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PREGNANCY PROTEINS

PREGNANCY PROTEINS. Early pregnancy factor (EPF) Placental proteins: pituitary-like hormones: hCG, hPL, ACTH, hCT hypothalamic-like hormones: GnRH, CRH, TRH, SRIF growth factors: inhibin, activin, IGFs, EGF other peptides: SP-1, PAPP-A, PP-5 Decidual proteins: PRL, relaxin, IGFBP, PP-14

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PREGNANCY PROTEINS

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  1. PREGNANCY PROTEINS • Early pregnancy factor (EPF) • Placental proteins: • pituitary-like hormones: hCG, hPL, ACTH, hCT • hypothalamic-like hormones: GnRH, CRH, TRH, SRIF • growth factors: inhibin, activin, IGFs, EGF • other peptides: SP-1, PAPP-A, PP-5 • Decidual proteins:PRL, relaxin, IGFBP, PP-14 • Fetal proteins:AFP

  2. HUMAN PLACENTA

  3. Early pregnancy factor (EPF) • immunosupressive protein produced by maternal ovaries stimulated by PAF • earliest known indicator of fertilization (48hr) • maximum production 0- 4 weeks then  • function: • prevents rejection of an embryo (binds to lymphocytes) • growth factor (?) • clinical applications : to be evaluated

  4. HUMAN CHORIONIC GONADOTROPIN (hCG) • glycoprotein hormone, two chains • alpha-subunit (chromosome 6) : identical • beta-subunit (chromosome 19) : unique activity and specificity • trophoblastic tissue (syncytiotrophoblast) • normal placenta (also multiple placenta) • gestational trophoblastic disease (hydatiform mole and choriocarcinoma;  x 3-100) • ectopic pregnancy

  5. hCG levels during pregnancy

  6. HUMAN CHORIONIC GONADOTROPIN (hCG) • control of secretion: placental GnRH secreted by cytotrophoblast ( activin, inhibin) • normal pattern of secretion : •  8 days post conception, dbl time 2-3 days • peak value 8-10 wk. of gestation ( 120,000 IU/L) •  and reach plateau  20,000 IU/L at 18-20 wk. of gestation •  in multiple pregnancy • at 1,000-1,500 IU/L intrauterine gestation visible with TVG ultrasound

  7. HUMAN CHORIONIC GONADOTROPIN (hCG) • determination: • biologic assays • immunologic: • radioimmunoassay (RIA, sensitivity 5mIU/ml) • immunoradiometric assay (IRMA, sensitivity 150mIU/ml) • ELISA (sensitivity 25-150mIU/ml) • fluoroimmunoassay (sensitivity 1mIU/ml) • latex agglutination inhibition tests (urine) • radioreceptor assay • high sensitivity pregnancy tests (<1mIU/ml) - sometimes false positive because of endogenous pituitary hCG

  8. FUNCTION OF hCG • maintains corpus luteum • stimulates: • progesterone production by the corpus luteum • Leydig cells of male fetus to produce testosterone (?) • fetal adrenal steroidogenesis • immunosupressive (lymphocyte modulator) • thyrotropic activity • induction of ovulation

  9. HUMAN PLACENTAL LACTOGEN (hPL)HUMAN SOMMATOMAMMOTROPHIN (hCS) • single chain polypeptide • produced 3 wk. post conception; detected in serum 5-6 wk. post conception • highest levels III trimester, disappears after delivery • production proportional to placental mass • determination: RIA

  10. Role of hPL during pregnancy

  11. HUMAN PLACENTAL LACTOGEN (hPL)HUMAN SOMMATOMAMMOTROPHIN (hCS) Growth hormone (GH and PRL-like effects) : • induces lypolysis,  plasma FFA • inhibits glucose uptake and gluconeogenesis, glucose intolerance • insulinogenic effect ( insulin) • hyperinsulinemia •  plasma IGF-I

  12. CORTICOTROPIN RELEASING HORMONE (CRH) ADRENOCORTICOTROPIN (ACTH) • produced in cytotrophoblast (max. at term) • stimulates placental ACTH release •  circulating maternal levels • structurally similar to pituitary ACTH •  circulating maternal levels • hypercortisolism

  13. DECIDUAL PROLACTIN (PRL) • similar to pituitary prolactin • regulates fluid and electrolyte flux through fetal membranes • secreted independently of fetal/maternal dopaminergic control • ALSO maternal and fetal pituitary PRL • maternal serum PRL  (100-200ng/ml) • AF PRL  until 20wk. (1000ng/ml) then 

  14. PLACENTAL PROTEIN 14 (PP14) • immunosupresive peptide • secreted in decidualized endometrium • circulating marker of decidual growth ALPHA-FETALPROTEIN (AFP) • synthesized in YS, GI and fetal liver • osmoregulator of fetal intravascular volume •  AFAFP and MSAFP in neural tube defects •  MSAFP in pregnancies with Down syndrome

  15. PREGNANCY STEROIDS • Estrogens: • estradiol • estriol • estrone • Progestogens: • progesterone • 17alpha-OHprogesterone • Adrenocorticoids: • cortisol

  16. ESTRIOL • 1000 x more than in non pregnant state • 90% of all estrogens in pregnancy • exclusively produced by placenta (conversion of 16alpha-DHEA-S) - only living fetus • detectable at 9th wk. (0,05ng/ml) ; at term (30ng/ml) ESTRADIOL / ESTRONE • produced by maternal sources (estradiol-ovaries: 5-6 wk.; estrone-ovaries, adrenal: 4-6wk.), gradually placenta, after I trimester major source (conversion of circulating DHEA-S) • after conception range 5-30ng/ml

  17. MATERNAL PLASMA UNCONJUGATED ESTROGENS Estradiol Estriol Estrone

  18. ESTRIOL • extremly low levels or no estriol: • fetal demise, anencephaly • CAH • placental sulfatase deficiency • hydatidiform moles • decline in estriol production or failure to rise: • maternal renal disease, PIH, preeclampsia or eclampsia • IUGR • large quantities: • multiple pregnancy • Rh isoimmunisation

  19. ESTROGENS - HORMONAL FUNCTION • augment uterine blood flow • placental steroidogenesis: regulation of progesterone synthesis • parturition: • ripen the cervix • initiate uterine activity • augment established labor • sensitivity of myometrium to oxytocin

  20. PROGESTERONE • production during pregnancy: • corpus luteum (only source till 6th wk.) • placenta (6th wk. -> 12th wk. -> parturition ) luteoplacental shift: 7-8th wk of pregnancy • production independent of fetus • conception cycle: sustained slow rise • early pregnancy: 10-35ng/ml, 100mg/day • at term: max. 100-300ng/ml, 250mg/day

  21. MATERNAL PLASMA PROGESTERONE

  22. PROGESTERONE - HORMONAL FUNCTION • modulates tubal motility (preimplantation conceptus) • inhibits maternal-fetal tissue rejection • antagonizes estrogen-augmented uterine blood flow • induces uterine relaxation (stabilization of lysosomal membranes and inhibition of PG production)

  23. Steroidogenesis in fetus & placenta

  24. OVARIANSTEROIDOGENESIS

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