pregnancy proteins early pregnancy factor (epf) placental proteins: –pituitary-like hormones: hcg,...
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PREGNANCY PROTEINSPREGNANCY 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
HUMAN PLACENTAHUMAN PLACENTA
Early pregnancy factor (EPF)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
HUMAN CHORIONIC GONADOTROPIN HUMAN CHORIONIC GONADOTROPIN (hCG)(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
hCG levels during pregnancyhCG levels during pregnancy
HUMAN CHORIONIC GONADOTROPIN HUMAN CHORIONIC GONADOTROPIN (hCG)(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
HUMAN CHORIONIC GONADOTROPIN HUMAN CHORIONIC GONADOTROPIN (hCG)(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
• 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
FUNCTION OF hCGFUNCTION OF hCG
HUMAN PLACENTAL LACTOGEN (hPL)HUMAN PLACENTAL LACTOGEN (hPL)HUMAN SOMMATOMAMMOTROPHIN (hCS)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
Role of hPL during pregnancyRole of hPL during pregnancy
HUMAN PLACENTAL LACTOGEN (hPL)HUMAN PLACENTAL LACTOGEN (hPL)HUMAN SOMMATOMAMMOTROPHIN (hCS)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
ADRENOCORTICOTROPIN (ACTH)ADRENOCORTICOTROPIN (ACTH)
• structurally similar to pituitary ACTH
circulating maternal levels
• hypercortisolism
CORTICOTROPIN RELEASING HORMONE (CRH)CORTICOTROPIN RELEASING HORMONE (CRH)
• produced in cytotrophoblast (max. at term)
• stimulates placental ACTH release
circulating maternal levels
DECIDUAL PROLACTIN (PRL)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
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
• Estrogens:– estradiol– estriol– estrone
• Progestogens:– progesterone– 17alpha-OHprogesterone
• Adrenocorticoids:– cortisol
PREGNANCY STEROIDSPREGNANCY STEROIDS
ESTRIOLESTRIOL• 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 / ESTRONEESTRADIOL / 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
MATERNAL PLASMA MATERNAL PLASMA UNCONJUGATED ESTROGENSUNCONJUGATED ESTROGENS
Estradiol
Estriol
Estrone
• 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
ESTRIOLESTRIOL
ESTROGENS - ESTROGENS - HORMONAL FUNCTIONHORMONAL 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
PROGESTERONEPROGESTERONE
• 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
MATERNAL PLASMA PROGESTERONEMATERNAL PLASMA PROGESTERONE
• 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)
PROGESTERONE - PROGESTERONE - HORMONAL FUNCTIONHORMONAL FUNCTION
Steroidogenesis in fetus & placentaSteroidogenesis in fetus & placenta
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