Estrogen Synthesis The most potent naturally occurring estrogen in humans for both the Estrogen Receptor alpha-and beta-mediated actions is 17beta- estradiol,followed by estrone and estriol Each estrogen contains a phenolic A ring with a hydroxyl group at carbon 3 and a beta-OH or ketone in position 17 of ring D The phenolic A ring is the principal structural feature responsible for selective,high-affinity binding to both receptors Synthesis of estrogen begins from the synthesis of androstenedione from cholesterol Androstenedione crosses the basal membrane into surrounding granulosa cells,where its converted to estrone or estradiol wither immediately or through testosterone The conversion is catalyzed by aromatase
Estrogen Synthesis • The most potent naturally occurring estrogen in humans for both the Estrogen Receptor alpha‐ and beta‐mediated actions is 17beta‐ estradiol, followed by estrone and estriol • Each estrogen contains a phenolic A ring with a hydroxyl group at carbon 3 and a beta‐OH or ketone in position 17 of ring D • The phenolic A ring is the principal structural feature responsible for selective, high‐affinity binding to both receptors • Synthesis of estrogen begins from the synthesis of androstenedione from cholesterol • Androstenedione crosses the basal membrane into surrounding granulosa cells, where its converted to estrone or estradiol wither immediately or through testosterone • The conversion is catalyzed by aromatase
Biosynthetic Pathway This figure shows the major metabolic intermediates in the usual synthesis of estrogen,starting with cholesterol,proceeding to pregnenolone,an androgen,and then estrogen. ea春d(an estro公tm http://www.chemistryexplained.com/Di-Fa/Estrogen.html
Biosynthetic Pathway This figure shows the major metabolic intermediates in the usual synthesis of estrogen, starting with cholesterol, proceeding to pregnenolone, an androgen, and then estrogen. http://www.chemistryexplained.com/Di‐Fa/Estrogen.html
Pharmacokinetics Due to the complex nature of endogenous and exogenous hormone concentration,formation,and metabolism and assay complexity,the pharmacokinetics of estrogen are complicated. Steroids like estrogens and progesterone are small,hydrophobic( molecules that are transported in the blood bound to a serum globulin(球蛋白)， Both naturally occurring estrogens and the synthetic estrogen analogs are well absorbed after their administration though any routes such as gastrointestinal tract,skin,intramuscular or mucous membranes. Oral estrogens has a short half-life in the plasma due to the low bioavailability,since it almost completely undergoes first-pass liver metabolism. Synthetic estrogens,for example,ethinyl estradiol are metabolized more slowly than the naturally occurring estrogens by the liver and peripheral tissues.Therefore,the synthetic estrogen analogs have a prolonged action and high potency as compared to natural estrogens
Pharmacokinetics Due to the complex nature of endogenous and exogenous hormone concentration, formation, and metabolism and assay complexity, the pharmacokinetics of estrogen are complicated. Steroids like estrogens and progesterone are small, hydrophobic(疏水 的 ) molecules that are transported in the blood bound to a serum globulin(球蛋白). Both naturally occurring estrogens and the synthetic estrogen analogs are well absorbed after their administration though any routes such as gastrointestinal tract, skin, intramuscular or mucous membranes. Oral estrogens has a short half‐life in the plasma due to the low bioavailability, since it almost completely undergoes first‐pass liver metabolism. Synthetic estrogens, for example, ethinyl estradiol are metabolized more slowly than the naturally occurring estrogens by the liver and peripheral tissues. Therefore, the synthetic estrogen analogs have a prolonged action and high potency as compared to natural estrogens
Mechanism of action The two estrogen receptor(ER)genes are located on separate How estrogens achieve their effects chromosomes:ESR1 encodes ER- alpha and ESR2 encodes ER-beta Cytoplasm The hormone-receptor complex Ligand enters the nucleus (if it formed in the cytoplasm)and Nucleus binds to specific sequences of DNA, SR called the estrogen(or progesterone) response elements Response elements are located in the promoters of genes. The hormone-receptor complex acts Direct HRE as a transcription factor (often Indirect protein- mRNA recruiting other transcription factors protein interactions to help)which turns on (sometimes Fig.7.Transcriptional action by liganded SRs.TF,transcription factor. off)transcription of those genes. Gene expression in the cell produces the response. Advances in Physiology Education.VOL 31.MARCH 2007
The two estrogen receptor (ER) genes are located on separate chromosomes: ESR1 encodes ER‐ alpha and ESR2 encodes ER‐beta The hormone‐receptor complex enters the nucleus (if it formed in the cytoplasm) and binds to specific sequences of DNA, called the estrogen (or progesterone) response elements Response elements are located in the promoters of genes. The hormone‐receptor complex acts as a transcription factor (often recruiting other transcription factors to help) which turns on (sometimes off) transcription of those genes. Gene expression in the cell produces the response. How estrogens achieve their effects Mechanism of action
Physiological Effects Estrogens and progestins are hormones that produce many physiological actions In women, Developmental effects(estrogens are largely responsible for pubertal changes in girls and secondary sexual characteristics) Neuroendocrine actions involved in:Control of ovulation and the preparation of the reproductive tract for fertilization and implantation Major Actions on:Minerals,Carbohydrates,Proteins,and Lipid Metabolism In men, Bone Spermatogenesis Behavior
Estrogens and progestins are hormones that produce many physiological actions In women, Developmental effects (estrogens are largely responsible for pubertal changes in girls and secondary sexual characteristics) Neuroendocrine actions involved in: Control of ovulation and the preparation of the reproductive tract for fertilization and implantation Major Actions on: Minerals, Carbohydrates, Proteins, and Lipid Metabolism In men, Bone Spermatogenesis Behavior Physiological Effects