teroidal sex harmonesit deals with srtestosterone progesterone

1. Steroidal Sex Hormone
Prepared by
Dr. N.GOPINATHAN
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
FACULTY OF PHARMACY
SRI RAMACHANDRA UNIVERSITY
CHENNAI-116
TAMILNADU

2. Introduction
• Group of steroids
biosynthesised in testes,
ovaries, adrenals and placenta
during pregnancy.
• It is controlled by anterior
lobe of pituitary gland.

3. Androgens – Male sex hormone
• Testes produce mainly one
androgen namely
testosterone.
• It is produced more in males;
however, females produce
this hormone in lower
amount.

4. • It promotes male sex
characteristics-androgenic
activity.
• It promotes muscle building
activity- anabolic activity.
• Androsterone has one seventh
of the activity of testosterone.

5. O
OH
CH3
CH3
OH
OH
CH3
CH3
O
CH3
CH3
OH
Androsterone
Dehydro epiandrosterone Testosterone

6. SAR of Androgens
For a substance to have activity ,it must contain the
androstane skeleton.
Oxygen at C-3 is removed little reduction In activity but
C-17 OH gives sharply reduced androgenic activity

7. • If A/B is cis there is reduce in activity so
trans fusion is needed.
• The position of oxygen atom is
important 2 > 3 > 4.
• The isomer 2 has greater anabolic
activity.
• Esterification of testosterone prolonged
the activity

9. • Halogen substitution produces compounds
with decreased activity except when placed
at C-4 or C-9 position. For example , 9-
fluoro derivatives produces an anabolic
effect 20 times that of 17 alpha-methyl
testosterone.
• Fluoxymesterone [9 fluro substitution] has
anabolic potency 11 times the
unhalogenated derivative.
• Halogen introduction will decrease the
activity except the C-4 and C-9.

10. • The basic nucleus having 5-beta-androstane
which having androgenic activity ,whereas
5-alpha-androstane having no activity.
• There should not be chain constriction or
extension because it leads to finished the
activity.
• Introduction of 3-hydroxy group and 3-keto
group enhance the activity.
• Hydroxy group at C-17 position has no
androgenic or anabolic activity.

11. Introduction of double bond at C-1 position
increases the anabolic activity for example –
methandrostenolone is more active than
methyltestosterone

12. • Replacement of carbon atom at C-2
position by oygen (e.g. oxandrolone)
gives the oral anabolic activity.

13. Removal of CH3 group in testosterone
gives 19-nor testosterone with more
anabolic activity and less androgenic
activity when compared with testosterone.

14. • The introduction of heterocyclic system
into the steroid nucleus in ring A
improve the anabolic activity . For
example ,stanozolol are found to
possess more anabolic activity,
possessing pyrazole .

15. CH3
CH3
CH3
H
H
H
H
CH3
CH3
OH
CH3
CH3
CH3
HH
H
H CH3
CH3
Br
Br
O
O
CH3
CH3
CH3
HH
H
Br
Br
O
O
CH3
O
CH3
CH3
HH
H
O
O
CH3
OCH3
CH3
HH
H
OH
O
CH3
CH3
HH
H
O
O
CH3
CH3
HH
H
O
OH
Chloesterol
Cholesteryl
acetate dibromide
Testosterone
dehydroepiandrosterone

16. Biogenesis of testosterone

17. Estrogens
Estrogen are a group of steroid compounds that
function as the primary female sex hormones
which control the uterine cycle.
Three naturally occuring estrogen are
estradiol,estriol and estrone.
It is synthesised in the grafian follicles, corpus
luteum and placenta from cholesterol.
Oesterodiol is major oestrogen secreted by
ovary.

18. A small quantity of oestradiol is synthesised
in human males.
In male large quantitiy of equilin is produced
in human male
SOURCE:-
Estrogen are produced by developing follicles in the
ovaries , the corpus luteum and the placenta, some
estrogens are also produced in smaller amounts by
other tissues such as liver, adrenal glands and the
breasts . These secondary source of estrogen are
especially important in post menopausal women.

20. Chemical realationship between oestrone
oestriol and oestradiol

25. Estradiol
Estradiol is the primary female sex hormone. It is
important in the regulation of the estrous and menstrual
female reproductive cycles. it also has important effects
in many other tissues including bone. While estrogen
levels in men are lower compared to women, estrogens
have essential functions in men as well.
Properties
•Creamy white
•crystalline powder
•Hygroscopic in nature
• Melting point - 173-179◦C
•Insoluble in water and
soluble in a alcohol

26. Conversion of testosterone to estradiol:-
Estradiol, like other steroids, is derived from cholesterol.
After side chain cleavage and using the delta-5 or the
delta-4 pathway, androstenedione is the key
intermediary. A fraction of the androstenedione is
converted to testosterone, which in turn undergoes
conversion to estradiol by an enzyme called aromatase.

27. Mechanism of action:-
Estradiol acts primarily as an agonist of
the estrogen receptor (ER), a nuclear steroid
hormone receptor.
There are two subtypes of the
ER, ERα and ERβ.
The result of ER activation is a modulation
of gene transcription and expression in ER
expressing cells, which is the predominant
mechanism by which estradiol mediates its
biological effects in the body.

28. DOSE:-
Oral,2mg per day; intramuscular ,1.5 mg 2
or 3 times weekly
USE:-
-- It helps to regulate and subsequent
maintenance of female sex organs, certain
function of the uterus and all the secondary
sex features and the mammary glands.

29. Estriol
It is available for compounding into number of different
formulation for use in Hormonal replacement therapy .
It can be used alone or its combination with estradiol or
with estrone.
--Creamy white ,crystalline powder ,soluble in alcohol.

30. The biosynthetic pathway for the estrogens

31. Does:-
For menopausal symptoms, 250-500 mg per
day.
Therapeutic use:-
Estriol is used to mimic the activity of the
naturally occurring female sex hormone
oestrogen.
It is used in hormone replacement
therapy (HRT).
It is used to relieve symptoms of menopause,
or after surgery to remove the ovaries.

32. SAR of estrogen
•The biologic activity varies with the mode of
administration of estrogens .
• The order of activity of three naturally occurring
steroids when administered subcutaneously is
estradiol ,estrone and estriol.
•The order of activity changes to estriol ,estradiol and
estrone ,when the drugs are administered orally.

33. • Estradiol is not effective orally due to rapid
metabolism in liver but placement of ethinyl
group at C-17 position increase the
resistance to metabolic inactivation and
make the compound orally effective .
• Steroid nucleus is not necessary for
estrogenic activity .Many constituents of
plants like genstein ,coumestrol don’t
contain steroid nucleus but possess
estrogenic activity

34. • Ring A aromatic in nature is essential for
oestrogenic activity.
• OH at 3 is essential, removal lead to
great loss of activity.
• 7 alpha substituent show increased
oestrogenic activity.
• CH2Cl at C-11 with beta configuration
shows more activity.
• 17 beta OH is essential.

35. Progestational agent
• They also called luteum hormones
,mostly secreted by the corpus luteum
portion of the ovary and the metabolised
to various inactive products ,e.g.
pregnanediol.
• The metabolites are essentially excreted
through urine.

36. The natural progestational hormone is progesterone , which is
secreted by the corpus luteum in the second part of the menstrual
cycle.
Small amounts are also secreted by the testis in the male and the
adrenal cortex in both sex and large amounts are secreted by the
placenta.
PROGESTERONE

37. Synthesis:-
Acetylation of diosgenin at 200 degree C gives the
corresponding diosgenyl diacetate which upon oxidation with
chromium-6-oxide removes the side chain at C-17 and the
resulting product on reduction followed by hydrolysis yields
pregnelone .This on being subjected to Oppenauer oxidation
affords the official compound.

38. DOSE:-
10-100 mg intra muscular
Side effects:-
The commonly asociated side-
effects with progestin therapy are
nausea, vomiting,
drowsiness,edema ,irregular
bleeding etc.

39. uses
• Prevent habitual abortion.
• For treatment of functional uterine
bleeding resulting due to the lack
of oestrogens and progesterone
• For treatment of dysmenorrhoea
or painful menstruation
• Pregnancy diagnosis,
• Oral contraceptives,

40. SAR of Progesterones
• Presence of steroid nucleus is
compulsory for pharmacological activity
of progestins.
• Ketone group at C3 is not essential for
the activity of progesterone because
even its removal retains the
progesterone activity CH3
CH3
H
H
H
OH
CH

41. • The L-enantiomer of the compound
resulting from the substitution of ethyl
group of C ring juncture is found to be
active.
• Introduction of halogen or methyl group at
C6 or C7 in alpha configuration increases
hormonal activity.
• Presence of c 19 methyl group is not
essential for activity.
• Addition of Cl or F at C 21 prevents
metabolic hydroxylation and also enhances
oral effectiveness.

42. • Unsaturation of rings A and B enhances
activity.
• Addition of methyl group at C18
increases the activity.
• Acetylation of hydroxyl group at C17 in
ring D increases