Reproductive

biochemistry
SYLLABUS
FSH (p. 628) , LH (p. 628) , Estrogen (p.626), progesterone (p. 627) and androgens (p. 625) : synthesis,
metabolism and functions.
Biochemical tests for infertility (p. 628):

VII

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 Biochemistry

VII

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 Reproductive

Past Questions: Sources

 Testis (cells of leydig)-major source
1. Describe briefly the functions of estrogens.
BIOCHEMISTRY
(5)[04, 02]
2. Describe the Biosynthesis and Mechanism of action of Androgens in human male are:
Testosterone. (2) [13]
 Testosterone
Sex Hormones  Dihydrotestosterone (DHT)
 Sex hormones are the hormones which are  Androstenedione
primarily secreted from the gonads i.e., primary sex  Dehydroepiandrosterone (DHEA)
organs in human either of sexes which are testes
 The later two are secreted mainly from
and ovaries.
adrenal cortex and ovaries.
 Also some amount of sex hormone is secreted from
zona reticularis part of the adrenal cortex. - Testosterone is mainly secreted from testis.

 Sex hormones are grouped in 3 categories as - Testosterone is peripherally converted to

follows: dihidrotestosterone either within male
i. Androgens reproductive tract or in peripheral tissues like
liver, skin.
ii. Estrogens
iii. Progestins - Androgens are steroid hormones which are
derived from cholesterol and are C 19
I. Androgens
compounds.
- These are the male sex hormones which
stimulate male characteristics.
Synthesis of all sex hormones (Androgens, estrogens, progesterone) [13]

Cholesterol
VII
Cholesterol desmolase

17 hydroxylase 17-hydroxy 17,20lyase

Pregnenolone DHEA
pregnenolone

3 dehydrogenase 3 dehydrogenase 3 dehydrogenase

17 hydroxylase 17-hydroxy 17,20lyase Andro

Progesterone stenedione
progesterone

Aromatase Dehydrogenase or
isomerase
Estrone (E 1)
Aromatase
16 hydroxylase 17-estradiol (E 2) Testosterone

Estriol (E 3) 5 -reductase

5-dihydrotestosterone

Transport and metabolism  In the blood about 2% remain free in plasma

 Testosterone after secreted from the cells of which is its active form and remaining of the
leydig is directly poured into the blood fraction binds maximum to the albumin and
stream. minimum to sex steroid binding globulin
(SSBG)
FAST TRACK BASIC SCIENCE MBBS and then transported to-625 -
target
 Biochemistry
distant organs.
 Locally testosterone binds to the androgen
binding protein from cells of sertoli to have
action on male genital tract.
 Peripherally testosterone in converted to
more active form dihydrotestosterone
especially in organs like prostate, liver and
skin by enzyme 5- reductase.
 Testosterone is metabolised in the liver and
excreted by conjugation in form of inactive
metabolite 17-ketosteroids (androsterone
and etiocholanolone) through urine.
Functions
i. Regulation of differentiation of male internal
and external genitalia.
ii. Stimulation of growth and development of
male internal and external genitalia.
iii. Stimulation of sexual hair development
(pubic hair male pattern) and development
of secondary sexual characters.
VII iv. Stimulation of sebaceous gland secretion.
v. Stimulation of erythropoietin synthesis
which leads to erythropoiesis.
vi. Anabolic effects i.e., positive nitrogen
balance and retention of Na +, K+, Ca 2+, PO 4-- -
and SO 4-- and H 2O.
vii. Stimulation of bone growth and closure of
epiphysis.
viii. Spermatogenesis.
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ix. Maintenance of secretion of sex glands.
x. Regulation of male behavioral effects
(testosterone from fetal testis stimulate
fetal brain for male psyche).
xi. Role in male libido.
xii. Stimulate growth of larynx and deepening of
voice.
xiii. Myotrophic effect i.e., helps in increasing
the muscle mass.
Mechanism of action of any of sex hormones [13]
 Sex hormones cross the cell membrane of
target cell and bind with receptor in cytosol
forming receptor hormone complex and
enter the nucleus through nuclear pore in
nuclear membrane and binds to hormone
responsive element (HRE) of DNA and
regulate in gene expression and they act as
transcription factor and related protein and
formed to act within the cell or out of cell.
II. Estrogen
- These are the female sex hormones which
stimulate female characteristics.
Source
 Major source - ovary (granulosa cell and
granulosalutea cell)
 Minor source - sertoli cells, Adrenal cortex,
placental cell (in pregnant women)
Estrogens in human female are:
  - estradiol
 Estrone
 Estriol - the source is not ovary.
- Estrogens are also steroid hormones which are
derived from cholesterol and are C 18 compounds.
Transport and metabolism
 Estrogens after secreted from the granulosa
cell and granulosalutea cells are directly
poured into the blood stream.
 Reproductive

 xv. Stimulate renal Na and water retention and

In the blood, in minor amount it remains free ADH secretion.
in plasma and bound with albumin.
 In contrast to testosterone it is combined
maximally with the SSBG in plasma and gets
transported to target distant organs.
 Estrogen is metabolised into the liver in form of
estriol which undergoes conjugation with
glucuronate or sulphate in liver itself and
excreted through urine as conjugated
estrogens.

Functions [04, 02]

i. Stimulation of growth of female internal
genitalia i.e., fallopian tube, uterus and
vagina.
ii. Growth of mammary gland ductile system,
stroma and also helps in deposition of fats in
the breast.
iii. Secretion of plentiful, thin cervical mucus.
iv. Stimulation of thin sebaceous gland
secretion. VII
v. Stimulation of endometrial proliferation
(stratum functionalis).
vi. Stimulation of bone growth and early closure
of epiphyses.
vii. Stimulation of granulosa cell LH receptor
formation.
viii. Increase progesterone receptors.
ix. Decrease serum cholesterol.
x. Increase serum high density lipoprotein
(HDL)

xi. Decrease glucose tolerance (i.e., antagonises

insulin)
xii. Increase production of clotting factors.
xiii. Increase thyroxin binding globulin (TBG),
SSBG and transcortin synthesis from liver.
xiv. Increase uterine sensitivity to oxytocin.

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 Biochemistry
xvi. Increase female libido.
xvii. Have role in female type of fat distribution
and development of other female secondary
sexual characteristics.
xviii.Increases uterine motility and fallopian
tubes motility and cilliary action.
xx. Role in vaginal epithelial cornification.
xxi. Pigmentation of areola.
III. Progestins
Source
i. Major source-
 Ovary- corpus luteum( thecalutea cells).
ii. Minor source
 Placental cells (in pregnancy)
 Testis
 Theca cells (ovary- graafian follicle)
Progestins in human female are:
 Progesterone-abundant and more
potent.
VII
 17 hydroxyprogesterone.
Progestins are C 21 compounds.
Transport and metabolism
 Progestins once poured to the blood stream
after secretion, is transported in the blood to
the distant target organs principally in bound
form with cortisol binding globulin i.e.,
transcortin.
 Also in trace they are either bound in
albumin or freely transported in active form
in plasma.
 Progestins are metabolised in liver either to
pregendiol or pregnetriol and excreted
through urine in form of conjugated
products.
 About 10% of progestins are excreted
through urine unchanged.
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Functions
i. Role in production of secretory
endometrium.
ii. Stimulation is secretion of scant, viscous
cervical mucus which is hostile to sperm.
iii. Stimulation of mammary lobular alveolar
growth.
iv. Antagonism of aldosterone reaction (i.e.,
decrease sodium retention).
v. Increase body temperature (0.5°F) increases
thermoregulation set point.
vi. Decrease uterine motility (i.e., decreases
response to oxytocin)
vii. Suppression of milk synthesis.
viii. Stimulates breathing (ventilation) i.e.,
decreases alveolar PCO 2.
ix. Decreases of estrogen receptors.
x. Increases the secretion of whole female
genital tract.
- Vaginal mucus to prevent vaginal
cornification
- Cervical mucus
- Fallopian tube secretion to nourish
zygote.
xi. Progesterone contributes to growth and
development of fetus by acting as a
precursor for corticosteroid synthesis by the
fetal adrenal cortex.
Follicle stimulating hormone (FSH) and
luteinizing hormone (LH)
- Both FSH and LH are collectively known as
gonadotropins which are secreted from the
gonadotrophs of anterior pituitary gland.
- Chemically these gonadotrophs both are
glycoproteinious in nature with two subunits
namely  and .
 Reproductive

-  Subunit is identical in both - Sperm concentration 20-200 million per

hormones with 89 amino acids where as  ml of semen.
subunit differs with 112 aminoacid sequence in
FSH and 115 amino acid sequences in LH.
- In males, LH is called as interstitial cell
stimulating hormone (ICSH).
Functions
- FSH
 Males
 It helps in spermatogenesis by
stimulation of primary spermatocytes to
undergo 1st division of meiosis to form
secondary spermatocytes.
 FSH enhances the production of ABP
(androgen binding protein) by cells of
sertoli.
 Females
 It helps in development, maintenance
and maturation of graafian follide.
- LH
VII
 Males
 LH act upon leydig cells of testis to
produce testosterone which helps in
spermatogenesis.
 Females
 Helps in maturation (final) of graafian
follicle.
 It helps in ovulation.
Biochemical tests for infertility
For males

a. Semen analysis : Most important test for

assessing male fertility.
- It is analyzed by looking for following
parameters.
- PH = 7.5 - 8.0

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 Biochemistry

- % motility > 50% - FSH: 2-18 mIU/ml

- Motile sperm count > 10 million /ml - Estradiol:< 50 pg/ml
- White blood cells < 1 million/ml  Also TFT can be carried out.
- Morphology > 30% normal forms. For females
- Besides this semen should be looked for  Hormonal analysis : The hormones analysed
coagulation and liquefaction after are as follows:
coagulation and time taken for it.  FSH
b. Hormonal analysis: The hormones analysed  LH
are:
 Prolactin and
- Testosterone: 300-1100 mg/dl
 Thyroid function test (TFT) for TSH, free T
- Prolactin: 7-18 mg/ml
3 and T 4.
- LH: 2-8 mIU/ml
 Estradiol.

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 Reproductive

SPECIAL POINTS FOR MCQs

1. Of the androgens, the most potent is dehydrotestosterone and least potent is dehydroepiandrosterone (DHEA).
2. All the enzymes involved in synthesis of steroid hormones is microsomal except cholesterol desmolase of 1st
step which is rate limiting step, is mitochondrial enzyme.
3. Testosterone is excreted as 17-ketosteroids through urine.
4. Urinary 17-ketosteroids are mainly the metabolite from the adrenal androgen thus reflects adrenocortical
activity.
5. In fetal life differentiation of male internal and external genitalia is stimulated respectively by testosterone and
dihydrotestosterone.
6. Men are muscular and RBCs count is higher due to testosterone which has myotrophic effect and stimulate
eryoporetin.
7. Major estrogen in post menopausal women is estrone.
8. Estriol is the estrogen not produced from ovary but from placenta and liver.
9. Least potent estrogen is estrone.
10. Estrogen helps in thin sebaceous secretion which is less viscous so opposes testostesore causing acne.
11. Progesterone plays no role in development of female characteristics.
12. Testosterone, estrogen and progestins are respectively C19, C18, and C21 compounds respectively.
Testosterone is converted to DHT by 5  reductase. [MCQ 13]
13.
VII

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