Steroid Hormones Estrogen & Progesterone. The Female Body Estrogen –Development of secondary sex...
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Transcript of Steroid Hormones Estrogen & Progesterone. The Female Body Estrogen –Development of secondary sex...
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
- 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
Fulvestrant
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.