Hormones produced by the placenta

Dr. Arthur Amit Suryakumar

28/10/2020

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 Overview

• Introduction about placenta

• Hormones released of placenta

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 Placenta anatomy & physiology
03/18/2023
https://ibiologia.com/placenta/ 3
 Placenta

• It grows throughout pregnancy and is normally delivered

through birth canal after the birth of baby
• Function
• Keeps maternal and fetal circulation separate
• Nourishes the fetus
• Eliminates fetal wastes
• Produces hormones vital to pregnancy
• Its approx weight at birth is 500 gms

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• The cytotrophoblast is the stem cell for the
multinucleated syncytiotrophoblast 
• Cytotrophoblast
• produce IGF-1 & 2, growth factors, H-hCG, estradiol,
progestrone
• Syncytiotrophoblast
• produces both protein and steroid hormones which are
released into the maternal blood 
• Human chorionic gonadotrophin (hCG) is produced
immediately after implantation of the blastocyst into the
uterine wall
• At eight weeks of gestation assumes the role of the
corpus luteum and begins to secrete the steroid
hormones
• LDL receptors are localized to syncytiotrophoblast
18/03/2023microvilli 5
 List of hormones produced by placenta

• The placenta produces

• Protein hormones
• hCG
• Placental lactogen
• Steroid hormones
• Estrogen
• Progesterone

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 Other hormones produced by placenta

• Adrenocorticotropin releasing hormone (ACTH)

• Cortisol releasing hormone (CRH)
• Gonadotropin releasing hormone (GnRH)
• Thyrotropin
• Growth Hormone releasing hormone (GHRH)
• GH variant (hGH-V)
• Neuropeptide YY
• Parathyroid releasing protein (PTH-rp)
• Inhibin
• Activin
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 Peptide hormones

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 Human chorionic gonadotropin

• It contains two subunit α and β subunit

• It is linked non-covalently, electrostatic and hydrostatic
forces
• It is exclusively produced by placental synctiotrophoblast
• It has the highest carbohydrate content of all human
hormones
• Sialic acid is present in the carbohydrate end protecting it
from degrading
• Its T ½ 36 hrs

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 Structure- hCG
α subunit β subunit
Structure 92 amino acids 145 amino acids
2 carbohydrate side 6 carbohydrate side
chains chains
5 disulfide bridges 6 disulfide bridges.

Molecular 14,900 Da, of which 23,000 Da

mass 10,200 is the protein
component

Synthesis continues to increase peaks at about 8 to 10

due to the mass of the weeks’ gestation and
placenta then decreases

Note : A single gene located on chromosome 6 encodes the α subunit

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of all four glycoprotein hormones (TSH, LH FSH, and hCG).
 Structure

18/03/2023 Glycan Analysis as Biomarkers for Testicular Cancer.. Michal Hires 12

et..al
18/03/2023 https://www.labpedia.net/pregnancy-test-beta-hcg-hcg/ 13
 Structure- hCG contd..

• The hCG carbohydrate composition changes as pregnancy

progresses
• Ist few weeks – Hyperglycosalted hCG
• Fourth week – serum concentration decline rapidly
• Ther are variants
• Nicked hcg (hcgn)
• Free α subunit (hcgα)
• Free β subunit (hcgβ)
• Nicked free β subunit (hcgβn)
• Beta core fragment

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 Biosynthesis & secretion

18/03/2023 https://www.labpedia.net/pregnancy-test-beta-hcg-hcg/ 15
 Regulation of synthesis and secretion

• The production of hCGβ in the syncytiotrophoblasts

• paracrine control of gonadotropin-releasing hormone
produced in cytotrophoblasts
• Cytotrophoblasts also produce inhibin, which stimulates
hCG production.

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 Mechanism of action

• It binds to and activates the LH receptor in cells of the

corpus luteum

• An increase in intracellular cyclic adenosine monophosphate

• The cAMP increase in turn stimulates the production of

progesterone – preventing menses and thus facilitates
pregnancy

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 Function

1. Rescue and maintain corpus leuteum- continue

progesterone function

2. Stimulation of fetal testicular testosterone secretion

3. Stimulate relaxin secretin from corpus leuteum

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 Function

4. Maternal thyroid gland stimulated by large quantities of

hCG- hyperthyroidism

• LH/HCG receptors are present on thyocytes

• It can be used to treat in hypothyroidism in male
• Modifications in hCG oligosaccharides
• Acidic isoforms-thyroid activity increase
• Basic isoforms – iodine intake increased

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 hCG-H

• hCG-H is produced by cytotrophoblast cells while regular

hCG is made in syncytiotrophoblast cell
• it is an autocrine acting directly on the cells which produce
it, while regular hCG is an endocrine acting on maternal
corpus luteal cells
• It has minimal biological activity in promoting progesterone
production compared to regular hCG.
• It is a invasion promoter, choriocarcinoma and testicular
germ cell malignancies, or as in implantation of pregnancy.

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 hCG-H

• It is an essential component for successful human

implantation to prevent early pregnancy loss and
spontaneous abortion.
• It is critical for promoting the midtrimester hemochorial
implantation, and for preventing preeclampsia.

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 Function

Human Chorionic Gonadotrophin: New Pleiotropic Functions for an “Old” Hormone During Pregnancy.,  Virginie Gridelet et.al
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 Metabolism

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New Discoveries on the Biology and Detection of Human Chorionic Gonadotropin.. Laurence A Cole
 Metabolism

• hCG beta core fragment is the terminal degradation product

of hCGβ –
• 73–amino acid
• two pieces of the β-subunit,
• residues 6–40 and residues 55–92
• held together by disulfide bridges.
• hCG beta core fragment is detected only in urine

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 laboratory evaluation of function

https://www.labpedia.net/beta-hcg-level-%CE%B2-hcg-human-
18/03/2023 chorionic-gonadotropin-hcg/ 26
 laboratory
evaluation of
function
Low in ectopic
pregnancy due to
improper placental
development

18/03/2023 http://perinatology.com/calculators/betahCG.htm 27
 Uses

• Hcg measurements in normal and abnormal pregnancies

• A potential biomarker for preeclampsia
• A serum marker for down’s syndrome screening
• Diagnosis of gestational trophoblastic disease
• Used in assisted reproductive technology

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 Placental lactogen

• It is a single – non glycosylated polypeptide

• It has similar to sequence of hGH
• It has 67% similarity structure to hPRL
• It is represented by chr 17 ( 5 genes GH-PL gene cluster)

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 Structure

Somatolactogens and diabetic retinopathy. Kevin bermea.et.al

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 Biosynthesis & secretion

• Initially it is produced by cytotrophoblast and later it is

produced from synctiotrophoblast
• Near term it is present produced 1 g/d
• T ½ - 10- 30 min
• It is secreted in the maternal blood
• Very less detected in fetal blood/ mothers urine/ amniotic
fluid

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 Regulation of synthesis and secretion

• hPl is
• Stimulated by insulin, IGF- 1
• Inhibited by PGE2 and PGF2α

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 Function

• Promotes lipolysis -- ↑ circulating FA level – energy source

• Maternal metabolism
• Fetal nutrition
• It decreases insulin sensitivity leading to increase glucose
level in mother
• The glucose is spared for fetal use
• enhancement of nitrogen retention amino acids
• prevents gluconeogenesis
• It is potent angiogenic hormone

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 Function

The Roles of Placental Growth Hormone and Placental Lactogen in the Regulation of Human
18/03/2023 Fetal Growth and 34
DevelopmentS. Handwerger, et.al
 laboratory evaluation of function

• Late pregnancy concentration is 5 to 15 µg/mL

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 Pregnancy associated plasma protein A

It is zinc containing metalloproteinase glycoprotein

It is expressed in low concentration in all tissues
In placenta the PAPP-A protein and mRNA are found in high
concentration
It has a role as a insulin like growth factor binding protein
protease
• It regulates action of insulin like growth factor 2 by cleaving
its binding protein and increase bioavailable forms

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 Clinical significance – PAPP-A

• low concentration
• In first trimester
• Down syndrome
• High rate of fetal loss
• Fetal growth
• Premature delivery
• Hypertension and pre eclampsia
• In second trimester
• cornelia di Lang syndrome

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 PAPP-A is also found in

Colon
kidney
endometrium
ovary
fibroblast
• vascular smooth muscle cells
• Osteoblast

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 Inhibin A

• It is a member of transforming growth factor beta

superfamily of proteins
• Placenta produces large quantities of inhibin that
completely suppresses FSH
• It is closely related to actvins
• They are also expressed in granulosa cell of ovary and sertoli
cell of testis
• It is produced by fetoplacental unit beginning in early
pregnancy

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 Inhibin structure

It is protein dimer of dissimilar subunits Alpha and beta linked

by disulfide bridges
The beta subunit past 2 types
•

• The activin contains of just beta subunits

18/03/2023 https://en.wikipedia.org/wiki/Activin_and_inhibin#/media/File:Activin_inhibin.png 40
 Inhibin A -uses

It is used as a marker for Down syndrome screening

• It is also used as a marker in ovarian cancer and evaluation
of male infertility

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 Placental GnRH

• It is highly expressed in 1st trimester

• It is found in cytotrophoblast
• It regulates the trophoblast hCG production
• Causes increased maternal GnRH

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 Placental CRH & urocortin

• Intrapartum increase 100- 500 pmol/L

• It increases more during labor
• It is also produced from membranes and decidua
• CRH receptors( CRH R1 and CRH R2)are present in many
tissues (Placenta)
• Urocortin also secreted by placenta but less than CRH

• Function: CRH and Urocortin both promote placental

secretion of ACTH

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 Placental Ghrelin

• It peaks at mid pregnancy

• It is a paracrine regulator of differentiation of cells
• It regulates hGH secretion

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 Pituitary like hormones

hGH- variant
• hGH hPL gene cluster on chromosome 17
• 191 amino acids differ in 15th amino acid position from
sequence for hGH
• Growth promoting an anti lipogenic function
• Decrease diabtogenic and lactogenic function
• Synthesised – synctiotrophoblast 21 or 26 weeks
• rises till 36 weeks and remains constant

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 Relaxin

produced by corpus luteum / decidua / placenta

Single 105 amino acids reproduction cleave to A & B
Structurally similar 2 insulin and IGF-1
H2 and H3 gene - corpus luteum
H1 and H2 gene – decidua , placenta and membrane
• Function
• Act on myometrium promote relaxation
• Enhance GFR
• Autocrine & paracrine roll in postpartum regulation of
extracellular remodelling
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 PT hrp

Significant elevation in maternal circulation

• it is found in normal adult tissue
• myometrium
• endometrium
• corpus luteum
• lactating memory issue
• important function is to regulate genes involved in
transfer of calcium and other solutes
• contributes to fetal mineral homeostasis in bones amniotic
fluid and fetal circulation

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 Steroid hormones

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 Estriol -Structure

• Estriol is an estrogen with hydroxyl groups at positions 3, 16,

and 17
• In late pregnancy this estrogen predominates
• strongly bound to sex hormone–binding globulin

Somatolactogens and diabetic retinopathy. Kevin bermea.et.al

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Estrogen-Biosynthesis &
secretion

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 Estrogen -Associated disorders

• Any disruption in the biosynthetic pathway will lead to very

low maternal serum uE3.
• Conditions that cause disruption include
• fetal anencephaly
• placental sulfatase deficiency
• fetal death
• chromosome abnormalities
• molar pregnancy
• Smith-Lemli-Opitz syndrome

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 Estrogen -Associated disorders

• Placental sulfatase deficiency- infant as X-linked ichthyosis

• It is present in approximately 1 in every 2000 males

• It is because of the lack of uE3
• delayed onset of labor and
• Cesarean section rate is significantly higher in these
mothers

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 Estrogen -Associated disorders

• SLOS is a serious, rare birth defect --inborn error in

cholesterol metabolism, 7-dehydrosterol-7-reductase
deficiency

• Down syndrome leads to a modest decrease in uE3

Note :Screening for Down syndrome is now the most common

application of uE3 measurements

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 Placental -Progesterone

• In pregnancy placenta becomes the major source of this

hormone
• Cholesterol is the main precursor for placental progesterone
• The production rate
• leuteal face 30 mg/d by corpus luteum
• By 3rd trimester it reaches approximately 300 mg/d
secreted by placenta

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 Progesterone

18/03/2023 http://sitn.hms.harvard.edu/flash/2018/pee-pregnant-history-science-urine-based-pregnancy-tests/ 55
 Progesterone functions

• Appropriate development of endometrium

• Uterine growth
• Adequate blood supply
• Preparation of uterus for labour

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 Glucocorticoids

• CRH gene expression

• CRH --- Placental ACTH – fetal & maternal adrenal
glucocorticoid function – stimulation of placental CRH
expression

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 Down’s syndrome screening-

18/03/2023 http://ck5354.blogspot.com/2012/06/testing-for-down-syndrome.html 58
 Down’s syndrome screening- Biochemical
markers

• 1st trimester
• Maternal serum markers
• PAPP-A 65% 85%
• Free beta HCG 60-
• Fetal Marker – nuchal thickness 75%

• 2nd trimester
94%
• Maternal serum markers
• AFP
triple test 70 %
• E3 76% quadruple
test
• hCG
• Inhibin A
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 References

• Tietz textbook of clinical chemistry and molecular

diagnostics, Nadir rifai et..al, 1st south Asian edition., 2018
• Williams obstetrics [edited by] F. Gary Cunningham..et.al ,
25th edition, 2018
• Williams Textbook of Endocrinology, Shlomo Melmed, et..al
,14th Edition, 2020

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• Thank You

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