OB: Placental Hormones – Dr.

RCJ  There is excessive proliferation of trophoblastic cells, meaning the

By: KhaChiLea (MD2018) production of hCG exceeds in compare with the normal value in normal
pregnancy
FORMS AND TYPES OF HORMONES  That’s why hCG compared with normal pregnancy and GTD, the amount
 Steroids of concentration is too much high in GTD
o Estrogen and Progesterone  hCG is found in very small amount of tissues of men, non-pregnant women
 both produced by placenta during pregnancy  the detection in the blood and urine is always indicative of pregnancy; that’s
 produced by ovaries in non-pregnant state why, when you test for pregnancy in pregnancy kit, you advise the patient to
 during pregnancy, the ovaries will stop secreting these hormones provide specimen like urine because is used determine if the patient is pregnant
 it is the role of the placenta that will secrete the progesterone and the  remember that positive pregnancy test is considered as PRESUMPTIVE sign of
function of your fetus to secrete the estrogen pregnancy not positive
o Aldosterone  It is a glycoprotein; highest in CHO content of any human hormone
o Deoxycortisone  Plasma HL is 36 hours; it stays in the system for almost 3-4 weeks
o Cortisol  Composed of alpha and beta sub-units
 Protein o but considering the importance, it is the beta subunit of hCG is requested
o Human Chorionic Gonadotropin (hCG) and clinically significant
o Human Placental Lactogen (hPL) o most of the time when we request quantitative determination of hCG, we
o Adenocorticotropin always request for the quantitative amount of BETA SUBUNIT OF HCG
o Growth Hormone Variant  Alpha subunits are structurally identical with LH, FSH and cross reacts with TSH
o Parathyroid Hormone-related Peptide while the Beta subunits are structurally related to LH
o Calcitonin
o Relaxin BIOSYNTHESIS OF HCG
o Inhibins  Single gene that is located on chromosome 6 encodes the ALPHA SUBUNITS
 Hypothalamic Releasing/Inhibiting Hormone common to hCG, LH, FSH and TSH; seven genes on chromosome 19 encode for
o Thyrotropin-releasing Hormone BETA-HCG-Beta LH family
o Corticotropin-releasing Hormone  HCG is not only available in endogenous form, there is form that we can used
o Somatostatin this for fertility work-up
o Growth Hormone Releasing Hormones  This hormone can be used as a drug that can be usually given for fertility
problem
HUMAN CHORIONIC GONADOTROPHIC HORMONE  Both subunits are synthesized as larger precursor, which are then cleaved by the
 Protein hormones that contains 2 subunits such as alpha and beta subunits endopeptidases
 Is considered as pregnancy hormone  Intact hCG is then assembled and rapidly released by secretory granule
 If you have hCG in the system, you are definitely pregnant exocytosis
 Biological activity is similar to LH; and acts via the plasma membrane of LH, hCG  IMPORTANT TO NOTE:
receptor o <5 weeks AOG
o Menstrual Period Phases Released and produced by both syncitiotrophoblast and cytotrophoblast
 Proliferative o 8-10 weeks AOG
 Ovaries will secrete the estrogen Exclusively produced by Syncitiotrophoblast
 Endometrial glands and stroma will proliferate Peak secretion of hCG
 Midcycle you have LH surge o After 12 weeks
 Secretory Will decline; normal pregnancy or normal fetuses, the concentration of
 Second part of cycle hCG particularly the b-hCG will become undetectable in NORMAL
 Ovaries will secrete progesterone to support secretory phase pregnancy
 Slouching of the endometrial debris called Menstruation  mRNA concentrations of both alpha and beta subunits in the syncitiotrophoblast
 The LH in this phase is very much evident are greater than at term, that’s why hCG is one of the biochemical markers to
o Remember that the first day of menstruation is considered to be as the first assess or diagnosed cases such as:
day of the cycle o Trisomy 21
 Kaya when we ask patient about the last menstrual period, it should be o Trisomy 18
the first day of the last menstrual cycle o Trisomy 13
 This LMP (first day of the last menstrual period) will help us to compute  When you request hCG for the detection of trisomy, it is usually detect at
the AOG of the fetus and of course the Expected Date of Confinement the 2nd trimester of pregnancy; therefore after the 12 weeks AOG
 Kelan po ang unang araw ng huling regla? nd
 2 trimester usually starts from 14wks-28wks
 Always remember the first day of the last menstrual period  But we usually request this hCG between 16th-201th of AOG for the
 REMEMBER: Based on LMP, we can use to compute for the AOG and EDC detection of the said conditions
 During the earlier part of the pregnancy, the hCG is being produced and  Increase hCG beyond 12 weeks, patient may have
secreted both by syncitiotrophoblast and your cytotrophoblast  Patau – Trisomy 13
 Syncitiotrophoblast is considered to be as the trophoblastic cells of the placenta  Edward – Trisomy 18
o Presence of the trophoblastic cells means that the patient is pregnant;  Down – Trisomy 21
Outcome maybe as follows:  When to request?
 Pregnancy if you have normal trophoblastic cells  Maternal Age (35 and above)
 Trophoblastic cells coming from abnormal will result to abnormal type of  Beta-subunit hCG are low or undetectable throughout the pregnancy that’s why
pregnancy it can be used as specific detection of trisomy 21, 13, 18; it will be detectable
o If it is secreted by your trophoblastic neoplasia particularly the Hydatidiform within 8-12 weeks and become undetectable after that.
Mole  Alpha subunits are consistent and plateau all throughout the pregnancy
 As mentioned, when you have hCG both of the serum and urine of the  Once you have a decrease production of hcG, this is the time for your estrogen
patient means that the patient is pregnant but regardless of the outcome and progesterone rises
of pregnancy still there is hCG in the system like H-mole o 7-9 days
 Also known as Gestational Trophoblastic Disease; in case of this, the  Intact/combine hCG molecule is detectable in plasma of pregnant women
patient is pregnant but unfortunately there is no development of fetus after the midcycle surge of LH precedes ovulation
 HCG enters the maternal at the time of BLASTOCYST implantation
 Doubling time of hCG is 2 days/48 hours
 o ECTOPIC PRENANCY 3. Cross reacts or same biological act of THYROID SIMULATING HORMONE
 Intrauterine pregnancy is the normal; if you have ectopic or extrauterine that’s why if there is excessive HCG parti in cases of HMOLE the pt will also
gestation, the fertilize egg can be implanted on the cervix, fallopian tube present with hyperthyroidism in 30% of the cases
or in the ovaries; while the implantation of fertilized egg in in your
abdomen is considered as Abdominal Pregnancy HUMAN PLACENTAL HORMONE
 The production of hCG does not meet the normal increase as compared  Prolactin like act
Intra-uterine pregnancy  Potent lactogen and GH like bioactivity
 Normally, If you have IU pregnancy with 100,000 hCG, you expect that the  Detected 2 or 3 weeks of fertilization
nd rd

value will become double after 48 hours  FXN

 In case of ectopic pregnancy, when you have an initial level then there is o Promote lactation
no doubling concentration after 48 hours because environment is not o IG F prod
suitable for implantation o Glucocorticoid prod
 NORMAL INTRAUTERINE PREGNANCY, NORMAL PROD OF HCG, NORMAL o Ca transport
DOUBLING TIME, if there is ectopic pregnancy there is a decline or a decrease in o Peripheral insulin resistance
doubling time of 48 hours  During preg: there is resistance in insulin, this resistance is dec in the
uptake of glucose in peripheral areas of body that’s why preg is
PEAK MATERNAL PLASMA OF HCG considered as diabetogenic
 Reach 100000 from 16th day to 18th day of menses, and it will decline for 10 to  Promotes lipolysis, proteolysis;
12 weeks and becomes undetectable during pregnancy  when you re assess of cases of GDM it will be (+) but after pregnancy yoh
 The HCG appears in the fetal blood same on the maternal side of about 3% have to reassess if the pt has only GDM, or the pt has existing DM prior to
 The principal urinary form or the terminal degradation, and when you request preg
for pregnancy test, use the URINE bec it is the fragnments of HCG wc is the  reassessment is done 6th wk post partum, bec youy one to get rid of
major form in urine HPL before you evaluate the reassessment
 EXTRACTED BLOOD- can also used as a form of pregnancy test o 75g OGTT
o FROGS TEST- bec the urine or the plasma of pt is injected into FROGS and  Kaya pag buntis it is mandatory: to screened for GDM, more spec if you
after 24 to 48 hours you must dissect the frog and look for the follicles I the are FILIPINA
ovary, and if there is follicles it means that there is a sufficient amount of  Recommended and not selective
HCG that will stimulate changes in ovary  FILIPINAS has highest incidence of GDM in ASIA
Malalaman mon a yung pt mo ay pregnant after 24 to 48 hours  CHARACTERISTICS:
DIFFERENT FACTORS THAT WILL INCREASE LEVEL OF HCG o Gene structure and expression
1. Fetus that are considered trisomies 21, 13, 18 expect that the value of HCG o In the plasma after 5 to 10D AFTER conception
is increase on the 2nd tri of preg based on MOM (multiple of median)  METABOLIC ACTIONS:
a. Ex you req for 16 weeks, at 16th weeks of gestation, the concentration of o Maternal lipolysis
HCG is consistent particular to your AOG, this is based primarily in the o Inhibit leptin secretion by term trophoblast
multiple of median, once your HCG concentrations are released in the lab, o Anti-insulin
that’s why it is very important for the clinicians to be specific in the AOG, by  Diabetogenic inc GDM risk
the time he is requesting for HCG determination o Formation of fetal vasculature
2. H-MOLE excessive prolif of trophoblastic cell inc in the concentration of
HCG OTHER PLACENTAL HORMONES
a. B HCG: req as prognostic fx for cases of H mole, bec once you read the  Relaxin
trophoblastic cell, you must also check your B HCG level from time to time  Growth hormone
for 1 year, be you might be dealing from malignant form of gestational  Parathyroid
trophoblastic dse GESTATIONAL TROPHOBLASTIC TUMORS
3. ERYTHROBLASTOSIS FETALIS HYDROPS FETALIS (immune or non immune) Hypothalamic LIKE RELEASING HORMONE
a. They have this very big placenta Inc in HCG DIRECTLY PROPORTIONAL  Coticotrophin
b. GESTATIONAL DM  gonadotrophin
c. SYPHILITIC INFXN IN PREG
d. They will have a very big placenta so expect a higher level of HCG OTHER PEPTIDE HORMONES
4. MULTIPLE PREGANCY
 LEPTIN
a. Twin pregnancy you will have a bigger placenta
 Inhibin
 Activin
DECREASE IN CONCENTRATION OF HCG
 Neuropeptide
 ECTOPIC PREG
 Steroid hormones
 MISSED ABORTION- early pregnancy wastage
o The most important is progesterone and estrogen
o In laymans, since ovary is not fxning during pregnancy; they believe that eg
ABORTION- expulsion of the product of conception prior to 20 wks AOG
and pg are absent in the system, but in contrary the highest concentration is
seen during preg
BIOLOGIC FXN OF HCG
Progesterone produced by the placenta
1. Remnants of egg from the follicles will bec the CORPUS LUTEUM
Estrogen produced by fetal adrenals
o Corpus luteum will stimulate prod of PROGESTERONE to maintain the Early
PROGESTERONE
forms of placenta or pregnancy
o HCG is primarily prod in the placenta, in early preg this hCG will stimulate  <8 wks: prod by CL
corpus luteum Cl will be the source of PROGESTERONE in early part of  >8wks of AOG/ 2mos- placenta assumes progesterone secretion
pregnancy  THREATENED ABORTION or PRETERM LABOR- clinician will give exogenous
th
o PROGESTERONE secretion and prodxn takes place around 8 wks of AOG progesterone
th
 But before 8 wks it is the fxn of the ovary particularly CL stimulated HCG o Can be in form of oral, inserted intra vaginally
to prod PROGESTERONE  Hormone that is protective and preventive for further complication
o Max secretion of HCG at 8 to 10 wks then will stimulate further CL to  FIRST TRIMESTER- you have to assess for suspicious enlargement of mass in the
secrete PROGESTERONE TO MAINTAIN PREG ovary, especially during early pregnancy we usually do not do anything, bec
2. Stimulate LH to stimulate the replication of leydigs cell to promote male sexual when you remove that mass and it turns out to be it is the CL
differentiation o And remember that CL maintain pregnancy
o When you remove this before than 8 wks you wil have preg wastage
 o Postpone to 16th to 18th wks before you excise the tumor, bec the prod and
secretion of progesterone is at max
 MULTIFETAL PREGNANCY it exceed 600ml per day
 In multiple pregnancy, there is 600ml per day and remember the primary source
of progesterone would action will coming from cholesterol (maternal
cholesterol)
 Maternal cholesterol is the primary precursor for progesterone synthesis
 HCG is produced and secreted by the trophoblastic cells, unlike progesterone it
needs precursor and chemicals coming from the maternal system esp
cholesterol, kaya nga yung mga buntis na matataba mas maganda ksi maadami
source of proge
 LDL is one particular form of chole (aka bad chole), so nature has its own way of
getting away bad cholesterol kaya dapat magbuntis ka
 LDL chole is the primary precursor of proge
DIFFERENT RXNS GOING IN PROGESTERONE SYNTHESIS
 As much as 90% of maternal chole has found to be the principle precursor of
proge biosynthesis (use the bad chole)
o Proge is the hormone resp for maintaining maternal pregnancy
 ESTROGEN will lies on your fetal adrenal precursor, and is another very
important hormone
o Intensity of E2 is uncomparable
o E2 is considered to be the hormone resp for the fetal well being
 During pregnancy there is an increase plasma concentration of the 5-alpha-
dehydroprogesterone and the progesterone is converted to potent
mineralocorticoids deoxycorticosterone in pregnant women and in the fetus
 NOTE: BIOCHEMICAL RXN: you have cholesterol from maternal source (LDL)
used to produce progesterone and progesterone can also be used to produce
aldosterone and cortisol, on the other hand there is testosterone converted to
estradiol. It is not only progesterone that is being produced from cholesterol. In
this reaction you can have aldosterone, cortisol, estradiol and testosterone on
the system. Primarily for maternal synthesis of placenta and fetal adrenals
ESTROGEN
 KING?
 Placenta is reach in proge, estro and hcg
 Placenta can make the skin smooth (kaya nga madaming cream na palcenta etc)
bc placenta is reach in hormones
 Remember: is produced from maternal and fetal glands particularly adrenal
glands, that’s why during intrauterine life there are three basic & essential
organs:
o BRAIN – syempre kapag hindi nadevelop hindimagiging matino yung bata
o HEART – walang magiging function ang brain kundi tumitibok ang heart
o ADRENALS – is considered to be very imp tbc it is the one that produce E2
and E2 will be the homone that gives fetal well being
 During pregnancy, the patient is more specifically feel female fetuses, with
hyper estrogenic states that terminate abruptly after delivery. (proge prod from
placenta; E2 produced from adrenals). Kaya nga dun sa mga fetus na babae,
there is a blood tinge in their vagina during delivery that is due to hyper
estrogenic state during intrauterine that will be abruptly mawawala yan bc
there is no blood supply from placenta to the fetus which are expected due to
hypoestrogenic state
 First 2-4 weeks of pregnancy, take note rising HCG concentration from the
placenta, and HCG stimulates corpus luteum to secrete estrogen in the form of
estradiol. (there are different forms and shapes of E2)
o FXN OF HCG
 Stimulate corpus luteum to produce progesterone
 Stimulate corpus luteum to produce estrogen in the fetus, bc the adrenal is
too small and immature to produce its own estrogen, until after there is
transition
 Decreasing significantly at 7th week if there is luteal phase transition (kanina
yung progesterone from corpus luteum is only good for 8 weeks, bc after that it
is the placenta that will produce the progesterone, and during 7th week it is the
fetus that will secrete estrogen). Amazing yan kaya ng ayung iba kapag 2 mos pa
lang dugo pa lang, but hindi nay an basta dugo, may baby na jan
 Forms of estrogen: Estradiol, Estrone and Estriol
PLACENTAL ESTROGEN BIOSYNTEHESIS
 Estradiol production within the corpus luteum of non pregnant women as well
as in early pregnancy continues to require interaction between the luteinized
theca and granulosa cells
 C19 steroid is the obligatory precursor for estrogen synthesis (kaya steroid yan,
bc steroids are responsible for placental well being)
 C19 steroid  placenta have high capacity to convert your c19 to estrone and
estradiol
 Placenta expresses high levels of steroid sulfatase (STS) which converts the
conjugated DHEA-s to DHEA. DHEA is then acted upon 3beta-hydroxysteroid
dehydrogenase type 1 to produce andronestenedione
PLAASMA C19 STEROIDS AS E2 PRECURSOR
 It Is found that in women which had anencephalic (mal development of cranium
– incompatible with life) fetuses have very low estrogen level of 10%
 Adrenal glands of anencephalic fetuses were found to be atrophic because of
the absence of hypothalamic-pituitary fxns which is responsible for the
stimulation of the adrenal glands (which occurs in anencephalic fetus need for
folic and vit b12)
 DHEA-S is the principal precursor for placental estradiol synthesis
 Fetal adrenal glands is the most important source of PLACENTAL E2
 From the maternal blood you have cholesterol, as mentioned earlier in the
synthesis, progesterone can be used to produce different type of
mineralocorticoid, and cholesterol can produce progesterone coming from the
placenta.
 And progesterone is also used by the fetal adrenal to convert DHEA and STS so
there is an addition of fetal sulfate from fetal liver and will be transported to the
placenta
 E2 secreted to the maternal circulation from fetal DHEAS converts to estriol in
the palcenta, that’s why when request for the second biochemical markers for
trisomy 21 you will request for the estrogen determination you are actually
requesting for the unconjugated estriol determination
 Kasi diba your estrogen di ka naman absta wpede tumusok sa adrenals, so by
invasive method get maternal blood. Ngayon high tech na just get fetal cells,
determining fetal abnormalities via maternal blood. Available in Singapore and
HKG, so if yu wanna engage for prenatal testing just get maternal blood. And
mother’s blood can also be used to determine if the mother will develop pre
eclampsia in the earlier or later part of pregnancy and risk for gestational
DM.not available in the Philippines, but wpede yan ishift ang blood to the other
countries.
 Available in the PH: unconjugated estriol determination, PAP-A (pregnancy
assoc plasma protein A), maternal and fetal AFP
 Fetal adrenals is the primary source of fetal estrogen
 Estrogen is the primary placental estrogen secretory product occur. But
remember that the unconjugated estriol is the one being requested
 Near term, fetus is the primary source of the 90% of the placental estriol and
estradioll precursor in human pregnancy. If means if you have normal level of
estrogen you have a normal pregnancy
 For HCG, dba sabi natin nagincrease ng 8-10, nagdecline ng 12, at tumaas on 2nd
trimester  TRISOMY 21 (down syndrome)
 For ESTROGEN: when you request for biochemical markers request them one at
a time, hcg, estriol, papa and afp.
o Unconj estriol determination for T21  DECREASE from multiples of
median
o Unconj estriol determination for anencephalic cases  DECREASE kasi there
is loss of the hypothalamic pit stimulation for the prdxn of E2
 STS deficiency & Placental fetal aromatase deficiency – production is affected,
especially in males and this is a very rare type of enzymatic disorder  causing
severe form utilization of mother and fetus.
 Metabolites DHEAS including androstenedione and testosterone are secreted in
the maternal an fetal circulation
 There is a delayed epiphyseal maturation, unfortunately we seldomly diagnose
those metabolic do due to lack of reagents & screenings
CONDITIONS AFFECTING ESTROGEN PRODUCTION
 We have cases of intrauterine fetal demise, fetal death in utero, or intrauterine
fetal death, so if you would request for estrogen conc, we know for the fact the
fetal adrenal is the source, so once if you have dead fetus, there is no blood
supply of the fetal adrenals, so expect that the value is decreased.
 As far as the progesterone secretion is concerned, you know for a fact that
progesterone is produced from the placenta, and the blood supply of placenta is
the uterine artery so continuous ang production ng progesterone
o Intrauteirne fetal demise (ligation of the umbilical cord) - normal or
increased in the production of progesterone, but abnormal and decreased or
undetected estrogen
 o Fetal anencephaly – bc of the hypothalamic-pit
o Fetal adrenal hypoplasia
 you have a miniature adult (abn pituitary fxn)
 cytomegalic form (nodular formation of eosinophilic cells in the fetal
zone)
o Trisomy 21 – hcg increase, unconj estriol decrease (low level of unconj
estriol is due to insufficient secretion coming from the fetus)
 Compatible with life
o Deficiency of fetal LDL chole – restricted formation in corpus luteum and
placenta
o Fetal erythroblastosis (immune/non immune) – severe fetal antigen
isoimmunization, estrogen levels in maternal plasma are elevated above
normal due to increase placental mass; accumulation of fluid, hydramnios;
ascites and pericardial effusion

MATERNAL CONDITIONS AFFEING PLACENTAL ESTROGEN PRODUCTION

 Glucocorticoid treatment – glucocorticoids inhibits ACTH: reduction in placental
estrogen formation
 Maternal adrenal dysfxn – mothers with addisons ds have decreased urinary
estrogen levels
 Gestational trophoblastic disease - you know for a fact the estrogen coming
from the fetal so secretion is decline or zero (low estrogen due to no fetal
adrenal source of c19 steroids)