Estrogens, Progestins, Hormone Therapy：estrogens激素治疗，孕激素，和.ppt

Estrogens, Progestins, Hormone Therapy Lorelei Vandiver Chem 5398 March 25, 2008 Outline Estrogens History Synthesis Receptors Medical Uses Progestins History Synthesis Receptors Medical Uses Hormone Therapy Menopause Types of HT Steroid Synthesis Estrogens Roles in both males and females Males: growth spurt, skeletal maturation, epiphyseal closure, maturation of sperm. Females: development of female sex organs and secondary sex characteristics, regulate menstrual cycle, skeletal maturation The most prevalent forms of human estrogen are estradiol and estrone. Both are produced and secreted by the ovaries, although estrone is also made in the adrenal glands and other organs. Estrogen History 1900: Knauer found that ovarian transplants prevent symptoms of gonadectomy. 1923: Allen and Doisy devised a bioassay for ovarian extracts. 1925: Frank and associates detected an active sex principle in the blood of sows. 1926: Loewe and Lange discovered that a female sex homone varied throughout menstrual cycle. 1928: Zondek reported excretion of estrogen during pregnancy. 1929: Estrogen crystallize by Butenandt and Doisy 1941: FDA approval of estrogen therapy for menopausal symptoms. Estrogen Synthesis - in the body Estrogen Receptors 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 binding sites called estrogen receptors. There are two estrogen receptors that are normally found in the cell’s nucleus: ER α and ER β. Estrogen Receptors cont. The receptor changes conformation due to the dissociation of heat shock proteins after estrogen binds to it. The receptor undergoes dimerization in order for increased affinity to DNA. This estrogen-receptor complex can now bind to specific DNA sites, called estrogen response elements (EREs). Genes are activated to produce messenger RNA, which guide the synthesis of new proteins, determined by the cell type.