Placental Hormones Flashcards
Human Chorionic Gonadotropin
Act via
Plasma membrane LH-HCG receptor
Human Chorionic Gonadotropin
After 5 weeks of gestation it is produce by
Syncytiotrophoblast
Human Chorionic Gonadotropin
Beta HcG is also produced in the
Fetal kidney
Human Chorionic Gonadotropin
Also secreted by trophoblastic neoplasm and use as
Tumor marker
Human Chorionic Gonadotropin
Found in very small amount in tissue of
Men and non pregnant woman
Human Chorionic Gonadotropin
Release HCG less than 5 weeks
Cytotrophoblast and
Syncytiotrophoblast
Human Chorionic Gonadotropin
> 8 weeks release by
Syncytiotrophoblast
Human Chorionic Gonadotropin
Plasma half life of
36 hours
Human Chorionic Gonadotropin
Composed of alpha ____ and beta ____ sub units
Alpha 92
Beta 145
Human Chorionic Gonadotropin
Alpha sub unit is structurally identical with
LH
FSH
TSH is related to H-mole
Human Chorionic Gonadotropin
Single gene is located at
Chromosome 6
Human Chorionic Gonadotropin
Of the 7 genes
6 genes for beta HCG
1 gene for beta Lh
Human Chorionic Gonadotropin
Both sub units are synthesized and cleaved by
Endopeptidases
Human Chorionic Gonadotropin
Assembled and rapidly released by
Excocytosis of secretory granules
Site of HCG synthesis
HCG mRNA for both alpha and beta subunits are greater than at
Term pregnancy
Molecular form of HCG in plasma and urine
Free alpha subunits increase gradually and steadily until they plateau at
36 weeks
Molecular form of HCG in plasma and urine
Complete beta HCG molecule is maximal at
8-10 weeks
Concentration of HCG in serum and urine
Intact HCG is detectable in plasma of pregnant women
7-9 days after the mid cycle surge of LH that preceded ovulation
Concentration of HCG in serum and urine
HCG enters maternal blood at the time of
Blastocyst implantation
Concentration of HCG in serum and urine
Evidence of HCG levels doubles within
48-72 hours
Concentration of HCG in serum and urine
Peak maternal plasma levels between
69-80 days of menses
2-3 months of LMP
Concentration of HCG in serum and urine
Begins to decline at
10-12 weeks and undetectable in the serum by 16 weeks AOG
Concentration of HCG in serum and urine
Principal urinary form is the
Beta core fragment
Higher maternal plasma HCG levels
Multi fetal pregnancy Erythroblastosis fetalis Fetal hemolytic anemia Gestational trophoblastic disease Down syndrome Syphilis Big placenta
Lower HCG plasma levels
Early pregnancy
Ectopic pregnancy
Renal clearance of HCG accounts for
30 percent of its metabolic clearance,
Remainder is likely cleared by metabolism in the liver
Clearance of beta and alpha subunit are about
10
30 fold
Both HCG subunits are required for binding to the
LH HCG receptor in the corpus luteum and the fetal testis
Most important function of HCG is
Maintenance of function of corpus luteum (progesterone production ) in early pregnancy
HCG acts an LH surrogate to stimulate replication og
Leydig cells and testosterone synthesis
To promote male sexual differentiation
HCG promotes what? To promote uterine vascular vasodilatation and myometrial muscle relaxation.
Remain secretion
Human placental lactogen
Prolactin like activity secreted by
Anterior pituitary gland
Human placental lactogen
Immuno chemical resemblance to
Human growth hormone
Human placental lactogen
Detected as early as
2nd to 3rd week of fertilization
Human placental lactogen
Demonstrated in _________ before 6 weeks
Cytotrophoblast
Human placental lactogen
Chemical structures
191 AA residues
Structurally similar to human prolactin
Human placental lactogen
Located at
Chromosome 17
Human placental lactogen
Assess after 6 weeks postpartum for gestational diabetes
Increase concentration during pregnancy and post partum
Human placental lactogen
Detected in placenta within
5-10 days after conception
Human placental lactogen
Detected in maternal serum as early as
3 weeks
Human placental lactogen
Maternal plasma concentration are linked to placental mass and rises steadily until
34-36 weeks
Human placental lactogen
Half life
Between 10-30 minutes
Human placental lactogen
In the first half of pregnancy leads to an increase in hpl plasma concentration
Prolonged maternal starvation
Human placental lactogen
Stimulated by
Insulin
Insulin like growth factor
Human placental lactogen
Inhibited by
PGE2 andPGE2 alpha
Normally secreted by adipocytes
Leptin
Leptin
Synthesized by
Cytotrophoblast
Syncytiotrophoblast
Leptin
Inhibit
Apoptosis and promotes trophoblastic proliferation
Leptin
Function
Anti obesity
Regulate bone growth and immune function leptin
Neuropeptide Y
Localized in
Cytotrophoblast
Neuro peptide Y
Causes
CRH release
Inhibin
Acts to inhibit
Pituitary FSH release
Inhibin
Produced by
Human testis
Ovarian granulosa cells
- corpus luteum and trophoblast
Inhibin
Maternal serum levels peak at
Term
Inhibin
Inhibit
FSH secretion
Ovulation during pregnancy
Inhibin
Act via GnRH to regulate placental
HCG synthesis
Expressed in the placental and amnion
No detectable in fetal blood before labor but is present in umbilical cord blood after labor begins
Declines rapidly after delivery
Activin
Progesterone
Corpus luteum
Progesterone
> 8 weeks AOG produced by
Placenta
Progesterone
Normal production rate in pregnancy women
250 mg
Progesterone
In multi fetal pregnancies it may exceed
600 mg/ day
Progesterone
Placental progesterone production
Cholesterol converted to
Pregnenolone within mitochondria catalyzed by
Cytochrome p450
Progesterone
After canalizations by cytochrome p450. It is then converted to
Progesterone in endoplasmic reticulum by
3 beta hydroxysteroid dehydrogenase
Progesterone
Released through the process of
Diffusion
Progesterone
Placenta relies on
Exogenous cholesterol for progesterone production
Progesterone
Principal precursor
Cholesterol maternal
Progesterone
Uses LDl cholesterol for progesterone biosynthesis
Trophoblast
Estrogens relies principally on
Fetal adrenal precursor
Progesterone
During pregnancy there is an increase in plasma concentration of
5 alpha dihydroprogesterone
Progesterone
Also converted to
Potent mineralocorticoid deoxycorticosterone in pregnant and in fetus
Primary hormone during proliferative phase
Estrogen
Estrogen
First 2-4 weeks of pregnancy rising HCG levels maintain production of
Estradiol in maternal corpus luteum
Estrogen
Decrease significantly at
7 weeks
Lutheal phase transition
Estrogen
Most potent estrogen in the system
Estradiol
Estrogen
Estradiol production within the corpus luteum of non pregnant as well as early pregnancy
Luthenized theca
Granulosa cells
Estrogen
Not expressed in human placenta - conversion of C21 to C19 steroid is impossible
Steroid 17 alpha hydroxylase
Estrogen
Obligatory precursor of estrogen
C19 steroid
Estrogen
Placenta gas a high capacity to convert C19 to
Estrone and estradiol
Estrogen
Acted upon by 3beta-hydroxysteroid dehydrogenase type 1 to produce androstenedione
DHEA
Estrogen
Converts androstenedione to estrone which is converted to 17 beta hydroxysteroid dehydrogenase type 1
Cytochrome p450 aromatase
Estrogen
It is found that woman who had anencephalic fetuses has a
Very low estrogens level of about 10%
Estrogen
Anencephalic fetus need
Folic acid
Vit B12
Estrogen
Principal precursor for placental estradiol synthesis
DHEA-S
Estrogen
Most important source of placental estrogen
Fetal adrenal glands
Estrogen
To prevent neural tube defect how many folic acid
400 mg
Estrogen
More than 90% of estradiol and estriol formed enters
Maternal plasma
Estrogen
85% or more of placental progesterone enters
Maternal plasma
Estrogen
Steroids secreted from syncytiotrophoblast can enter maternal blood directly unlike when hormones enter
Blood
Human chorionic gonadotropin
Biological activity similar to
luteinizing hormone