Steroids: Estrogens, Synthetic Estrogens, Estrogen Antagonists, Progestins , Synthetic Progestins. CHEM-5398 April 1, 2010. Outline. Background: Steroids overview, etc History Estrogen Synthetic Estrogens Estrogen Antagonists/SERMs Progesterone Synthetic Progestins
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April 1, 2010
- Modulate gene expression inside cell
- They are not water-soluble so travel in blood attached to protein carriers
- When they reach the cell, they dissociate from protein carrier and enter membrane
- Some bind to a receptor in the cytoplasm and move in to the nucleus
- Hormone binding activates receptor protein and now both can bind specific regions of DNA called HRE
(Hormone Response Elements)
Transition period in a woman's life when her ovaries stop producing eggs, her body produces less estrogen andprogesterone, and menstruation becomes less frequent
Symptoms are mood swings, hot flashes and vaginal dryness
Estrogen antagonists are proteins that block the actions of estrogen by binding to estrogen receptors
As a result, estrogen can not bind
Selective Estrogen Receptor Modulators
Because Estrogen receptors differ slightly in different organs, SERMs can target receptors of a certain organ
So a SERM that blocks estrogen’s effects in breast cells won’t impact estrogen binding in the uterus!
Used before or after menopause
Can help in slowing metastasis of cancer
Can treat osteoporosis
Yet to find a SERM that has no negative side effect (delte this: both mentioned cause colon cancer)
1935: Progesterone is discovered and named
1938: first orally active progestin is synthesized in Germany
1950s: More viable oral progestin synthesized in Mexico City by Miramontes; approved in US
Involved in female menstrual cycle, supports pregnancy, and embryogenesis in the womb
Most frequent uses: Contraception and endometrial hyperplasia
When these bind receptors, they produce a delay in endometrial maturation and postpone the appearance of the implantation window
Therefore, used to terminate pregnancies
PRMs – Progesterone receptor modulators (contraceptives)
Estrogen + progestins or either!
Medical treatment for menopausal or post-menopausal women
Progestins keep weight off and stop cell proliferation
Benefits of estrogen:
Reduction in loss of bone mass (osteoporosis)
Decreased risk of cardiovascular disease
Positive effect on cognitive function
- Pills and patch
- Pills, patch, cream
- Pills, vaginal gels,
Different routes of administration = different side effects
Pills 2x likely to cause blood clots than patches
Dangers of Estrogen Video
Lasts up to 5 years
In the largest clinical trial to date, the combination estrogen-progestin (Prempro) increased the risk of certain serious conditions.
According to the study, over one year, 10,000 women taking estrogen plus progestin might experience:
- Seven more cases of heart disease than women taking a placebo
- Eight more cases of breast cancer than women taking a placebo
- Eight more cases of stroke than women taking a placebo
- Eighteen more cases of blood clots than women taking a placebo
How testosterone and estrogen work together to control male dimorphic behaviors in rats (UCSF)
Alzheimer’s Disease and estrogen after menopause
Goodman and Gilman’s Pharmacological Basis of Therapeutics pp. 1541and 1548-1568. Large Print Only
The Pharmacological Basis of Therapeutics by Goodman and Gilman
“Progesterone vs Progestin” by Dr. Steven Hotze
“Perspective: Female Steroid Hormone Action” by Dr. Orla Conneely
General, Sascha; Terebesi, Ildiko; Bracht, Stefan; Funke, Adrian. Progestin -containing drug delivery system. PCT Int. Appl. (2010), 77pp.
Daniels, Rolf. Estrogen drug delivery systems. Pharmazie in Unserer Zeit (2004), 33(5), 392-397.
Simmons, Horst Ernest. The Side Effects of Estrogen Drug Therapy: Contraception and Postmenopause. (1979), 92 pp.