Steroid Hormones Estrogen Progesterone The Female Body Estrogen

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 -Gn. RH 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 Gn. RH, 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.