Steroids estrogens synthetic estrogens estrogen antagonists progestins synthetic progestins
Download
1 / 37

CHEM-5398 April 1, 2010 - PowerPoint PPT Presentation


  • 148 Views
  • Uploaded on

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

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' CHEM-5398 April 1, 2010' - carly-harvey


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Steroids estrogens synthetic estrogens estrogen antagonists progestins synthetic progestins

Steroids: Estrogens, Synthetic Estrogens, Estrogen Antagonists, Progestins, Synthetic Progestins

CHEM-5398

April 1, 2010


Outline
Outline Antagonists,

  • Background: Steroids overview, etc

  • History

  • Estrogen

  • Synthetic Estrogens

  • Estrogen Antagonists/SERMs

  • Progesterone

  • Synthetic Progestins

  • Hormone Replacement Therapy (HRT)

  • Future Research…


Steroids basics
Steroids basics Antagonists,

  • Steroid hormones are all derived from cholesterol

  • Cholesterol contains cyclopentanophenanthrene ring

  • Estrogen and progestins are just two of the many steroids found in the human body

Cholesterol


Steroid basics
Steroid basics Antagonists,

  • Mechanism:

    - 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


  • Mechanism (ctd) Antagonists,

    - Hormone binding activates receptor protein and now both can bind specific regions of DNA called HRE

    (Hormone Response Elements)


Video Antagonists,


Ovarian and Antagonists, Menstrual

cycles

and the

contraceptives

link


History
History Antagonists,

  • 1926: Loewe and Lange discovered that a female sex hormone varied throughout menstrual cycle.

  • 1928: Zondek reported excretion of estrogen during pregnancy.

  • In 1929 Adolf Butenandt and Edward Adelbert Doisy independently isolated and determined the structure of estrogen.

  • The first orally effective estrogen, Emmenin, was derived from the late-pregnancy urine of Canadian women, and was introduced in 1930


Estrogens
Estrogens Antagonists,

  • Function as the primary female sex hormones

  • Present in both men and women

  • Promote development of female secondary sex characteristics

  • Stimulate endometrial and uterine growth

  • Reduce bone resorption, increase bone formation


Estrogens1
Estrogens Antagonists,

  • Fun fact: Estrus = fertile, gen = to generate in Latin

  • Three major types of natural estrogens

Estrone (E1)

Estradiol (E2)

Most common!

Estriol (E3)


Estrogens2
Estrogens Antagonists,

  • From menarche to menopause the primary estrogen is 17β-estradiol

  • Estradiol is produced from testosterone


Estrogen receptors
Estrogen Receptors Antagonists,

  • Estrogens act as signaling molecules by interacting with specific target cells.

    • Include tissues of the breast, uterus, brain, heart, liver, and bone.

  • These target cells have estrogen receptors.

    • There are two estrogen receptors that are normally found in the cell’s nucleus: ER α and ER β.

  • The receptor undergoes dimerization in order for it to have increased affinity for DNA.



Menopause
Menopause sites, called estrogen response elements (EREs).

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


Synthetic estrogens
Synthetic Estrogens sites, called estrogen response elements (EREs).

  • Can by synthesized from plants or biological organisms like horses

  • Examples include Synthroid or Quinestrol

Synthroid

Quinestrol


Estrogen antagonists serms
Estrogen Antagonists/SERMs sites, called estrogen response elements (EREs).

Estrogen antagonists are proteins that block the actions of estrogen by binding to estrogen receptors

As a result, estrogen can not bind

Example: Evista/Raloxifene


Serms
SERMs sites, called estrogen response elements (EREs).

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!

Tamoxifen


Uses of serms
Uses of SERMs.. sites, called estrogen response elements (EREs).

Used before or after menopause

Can help in slowing metastasis of cancer

Can treat osteoporosis

Advantage: specificity

Yet to find a SERM that has no negative side effect (delte this: both mentioned cause colon cancer)


Progesterone progestins
Progesterone/Progestins sites, called estrogen response elements (EREs).

Progesterone (pregn-4-ene-3,20-dione)


History1
History sites, called estrogen response elements (EREs).

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


Progesterone
Progesterone sites, called estrogen response elements (EREs).

Involved in female menstrual cycle, supports pregnancy, and embryogenesis in the womb

Synthesis:

Progesterone

Cholesterol

Pregnenolone


Progestins
Progestins sites, called estrogen response elements (EREs).

Most frequent uses: Contraception and endometrial hyperplasia

Enovid/Norethynodrel: contraceptive


Progestin antagonists
Progestin antagonists sites, called estrogen response elements (EREs).

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)

Mifepristone


Hormone replacement therapy hrt
Hormone Replacement Therapy (HRT) sites, called estrogen response elements (EREs).

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


Modes of hrt
Modes of HRT sites, called estrogen response elements (EREs).

Combination:

- Pills and patch

Estrogen:

- Pills, patch, cream

Progestins

- Pills, vaginal gels,

IUDs


Combination hrts
Combination HRTs sites, called estrogen response elements (EREs).

Pills:

Prempro

Patches:

CombiPatch


Patches vs pills
Patches vs. Pills sites, called estrogen response elements (EREs).

Different routes of administration = different side effects

Pills 2x likely to cause blood clots than patches


Estrogen hrts
Estrogen HRTs sites, called estrogen response elements (EREs).

Pills: Estrace

Patches: Vivelle-dot

Cream*: Dienestrol

Dangers of Estrogen Video

Dienestrol


Progestin hrts
Progestin HRTs sites, called estrogen response elements (EREs).

Pills:Prometrium

IUDs:

Mirena (levonorgestrel)

Lasts up to 5 years


Negative effects of hrt
Negative effects of HRT sites, called estrogen response elements (EREs).


Mayo clinic research on hrt risks
Mayo Clinic Research on HRT risks sites, called estrogen response elements (EREs).

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


Future research
Future research… sites, called estrogen response elements (EREs).

How testosterone and estrogen work together to control male dimorphic behaviors in rats (UCSF)

Alzheimer’s Disease and estrogen after menopause


Assigned reading
Assigned Reading: sites, called estrogen response elements (EREs).

Goodman and Gilman’s Pharmacological Basis of Therapeutics pp. 1541and 1548-1568. Large Print Only


  • Homework Questions: sites, called estrogen response elements (EREs).

  • What is a SERM? What are SERMs used for? Draw the structure of tamoxifen.

  • What is Combipatch and how is it used? Draw the structures of the two ingredients and list the general classes of molecules to which each of these two ingredients belongs.


Sources
Sources sites, called estrogen response elements (EREs).

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. 


ad