Download Steroid Hormones

Steroid Hormones
Estrogen & Progesterone
The Female Body
Estrogen
– Development of
secondary sex
characteristics
– Growth of uterus
during puberty
– Initial growth of
endometrium
during menstrual
cycle
Progesterone
– Development of
breasts during
puberty
– Growth of
endometrium
during menstrual
cycle
– Inhibition of uterine
contractions during
pregnancy
The Ovarian Cycle
Follicular Stage
-GnRH induces release
of LH & FSH
-Follicular growth &
secretion of estradiol
Ovulation Stage
-Follicle bursts releasing
mature ovum
-Broken follicle develops
into corpus luteum
The Ovarian Cycle
Luteal Stage
-Corpus luteum secretes estrogen and
progesterone
-Estrogen & progesterone decrease GnRH, LH &
FSH levels inhibiting further ovulation
-No fertilization in 25 days leads to the
endometrial deterioration
Fertilization
-Zygote produces an LH-like hormone so the
corpus luteum can secrete estrogen &
progestrone causing the endometrium to stay in
place
Endogenous Estrogens
Biosynthesis of Estrogen
and Progesterone
Aromatase Inhibitors
Aromatase
- Cytochrome P-450 complex that catalyzes
the conversion of androstenedione to
estrone and testtosterone to estradiol
Steroidal Aromatase Inhibitors
- Irreversible
- Act as natural substrate of aromatose
Aromatase Inhibitors
Non-Steroidal
Aromatase Inhibitors
- Reversible
- Enough estrogen
displaces these
- Anastrozole (Shown)
Estrogen Receptor Types
ER-α
- Found in uterus, vagina, breasts, and
kidneys
- 595 amino acid residues
ER-β
- Found in ovaries, lungs, and bladder
- 485 amino acid residues
Estrogen Receptor Domains
A/B Domain
- Contains AF-1
C Domain
- DNA binding domain
- Contains 2 Zinc fingers
D Domain
- Translocates complex into
nucleus
E Domain
- Hormone / Ligand binding region
- Contains AF-2
- Where ER-α and ER-β differ
Estrogen Receptor Action
Agonists
- Cause helix 12 to sit
snuggly over domain D
- AF-2 is capable of
achieving transcription
Antagonists
- Rearrange formation
of helix 12
- AF-2 is incapable of
transcription
Estrogen Antagonists
- Help treat and prevent estrogen dependent breast cancer
- Characteristics of a good antagonist
- Substitution at 7-α with long alkyl
chain
- Substitution at 11-β with long, non
polar substituents
Fulvestrant
- Characteristics of a bad antagonist
- Substitution at 7-α with bulky chains, alcohol, carboxylic
acid, aryl, or ester groups
-Substitution at 11-β with polar groups
Selective Estrogen Receptor Modulators
Tamoxifen
- Antagonist to breast tissue
- Agonist to endometrium,
liver, and bone tissue
Raloxifen
- Antagonist to breast and
endometrial tissue
- Agonist to bone tissue
Progestins
Natural Progesterone
Synthetic Progestins
- Deletion of methyl group at
carbon-13
- Addition of double bond
between carbon 6 and 7
- Added substituent at
carbon-12
Oral Contraceptive Agents
- Believed to suppress the production of LH and
FSH so that ovulation does not occur
- Monophasic combinations such as Yasmin,
contain the same amount of drug in each tablet (
3 mg of drosperinone and 30 mg of ethinyl
estradiol )
Oral Contraceptive Agents
- Biphasic and triphasic combinations
mimic the variation of estrogen and
progesterone levels naturally created
by the body
- Ortho-Tri-Cyclen
- Tablet of 0.18 mg of norgestimate and 35
mg of ethinyl estradiol for 7 days
- Tablet of 0.215 mg of norgestrimate and
35 mg of ethinyl estradiol for 7 days
- Tablet of 0.25 mg of norgestrimate and 35
mg of ethinyl estradiol for 7 days
Abortifacient : Mifepristone
- Progesterone receptor antagonist of the uterus
- Promotes shedding of endometrium, softening of
the cervix, and uterine contractions leading to
spontaneous abortion
- Often used in conjunction with misoprostol
prostoglandin
Conclusion
- The natural steroid hormones estrogen
and progesterone are produced in
large quantities by our bodies.
- Synthesized versions are important to
the medical community because they
provide hope for breast cancer
patients, allow for contraception, and
can be used for abortion.