steroid lect 1

8/8/2019 Steroid Lect 1

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STEROIDS

Lecture 1



Steroids

Steroids constitute a group of structurally related

compounds that are widely distributed in plant & animal

kingdom

Broad spectrum of important compounds which exhibitremarkable pharmacodynamic properties namely, adrenal

cortical hormones, sex hormones, cardiac glycosides,

saponins, alkaloids, etc

Partly or completely hydrogenated 17H-cyclopenta

phenanthrene nucleus



SEX HORMONES

3 Hormones: 1. Estrogen

2. Progesterone

3. Testosterone (androgens)

Biosynthetic pathway ± Progesterone ± biosynthetic precursor of hydrocortisone & aldosterone

Testosterone - precursor of estrogens

Estrogen, Progesterone: production in large amount in

femalesTestosterone: production in large amount in males

Role: Reproduction, menstrual cycle, characteristic

physical differences,



SEX HORMONES

Synthetic & semisynthetic steroids with biological

activities similar to those of progesterone are progestins

Estrogens, progestins ± chemical contraceptive agents

Testosterone ± 2 activities ± androgenic (promote male physical characteristics), anabolic (muscle building) ± less

selectivity ± all anabolic steroids have androgenic activity



EstrogensActive endogenous estrogens ± estradiol, estrone, estriol

Estradiol ± greatest estrogenic activity, estrone ± less

active, estriol ± least active: activity depends upon affinity

of these estrogens for ER, interconversion between active& inactive metabolites

OH

OH

Estradiol

OH

OH

OH

Estriol

OH

O

Estrone



Estrogens - Biosynthesis

Synthesis: by action of aromatase on androstenedione or

testosterone

Production in large quantity in ovary, placenta

in low quantity in adrenal glands

in trace quantity in testes

Estrogen blood levels are very high during pregnancy

(synthesis in corpus luteum, placenta)

50-350 µg/day of estrogens ± production by ovaries during

menstrual cycle

Placenta ± estriol ± abundant estrogen



OH

H

H H

OH

H

O

H

CYP 450

Side chain cleavage

Cholest erolPregnenolone

H

O

O

H

H

H

Progesterone

H

O

H

O

H

Androstenedione

Aromatase

H

H

O

OH

H

Es trone



Estrogens - Metabolism

Estradiol ± metabolized to estrone (highest conc. in plasma)

Estrone ± converted to estriol (major estrogen in urine) by

hydroxylation at C16 and reduction of C17 ketone ± to give

16 & 17-hydroxyl group

Estradiol ± directly converted to estriol

Other metabolites: 2-hydroxyestrone, 2-methoxyestrone, 4-

hydroxyestrone, 16-hydroxy-17-estradiol

Excretion: 50% in urine (in 24 hrs.), remaining excreted in

bile & reabsorbed ± long time for excretion

Conjugation reactions ± important ± takes place mainly in

liver ± glucuronides, sulphate




OH

OH

OH

O

OH

OH

O

OH

OH

OH

A)

Estr i l Estr

str i ly r s

16 lp - y r xyl s16 lp - y r xyl s

str i ly r s

16 lp - y r xy str Estri l




OH

R

R = O o r O H

H

B )

Es trogen

es trogen 2 /4 -h dro lasees trogen 2 /4 -h dro lase

OH

R

OH

OH

R

O H

2-h dro es trogen4-h dro es trogen

ca techo l O-me th ltransferase( C OMT )

C O M T

OH

R

Me OOH

R

O Me

2-Me tho es trogen 4-Metho es

trogen



Estrogens ± Biological Activities

Development of sex characteristics in women

Growth & development of vagina, uterus, fallopian tubes



Estrogens ± Structural classes

3 Structural classes: 1. Steroidal

2. Diethylstilbestrol

3. Phytoestrogens

Steroidal estrogens: Conjugated & Esterified estrogens

Naturally occurring estrogens found in humans, semisynthetic

derivatives

Conjugated estrogens (equine estrogens) ± are estradiol related

metabolites e.g. Premarin, Equine estrogens (mixture of estrone

sodium sulphate & Equiline sodium sulphate) ± sulphate group to

be removed to release active estrogen, plant source available

Esterified estrogens: combination of estrone sodium sulphate &

Equiline sodium sulphate in different ratio, obtained from plant

sterols



Steroidal estrogens - structures

O

OH

Equilenin

O

ROEquilin: R= HEquilin sodium sulfate:R=



Structures ± DES derivatives

RO

OR

Di thylstilb str l: R= HDi thylstilb str l ipr pi t : R= H

5CO-

Di thylstilb str l ip l it t : R= C15

H31

CO-

OH

OH

Hexestr l



Estrogens ± Structural classes

DES analogues ± dienestrol, benzestrol

OH

OH

Dienestrol

OH OH

Benzestrol



Estrogens ± Structural classesPhytoestrogens:

Natural plant substances

Genistein from soybean & a species of clover, daidzein

from soybean, coumestrol from legumes

Daidzein & coumestrol - isoflavones

O

O

OH O

OH

Coumestr ol

OOH

OH

O

Daidzein



Therapeutic uses

Birth control: inhibition of ovulation

Hormone replacement therapy: for postmenopausal women

Treatment of estrogen deficiency from ovarian failure

Treatment of breast cancer and prostate cancer

Side effects:

Cancer

Not advisable during pregnancy ± high risk of vaginal, uterine,

cervical abnormalities

steroid lect 1

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