) - development and maintenance of male characteristics:
Increased growth of pubic, beard, chest and limb hair
Enlargement of vocal cords
Suppression of natural sex hormones

29. Anabolic Steroids Adverse Effects
Most side effects are dose dependent
Elevated blood pressure (most common)
Increase LDL cholesterol and decrease HDL
Increase risk of CV disease and coronary artery disease, arrhythmias, and heart attacks (chronic use)

30. Anabolic Steroids Adverse Effects
Accelerate the rate of premature baldness (male and female)
Acne – stimulates the sebaceous glands
Liver damage (cancer) – increased demand on liver as oral steroids are changed (increase bioavailability and stability)

31. Anabolic Steroids Adverse Effects
Tendon rupture has been linked to AS
Stiffer and less elastic tendon
Probably tendon does not adapt as fast.
Gynecomastia – development of breast tissue in males
Conversion of testosterone to estrogen by an aromatase enzyme
Temporary infertility (decreased production of sperm)
Testicular atrophy (caused by decrease levels in natural testosterone)

32. Anabolic Steroids Behavioral Effects
Controversial
Mood swings
Aggression (roid rage)
Mania
Depression
Withdrawal
Dependence

33. Anabolic Steroids Medical Uses
Bone marrow stimulation – aplastic anemia
Growth stimulation – use GH now
Appetite stimulate – AIDS, cancer
Induction of male puberty – extreme delay
Reversible male contraceptive - future
Hormone replacement therapy (men)
Gender dysmorphia - psyciatric

34. Oral Anabolic Steroids
17-alpha methyl testosterone (Android)
17-alpha ethyl testosterone (Maxibolin)
1-methyl testosterone (Primobolan)
Androstenediol (“Andro” food supplements)
Androstenedione
Dihydroepiandrosterone (DHEA)

35. Injectable Anabolic Steroids
19-nortesterone ester derivitives (Durabolin)
Testosterone ester derivatives (Oreton)
Testosterone cypionate derivatives (Virilon)
Boldenone
Stanozolol (Winstrol) oral form as well

36. Synthetic Anabolic Steroids:
1. Norethandrolone
Orally active.
Anabolic effects.
C-10 CH3 group removed eliminate androgenic effect.
2. Stanozolol
Orally active.
Anabolic effects.
Stanozolol

37. Anabolic agents 3. Oxymetholone: 17-β-hydroxy-17-α-methyl-2-(hydroxy-
methylene)androstan-3-one.
4. Oxandrolone:
17-β-hydroxy-17-α-methyloxandrostan-3-one
5. Nandrolone: (nortestosterone)
Used as ester (decanoate or
phenylpropionate)

38. Structure Activity Relationships in Androgens
Anabolic Androgenic
Testosterone
(injectable)
Testosterone
esters (injectable)
R = COCH2CH propionate
= CO(CH2)5CH enanthate
= COCH2CH2(C5H9) cypionate

39. Structure Activity Relationships in Androgens
Anabolic Androgenic
17a-methyl
Testosterone
(oral)
Fluoxymesterone
(oral)

40. Structure Activity Relationships in Androgens
Anabolic Androgenic
Nandrolone
(injectable)
Oxymetholone
(oral)

41. Structure Activity Relationships in Androgens
Anabolic Androgenic
Stanozolol
(oral)
Dromostanolone
(oral)

42. Androgen Antagonists Androgen Receptor Antagonists: 1. Danazol
* Weak androgenic, anabolic, progestational & glucocorticoid action
2. Cyproterone acetate:
Has antiandrogenic and progestrogenic activity.
Used for treatment of acne, hirsutism, prostate hypertrophy, prostate cancer and precocious puberty.
3. Flutamide:
Non steroidal antiandrogen.
Used for treatment of hirsutism and prostate cancer
4. 5a-Reductase inhibitors:
They prevent conversion of testosterone into dihydrotestosterone.
Used for treatment of Benign Prostatic Hyperplasia (BPH).

43. Finesteride (5  reductase inhibitors)
Androgens Antagonists
Danazol
(endometriosis)
Finesteride (5  reductase inhibitors)
(baldness)
Cyproterone acetate
(prostate cancer)
Flutamide
(prostate cancer)

44. Male Contraceptives Gossypol: Side Effects:
Is a phenolic compound present in cotton seed oil.
Decrease number of sperms and impairs their motility.
Its effect is reversible.
Side Effects:
Hypokalemia, weakness, diarrhea and edema.

45. 1,25-Dihydroxy Vitamin D3
1,25-dihydroxy Vitamin D3 is also derived from cholesterol and is lipid soluble
Not really a “vitamin” as it can be synthesized de novo
Acts as a true hormone

46. Photobiosynthesis of vitamin D3 and its metabolismOH
25(OH) D3
Liver
25-OHase
OHase = hydroxylase
Diet
UV from
sunlight
Skin
Specific receptors in intestine, bone, kidney
Ca:
Intestinal absorption
Renal reabsorption
PO4:
Intestinal absorption Renal reabsorption
Kidney
1-OHase OH HO
1,25(OH)2 D3
(active hormone form) HO 7
Provitamin D3
(7-dehydrocholesterol:
Intermediate in cholesterol synthesis)
Photobiosynthesis of vitamin D3 and its metabolism

47. The hormonal interactions controlling bone mineral homeostasis
Figure The hormonal interactions controlling bone mineral homeostasis. 1,25(OH)2D is produced by the kidney under the control of PTH, which stimulates its production, and FGF23, which inhibits its production. 1,25(OH)2D in turn inhibits the production of PTH by the parathyroid glands. 1,25(OH)2D is the principal regulator of intestinal calcium and phosphate absorption. Both PTH and 1,25(OH)2D regulate bone formation and resorption, each capable of stimulating both processes. This is accomplished by their stimulation of preosteoblast proliferation and differentiation into osteoblasts, the bone forming cell. PTH and 1,25(OH)2D stimulate the expression of RANKL by the osteoblast, which, with MCSF, stimulates the differentiation and subsequent activation of osteoclasts, the bone resorbing cell. FGF23, fibroblast growth factor; MCSF, macrophage colony-stimulating factor; OPG, osteoprotegerin; RANK, receptor for activation of nuclear factor-kB.

48. Actions of Vitamin D on Gut, Bone, and Kidney
Vitamin D 
Intestine
Increased calcium and phosphate absorption by 1,25 (OH)2D  
Kidney
Calcium and phosphate excretion may be decreased by 25(OH)D and 1,25(OH)2D1  
Bone
Increased calcium and phosphate resorption by 1,25(OH)2D; bone formation may be increased by 1,25(OH)2D and 24,25(OH)2D  
Net effect on serum levels
Serum calcium and phosphate both increased