Endocrine changes during pregnancy

Pregnant women experience adjustments in their

endocrine system
The most important endocrine changes are the
production of:
 human chorionic gonadotropin (β-hCG)
 Human placental lactogen (hPL)
Prolactin
progesterone and estrogen by the placenta.
Maternal hormone levels, which differ from those in
the nonpregnant state, are dependent on:
a.The presence of a placenta (a rich store of steroid and
protein hormones)

b.The presence of a fetus:

in the ♂ fetus the testes, in response to βhCG, produce
testosterone, which is necessary for normal male development.
In the ♀ fetus, normal development is not depend on fetal
ovarian steroid production

c.The presence of elevated levels of circulating estrogens

d.The ability of the placenta to regulate molecular transport by

permitting or restricting passage and transfer of oxygen and
nutrient from the mother to the fetus and metabolic wastes and
carbon dioxide from the fetus to the mother.
The presence of high level of estrogens have
the following affects:

1. They increase the effects of binding protein such TBG,

and CBG.

2. They partially inhibit the enzyme 3- β-hydroxysteroid

dehydrogenase.

3. They inhibit maternal pituitary gonadotropin synthesis

and release, thus making placental gonadotropins
responsible for gonadtropic function.
 Four characters.

1.Chemical nature

2.Source

3.Normal patterns

4.Significance
 Placental endocrinology

At 6-8 weeks there is transfer of functions of corpus luteum

to the placenta-which acts temporarily as a new endocrine
organ or power house of hormone production.

1. Chemical nature: hormones of the placenta:

Protein hormones (e.g. hCG, hPL, Prolactin, α-feto
protein [AFP])
Steroid hormones (e.g. estrogen, progesterone, fetal
adrenal steroids).
2. Source
a. The placenta: the placenta play a major role as an endocrine organ
and is responsible for the production of both protein and steroid
hormones including: hCG and hPL. At the end of the 1st trimester the
placenta produces a large quantities of progesterone along with many
releasing and inhibiting hormones, such as GnRH, CRH, and TRH.
b.The mother: is an exclusive source of the certain hormones in the
early first trimester,. However, as the pregnancy progress the fetus
produces , thyroid substance, pituitary tropic hormones, and gonadal
steroid.
c. Fetus; the fetus is also involves in many of the processes of
hormones production and in this capacity the conceptus functions as
a unit involving both fetus and placenta.
d.Multiple source: such as estriol is produced by the mother , the
fetus and the placenta
3. Normal patterns. Recognizing normal patterns of hormones
activity during pregnancy can help distinguishing abnormal
pregnancies and fetal compromise.

4.Significance. Understanding the function of a particular hormone

may illuminate its rule in reproductive physiology, particularly in
maintaining pregnancy and fetal well-being; for example, hormone
deficiencies that are deleterious to the pregnancy can be corrected by
exogenous hormones, and the presence of certain hormones may
serve as markers for gestational abnormalities.
a. High levels of hCG suggest a trophoblastic neoplastic disease
because hCG originates in trophoblastic tissue.
b. Progesterone deficiency early in pregnancy suggests corpus luteum
insufficiency because progesterone is produced by the corpus luteum
in early pregnancy.
 Hormones of the Placenta and their
Cytochemical Origin
HYPOTHALAMIC-LIKE(RELEASING) CYTOCHEMICAL ORIGINE
HORMONES

Corticotrophin releasing CRH) Cytotrophoblast

Gonadotrophin releasing +
(GnRH)
Thyrotrophin releasing(TRH) +

Growth hormone +
releasing(GHRH)
 Hormones of the Placenta and their
Cytochemical Origin
PITUITRAY-LIKE(RELEASING) SYNCYTIO
HORMONES

Adenocorticotrophic hormone Syncytiotrophoblast

(ACTH)

Human chorionic +
gonadotropin (hCG)

Human chorionic +
Thyrotrophin (hCT)

Human placental lactogen +

(hPL)
 PROTEIN HORMONES
Protein hormones are similar but not necessarily
identical with those produced by the pituitary. For
example placental lactogen is chemically similar to both
pituitary growth hormone and Prolactin, but biological
activity of placental lactogen is much inferior than
Prolactin or growth hormone produced by pituitary.
The main site of production of the placental hormones is
the trophoblast of the chorionic villi.
 PROTEIN HORMONES
Human chorionic Gonadotrophin
Human placental lactogen
Pregnancy specific β-1 glycoprotein (PSβ-1G)
Cytokines
growth hormone [GH]
insulin-like growth factors [IGF's]
corticotrophin releasing hormone [CRH]
 vascular endothelial growth factor [VEGF]
placental growth factor [PIGF])
Pregnancy associated plasma protein or PAPP-
A
 HUMAN GONODOTROPIN HORMONE
•  HCG is secreted by the syncytiotrophoblast into the
maternal blood, where it maintains the endocrine
activity of the corpus luteum (i.e., synthesis of
progesterone during the early stages of pregnancy).
• It can be detected in maternal serum as early as day 8
after conception.
• Levels of hCG rise throughout the early stages of
pregnancy and reach their maximum level at week 8 of
gestation. By week 13, the level drops dramatically and
reaches a low steady state. By this time, the placenta
itself produces enough progesterone to support
pregnancy.
 HUMAN CHORIONC GONADOTROPIN
(hCG)
A. Chemical nature. Is a glycoprotein with molecular weight of
approximately 35,000 daltons ~(36000-40000 daltons) and
composed of two dissimilar side chains. The α-subunit(92 amino
acids) and a hormone specific β- subunit(145 amino acids)

1. The α-subunit is biochemically similar to Alfa subunit:

a. Luteinizing hormone (LH)
b. Follicle-stimulating hormone (FSH)
c. Thyroid-stimulating hormone (TSH)

2. The β-subunit is relatively unique or specific to hCG.

B. Source. It is produced by placental syncytiotrophoblast.
hCG is produced by trophoblastic tissue in the following
conditions.

1) Normal placenta tissue as early as 6 to 8 days

postconception as shown by immunofluoresence.
2) Multiple placental development (multiple gestation)
3) Hydatidiform moles by virtue of trophoblast
proliferation
4) Choriocarcinoma cells
5) Ectopic pregnancy.
C. Mode of determination. hCG levels can be measured by
biological, immunological assays and radioreceptor assays on
blood or urine.

D. Normal patterns.
 hCG rises rapidly 8 days postconception and first appearing
in the maternal blood 10 days after fertilization.
 doubling every 2 to 3 days and reaching a peak at
approximately 80 days (10 to 12 weeks),
 dropping to a plateau after 15 weeks at (20-22 wks) and
reaching a steady state for the remainder of pregnancy.
 hCG is detectable throughout pregnancy.
 hCG is increased in the multiple gestation.
• E. Significance.

a. Maintain corpus luteum production of progesterone

until the placenta can take over maintenance of
pregnancy.

b. Regulate steroid biosynthesis in the placenta and

adrenal glands as well.

c. Stimulate testosterone production in the male tests

(leydig cells )
hCG determinations are used as :
1. A marker for pregnancy (pregnancy testing)
A. Inadequate level or low values early in pregnancy suggest poor
placental function and may predict:
 ectopic pregnancy
 threatened abortion or
 missed abortion.
B. Excessive level suggest:
 multiple gestation or
 trophoblastic neoplasia. (e.g. hydatidiform mole and
Choriocarcinoma), and embryonal carcinoma.
 Pregnancy with a21 trisomy fetus
2. To follow the course of patients treated for trophoblastic neoplasia.
3. hCG is used clinically for induction of ovulation to treat
anovulation based on its biological stimulating to that of LH
4. hCG has some TSH-like activates
 Mode of determination
• hCG levels can be measured by biological and immunological
assays and Radioreceptor assays on blood or urine.
Immunological assays are more specific and sensitive than
biological assays and, thus, have replaced them for routine
methods.
• Biological assays are of historic note only; they are not used
today because of the more specific and reliable immunologic tests.
• The Friedman rabbit test measures maternal hCG levels by its
ability to cause ovulation in rabbits 12 hours after administration.
• The male frog test measures sperm release into the ejaculatory
ducts in male frogs after administration of hCG.
• The Aschheim test- Zondek rat test measures ovarian follicular
development after exposure to hCG.
 Mode of determination
• Immunological assays
• Agglutination, or the latex particle fixation test, determines hCG
levels in urine. Several drops of patient’s urine are mixed with
antibodies to hCG, then latex particles coated with hCG are added
to the urine. If hCG is in the urine. It coats the antibodies. This is
the rapid assay and is positive in 95% of cases 28 days
postconception.
• Radioimmunoassay is used on blood specimens using antibodies
to the β-subunit of hCG. It is positive 8 days postconception.
• Radioreceptor assay measures the amount of hCG in blood that
competes with radiolabeled hCG for a given amount of receptor
sites on bovine luteal cell membranes. It is a rapid assay, but it is
not as specific as that on the hCG β-subunit radioimmunoassay.
 Functions of hCG hormone
• stimulus for the secretion of progesterone by the corpus
luteum of pregnancy
• Maintain corpus luteum production until the placenta can
take over maintenance of the pregnancy ( till 6 weeks of
pregnancy)
• stimulate testosterone production in the leydig cells of the
fetal male testes
• Regulate steroidogenesis or steroid biosynthesis both fetal
adrenal and the placenta as well.
• Stimulates maternal thyroid because of its thyrotrophic
activity
• It has got immuno-suppressive activity
• It inhibit the maternal process of immuno-rejection of the
fetus as a homograft.
 LEVEL OF THE HCG AT DIFFERENT
PERIODS OF PREG NANCY
• The half life of hCG is about 24 hours
• By radioimmunoassay it can be detected in the maternal serum or
urine as early as 8-9 days following ovulation
• The doubling time of hCG concentration in plasma is 1.4-2 days
• It reach maximum levels ranging 100IU and 200 IU/ml between
60-70 days of pregnancy
• The concentration falls slowly reaching a low level of 10-20 IU/ml
between 100-130 days
• There after it remains constant throughout pregnancy
• Slight secondary peak occur at 32 weeks
• Hormone disappears from the circulation within 2weeks following
delivery.
 HUMAN PLACENTAL LACTOGEN (hPL)
A. Chemical nature. hPL is a single chain protein hormone
with growth hormone and Prolactin-like effects (chemically
and immunologically similar to pituitary growth hormone
and Prolactin). its molecular weight is 22,000

B. Source and Normal patterns. hPL is formed by the

syncytiotrophoblast as early as 3 weeks postconception and
can be detected in maternal serum as early as 5-6th weeks
postconception, and disappears promptly from the blood
after delivery.
It has a half-life of approximately 15 minutes.
Pregnancy change—its level parallels placental growth,
rising throughout the pregnancy. So the plasma
concentration of HPL is proportional to placental mass.
The level rises progressively from 5micro gms/ml to
25micro gms/ml until about 36 weeks.
C. Mode of determination. hPL is measured by
radioimmunoassay.

D. Significance
• It induces lipolysis and elevates plasma free fatty acids, which
provide energy for the mother, conserving blood glucose for use
by the fetus.
• It induces insulin resistance and carbohydrate intolerance in the
mother (it decrease maternal tissue sensitivity to insulin resulting
in gestational diabetes )
• It inhibits glucose uptake and gluconeogenesis in the mother.
• It has an insulinogenic action, which elevates plasma insulin
level, favouring protein synthesis and ensuring a source of amino
acid for fetus.
Effect: It antagonizes the cellular action of insulin, decreasing
insulin utilisation , thereby contributing to the predisposition of
pregnancy to glucose intolerance and diabetes.

hPL determinations have been used to test placenta function;

however, fetal heart rate monitoring techniques are more reliable
and sensitive in assessing fetal well-being.

If levels are low :

Threatened abortion
Intrauterine growth retardation (IUGR)
 FUNCTIONS

• Antagonizes insulin action

• High level of maternal insulin helps protein
synthesis
• HPL causes lipolysis and proteolysis
• Promotes transfer of glucose and amino acids to
the fetus.
  
PROLACTIN

• A. Chemical nature. Prolactin is a protein hormone

with a molecular weight of 22,000

• B. Source. Three potential sources of Prolactin are:

1. Anterior lobe of the maternal pituitary gland.
Prolactin levels increase due to maternal pituitary
gland enlargement by 50%.
2. Anterior lobe of fetal pituitary gland
3. Decidual tissue of the uterus.
 PROLACTIN
C. Mode of determination. Prolactin is assayed by
radioimmunoassay of blood or amniotic fluid.

D. Normal patterns. Prolactin levels in the normal

nonpregnant female range between 8 and 25 ng/ml. levels
above this range are related to the following factors:
1. Ingestion of certain drugs that elevate Prolactin (e.g.
phenothiazines)
2. Hypothyroidism
3. Pituitary adenomas
4. Hypothalamic disease
PROLACTIN

E. Significance
• Prolactin prepares the mammary glands for lactation.
• Decidual Prolactin is thought to be important for fluid
and electrolyte regulation of amniotic fluid.
• Levels of Prolactin in pregnancy should not be
interpreted as indicative of pituitary adenoma growth.
However, patients with Prolactin-secreting adenomas
who conceive should be monitoring by visual field
determinations for the possibility of enlargement.
• Levels of Prolactin are markedly increased during
pregnancy. These levels paradoxically decrease after
delivery but later increase in response to suckling.
 PREGNACY SPECIFIC β– 1GLYCOPROTEIN
PS β– 1 G

• Produced by the trophoblast cells

• It can be detected in the maternal serum 18—20
days ovulation.
• PS β– 1 G is a potent immuno-supressor of
lymphocyte proliferation
• It prevents the rejection of the conceptus
 EARLY PREGNANCY FACTOR

• Early pregnancy factor (EPF)is a protein , produced

by the activated platelets and other maternal tissues.
• It is detected in the circulation 6 to 24 hours after
conception.
• It is an immuno-supressant and prevents rejection
of the conceptus.
 GROWTH FACTORS

• Inhibin , activin, insulin like growth factor,

transmitting growth factor β and epidermal growth
factors are produced by the syncytiotrophoblast
cells.
• Functions include,
• Immunosupressive
• Paracrine
• Steroidogenic.
 PREGNANCY ASSOCIATED
PLASMA PROTEIN

• A (PAPP-A) is secreted by the syncytiotrophoblast

• It act as an immunosupressant in pregnancy

 α-FETOPROTEIN (AFP)
A. source. A unique glycoprotein derived largely from the
fetal liver and partially from yolk sac.
• In early pregnancy (5-12 weeks), amniotic fluid AFP is
mainly from yolk sac origin.
• Maternal circulating AFP is mainly from the fetal liver
• Its function is unknown.
B. AFP is highly concentrated in the fetal central nervous
system (CNS) abnormal direct contact of CNS with
amniotic fluid (as with neural tube defects) result in
elevated amniotic fluid and maternal blood levels.
C. Elevated levels also are seen with intestinal obstruction,
omphalocele, congenital nephrosis, and multiple gestation.
 STEROID HORMONES

• OESTROGEN: The site of production is in

the syncytiotrophoblast
• Chemical nature: Estrogens are phenolic
steroids with 18 carbon atoms, characterized
by an atomic ring.
• Estriol is produced in large amounts during
pregnancy.
 ESTROGENS

A. Definition:
There are steroid hormones, which occur in three forms, each
of unique significance during a woman’s life :

1) Estradiol

2) Estriol

3) Estrone
 BIOSYNTHESIS OF ESTRIOL
• Maternal cholesterol is converted in by placenta to
pregnenolone and later to progesterone. Placental
pregnenolone together with fetal adrenal
pregnenolone is partly converted to pregnenolone
sulphate . pregnenolone sulphate is then converted by
fetal adrenals to dehydroepiandrosterone sulphate or
DHEA SO4 ,the most important precursor of placental
estrogens. This biochemical changes is produced by
hydrolysis of the sulphate to dehydroepiandrosterone
and conversion to androsterone, followed by
aromatization of estrogen.
 BIOSYNTHESIS OF ESTRIOL cont….
• DHEA SO4 of fetal adrenal origin is converted in the fetal
liver to 16- alpha hydroxy DHEA SO4 which is then
converted by placenta to estriol in two steps.

 Step 1: Sulphatase removes the so4 radical.

 Step 2: Aromatize converts the A ring to the phenolic
structure characteristics of estrogens.

• Thus the production of estriol involves the integration of

maternal , fetal and placental pathways.
• Estradiol, the most potent estrogen and predominant majority during
the nonpregnant reproductive years. It contains two hydroxyl groups
at the 3 position 3 and 17.
• It is converted from androgens (produced from cholesterol in the
follicular theca cells ), which diffuse into the glandulous cell
containing the Aromatase enzyme that completes the transformation
into estradiol.

2. Estriol : Is the mean estrogen during pregnancy, and accounts for

90% of the estrogens produced during pregnancy.
Dehydroepiandrosterone-sulfate (DHEA-S) from the fetal adrenal gland
is precursor for 90% of estriol converted by sulphates enzyme in the
placenta.

3.Estrone Is the mean from during menopause. Postmenopausal adrenal

androstenedione is converted in peripheral adipose tissue to estrone.
 LEVELS IN NORMAL PREGNANCY

• Estriol is first detectable at 9weeks (0.05ng/ml) and

increases gradually to about 30ng/ml at term.
 SIGNIFICANCE

• Normal estriol values signify fetal well- being.

• Estriol levels reflects placental functioning ability.
• Low estriol level indicates , fetal death, fetal anomalies
(adrenal atrophy, anencephaly, down syndrome),
hydatidiform moles, placental sulphatase or aromatase
deficiency.
• High levels are often associated with multiple pregnancy
and Rh- isoimmunization.
• Declining estriol levels or their failure to rise on serial
examinations are indicative of placental insuffiency
causing IUGR, PIH, maternal renal disease.
 PROGESTERONE

Before 6weeks of pregnancy the corpus luteum

secretes 17-hydroxyprogesterone. Following the
development of trophoblast it is synthesized and
secreted form placenta. The placenta can utilize
cholesterol as a precursor derived from the mother
for the production of pregnenolone and ultimately
progesterone.
 PROGESTERONE
A. chemical nature. Progesterone is ∆-4,3ketosteroid hormone
that contains 21 carbon atoms. It has two angular methyl
groups at the 10 and 13 positions and a two carbon side chain
at the 17 position.

B. Source.
In the nonpregnant state, progesterone is produced by all
steroid forming glands, including the ovaries, testes, and
adrenal cortex. It serves as an intermediary and precursor for
other hormones (e.g. testosterone, corticosteroids, and 17-
hydooxyl progesterone) and as an end- product when it is
produced by the corpus luteum.
• In the pregnant state, progesterone has a dual source:
a. it is produced exclusively by the corpus luteum up to the 6-7 wks
of pregnancy.

b. Between 7 and 9 both, corpus luteum and placenta produce

progesterone

c. after 9 wks the corpus luteum declines and progesterone

production is exclusively by placenta.

• This point is clinically significant because progesterone produced

by the corpus luteum is essential for pregnancy maintenance until
the eight week.
C. Mode of determination.
• Progesterone can be measured in the blood by radioimmunoassay
and competitive protein binding assay.
• Some laboratories may measure pregnanediol, the major
metabolite of progesterone, by 24- hour analysis

D. Normal patterns
 In a nonconception cycle, the progesterone peak reaches 25
mg/day, and levels measure approximately 20 to 25 ng/ml in
peripheral blood.
 the placenta produce 250 mg/day; most of the progesterone
produced enters the maternal circulation.
 A transient decline in peripheral blood progesterone levels has
been described in the 7 to 8wks of pregnancy, the time of the
luteo-placental shift; however, the subtle change can be
appreciated only when daily measurements are made.
D. Significance.
Progesterone has all of the following properties:

1. In early pregnancy it induces endometrial secretory changes

favourable for blastocyte implantation and it maintains the
endometrium

2. In later pregnancy its function is the induce immune tolerance

for the pregnancy and prevent myometrial contraction (relaxes the
myometrium)

3. It has natriuretic actions and, thus, stimulates the increased

production of aldosterone during pregnancy.

4. It serves as a major precursor for critical fetal hormones during

pregnancy.
LEVELS IN NORMAL PREGNANCY
• The average levels of progesterone at 12week ,
28week, and term approximate 25ng/ml, 80ng/ml,
300ng/ml respectively.
• Low progesterone levels are observed in ectopic
pregnancy and abortion.
• High values are observed in , hydatidiform mole,
Rh-isoimmunization.
• After delivery plasma progesterone level decreases
rapidly and is not detectable after 24 hours.
 FUNCTIONS OF STEROID
HORMONES

• Estrogen causes hypertrophy and hyperplasia of the uterine

myometrium.
• Progesterone in conjunction with estrogen stimulates growth
of the uterus.
• It causes decidual changes in the endometrium and inhibits
myometrial contraction.
• Hypertrophy and proliferation of breast ducts are due to
estrogen
• Both steroids are required for the adaptation of the maternal
organs to the constantly increasing demands of the growing
fetus.
FUNCTIONS OF STEROID HORMONES cont…

• Estrogen sensitises the myometrium to Oxytocin and

prostaglandins. Estrogen ripen the cervix.
• Progesterone along with hCG and decidual cortisol inhibits
T-lymphocyte mediated tissue rejection and protects the
conceptus.
• Together they cause inhibition of cyclic fluctuating
activity of gonadotropin-gonadal axis there by preserving
gonandal function
 Diagnostic value of placental
hormones
• Diagnosis of pregnancy
• Follow up cases who had trophoblastic tumors
• Detection of functions of feto-placental unit
• Main source of production is the corpus luteum of ovary,
but part of it may be produced by the placenta and decidua.
• Relaxin relaxes the symphysis and sacroiliac joints during
pregnancy and also helps in cervical ripening by its
biochemical effect.
 RELAXIN

• Main source of production is the corpus luteum of ovary,

but part of it may be produced by the placenta and decidua.
• Relaxin: relaxes the symphysis and sacroiliac joints
during pregnancy and also helps in cervical ripening by its
biochemical effect.
 Thyroid Physiology
• The maternal thyroid gland undergoes a number of
physiologic modifications to meet the metabolic demands of
pregnancy.

•  The diagnosis of thyroid disease during pregnancy requires an

understanding of the changes in thyroid physiology and
thyroid function tests that accompany normal pregnancy.

• To meet the increased metabolic needs during a normal

pregnancy, there are changes in thyroid physiology that are
reflected in altered thyroid function tests :
 Thyroid physiology 
• The major changes in thyroid function during pregnancy are:
1. An increase in serum thyroxine-binding globulin (TBG)
concentrations and

2. An increase in stimulation of the thyrotropin (TSH) receptor by

human chorionic gonadotropin (hCG).

N.B: hCG is one of a family of glycoprotein hormones, including

TSH, with a common alpha-subunit and a unique beta-subunit.
However, there is considerable homology between the beta-subunits of
hCG and TSH. As a result, hCG has weak thyroid-stimulating activity .

In a human thyroid cell-culture assay, as an example,

1 micro-U of hCG was equivalent to 0.0013 micro-U of TSH
 Maternal Thyroid Gland
• The thyroid gland enlarges slightly in up to 70 % of pregnant
women, because of its increased vascularity and glandular
hyperplasia; however, true goiter is not usually present.
• The percentage varying depending on iodine intake.
• In normal pregnancy the iodide levels in the mother decreased
due to increased urinary excretion of iodine and transfer
iodothyronines to the fetus. Because of that, thyroid gland
triples its uptake of iodide from the blood creating a relative
iodine deficiency which is probably responsible the
compensatory follicular enlargement of the gland.
 Maternal Thyroid Gland
• Estrogen levels cause an increase in thyroid binding globulin (TBG).
• Placental hormones such as hCG may also have thyroid-stimulating
proprieties, which lead to an elevation in total T3 and T4.
• Together, these changes lead to a relatively euthyroid state, although
free T3 and T4 levels may decrease slightly during pregnancy.
• Total thyroxine (T4) and tri- iodothyronine (T3) levels increase but
do not result in hyperthyroidism because there is a parallel increase
in T4-binding globulin that results from estrogen exposure.
• The increase seen in binding-protein concentrations is similar to that
observed in women who use oral contraceptives (OC). A modest
increase in the basal metabolic rate (BMR) rate occurs during
pregnancy secondary to increasing fetal requirements. Some T4 and
T3, but no TSH, are transferred across the placenta.
Maternal thyroid function during pregnancy
 CORTICOTROPIN-RELEASING HORMONE
• From mid-pregnancy, the trophoblast is capable of producing
corticotrophin-releasing factor (CRF) and this stimulates the
fetal pituitary to increase fetal adrenocortcotropic hormone
(ACTH) and thereby fetal dehydroepiandrosterone (DHEA)
production by the fetal adrenal is increased.
• DHEA is the main precursor for placental estrogen secretion.
• CRH levels is increased in the maternal plasma in the final
two trimesters of pregnancy but its biological effects are
diminished by high affinity of corticotrophin binding globulin
(CRH-BG).
• The concentration of the CRH-BG fall in the last 4-5 weeks of
pregnancy and, as a consequence, free levels of CRH appear to
rise.
 Metabolic Changes

• By the third trimester, maternal basal metabolic rate

is increased by 10 to 20 % compared with that of
the nonpregnant state.
• This is increased by an additional 10 % in women
with twin gestations.
• Total pregnancy energy demands are estimated to
be as high as 80,000 kcal or about 300 kcal/day
 Carbohydrate Metabolism
• Overall effect is that pregnancy is diabetogenic
• First half: tendency to hypoglycemia
• Second half: tendency to hyperglycemia

• Progressive insulin resistance as pregnancy progresses

• Progesterone
• Estrogen
• HPL
• “Typical” FBS less than in non-pregnant state
• Blunting response to meals, eating as pregnancy
progresses
• Hypertrophy of beta cells as well
 Glucose metabolism 
• Carbohydrate metabolism is very curial for the fetal
development because glucose is the major substrate for
fetal growth and nutrition.
• 1st half of pregnancy is characterized by mild fasting
hypoglycemia ~0.5-1mmol, postprandial
hyperglycemia, and hyperinsulinemia.
• Insulin secretion is increased in response to glucose and
amino acids.
• Hyperplasia and hypertrophy of beta cells of pancreas.
• Increased insulin level favours lipogenesis (fat storage).
This mechanism ensures continuously
supply of glucose to the fetus
Diurnal Glucose and Insulin
Changes in Late Pregnancy
 Changes in plasma protein
• During the 1st trimester the total protein
concentration falls ~ 1g/d, even though there is
nitrogen retention.
• This is partially due to:
1. Increased insulin concentrations
2. Placental uptake and transfer amino acids to the fetus for
gluconeogenesis and protein synthesis.
3. This fall is proportional to the fall of albumin
concentration and is associated with corresponding fall in
colloid osmotic pressure.
 Fat Metabolism

• An average of 3-4 kg of fat is stored during

pregnancy mostly in the abdominal wall, breasts,
hips and thighs.
• The total serum lipid rises about 600 to 1000mg
per 100ml.
• Fat is used as a source of energy and, glucose is
available for growing fetus.
 IRON METABOLISM

• Iron is absorbed in ferrous form from duodenum

and jejunum and released into the circulation as
transferrin.
• 10% of ingested iron is absorbed
• Total iron requirement during pregnancy is
estimated approximately 1000mg.
• In the absence of iron supplementation, there is a
drop in hemoglobin, serum iron and serum ferritin
concentration at term pregnancy.
 Calcium metabolism and locomotor
system
• Relaxation of pelvic ligaments and muscles occurs
because of the influence of estrogen and relaxtin
reaches maximum during last weeks of the
pregnancy.

• Increased number lordosis later months of the

pregnancy due to enlarged uterus backache and
wadding gait.