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PREGNANCY PROTEINS

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PREGNANCY PROTEINS Early pregnancy factor (EPF) Placental proteins: pituitary-like hormones: hCG, hPL, ACTH, hCT hypothalamic-like hormones: GnRH, CRH, TRH, SRIF – PowerPoint PPT presentation

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Title: PREGNANCY PROTEINS


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 (lt1mIU/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
ADRENOCORTICOTROPIN (ACTH)
CORTICOTROPIN RELEASING HORMONE (CRH)
  • 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. -gt 12th wk. -gt 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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