Endocrine Steroids 2. Signal transduction 3. Prostaglandins

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1 Endocrine Steroids 2. Signal transduction 3. Prostaglandins

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6 Estrogen Menopause (pause in the menes) ["change of life" at about 50] - lack of estrogen. (Some hysterectomy or ovarian cancer surgeries might also deplete because of ovarectomy). Many symptoms, hot flashes most obvious short term effect. Osteoporosis most obvious long term effect.

7 more estrogen (hormone) replacement therapy Hotly contested (a lot of negative press lately), partly because estrogen increases chances of breast cancer. There is a drug, Tamoxifen that blocks estrogen's effects, differently in different tissues.

8 Recent paper hormone therapy Estrogen and progesterone receptors in cardiovascular, neural, immune, gastrointestinal and musculoskeletal systems. Menopause (average age 51) vasomotor flashes, vaginal dryness, urinary symptoms, osteoporosis, CHD (coronary heart disease).

9 More on HRT paper (ET) for CHD and osteoporosis. A well intentioned study, WHI (women's health initiative) tested placebo, estrogen & estrogen-progestin. Discontinued because of increase in breasst cancer, CHD, stroke and venous thromboembolism (but they did decrease fractures and colon cancer)

10 More on ET 17beta-estradiol.(E2) AND estrone (E1) Study used conjugated equine estrogen (CEE) extracted from pregnant horse urine, many estrogens including sulfated estrogens. Why this matters is that there are several types of estrogen receptors differentially activated by different estrogens.

11 more Study used continuous oral administration hormone through hepatic portal system highly activates estrogen receptors in the liver, changing important proteins like angiotensin precursor. Transdermal patch would be very different. Women is study were fatter than usual.

12 finally Human progesterone vs study's medoxyprogersteone acetate (MPA), again affecting different receptors differently, also MPA activates glucocorticoid receptor. There are several estrogen receptors, alpha and beta. and many ways they influence transcription. "Antiestrogen" tamoxifen is antagonist in breast but agonist in bone and uterus, SERM (selective estrogen receptor modulator).

13 Androgens Anabolic steroids - muscle growth, bone growth, increased hemoglobin There is an androgen from the adrenal - DHEA dehydroepiandrosterone Increased secretion of testosterone at puberty has many obvious effects including on larynx Absence of androgens by castration decreases seminal vesicle and prostate

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18 5 alpha reductase When I typed "five alpha reductase" or the like into my search engine, I got hits on hair loss, concerning male pattern hair loss (androgenetic alopecia) accelerated by DHT and alleviated by a drug, Propecia

19 Weird disorders 5alpha-reductase deficiency -> "testes-attwelve" (at puberty, when there is enough testosterone to overcome deficit) There is a pedigree in the Dominican republic androgen receptor mutation (androgen insensitivity syndrome [AIS]) -> testicular feminization, children think they are females until there is no menstruation There are androgens from adrenal, so with Congenital adrenal hyperplasia, CAH, clitoris is large and behavior is "tomboy"

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21 Signal transduction "gene"sequence coding for protein (mrna) is copied from exons with introns spliced out "upstream" of gene, proteins binding promoter and enhancer regulate transcription

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26 Prostaglandins, etc mediators of inflammation derived from fatty acid (arachidonic acid, 20:4) cyclooxygenase (COX) leukotrienes (mediators of inflammation)... use lipoxygenase Prostaglandins have different actions in different places;

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28 More take platelet aggregation -- TXA2 stimulates clumping, PGI2 prevents them from sticking to walls of vessels; it is the TXA2 aspect that is why you take aspirin to prevent heart attack and should not take aspirin before surgery (etc.).

29 NSAIDS aspirin, ibuprofen, inhibit prostaglandin inhibit cyclooxygenase (COX-1 & 2) problems in stomach Celebrex, Vioxx, Bextra inhibit COX-2; popular for arthritus, increasing cardiovascular problems Aspirin is anti-inflammatory, analgesic, antipyretic, anticoagulant, implicated in Reye's syndrome.