1. Estrogen & Progesterone
Steroid Hormones
Estrogen & Progesterone

2. The Female Body Progesterone Estrogen
Development of breasts during puberty
Growth of endometrium during menstrual cycle
Inhibition of uterine contractions during pregnancy
Estrogen
Development of secondary sex characteristics
Growth of uterus during puberty
Initial growth of endometrium during menstrual cycle

3. 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

4. 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

5. Endogenous Estrogens

6. Biosynthesis of Estrogen and Progesterone

7. 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

8. Aromatase Inhibitors Non-Steroidal Aromatase Inhibitors - Reversible
- Enough estrogen displaces these
- Anastrozole (Shown)

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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 )

16. 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 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

17. 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

18. 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.