1

hormones
2/25/14 Department of Biochemistry, Kathmandu Medical College
Chemical messengers

Types of chemical messengers: 3 types

1.Nervous system: secretes neurotransmitters

2.Endocrine system: hormones

3.Immune system: cytokines
Hormones
 Acts as a means of communication – cellular
communication
Biological function achieved by: 1. Nervous system –

transmission of electrochemical impulse

2. Endocrine system: wide range of chemical
messengers

Hormones: organic substance, produced in small amount

by specific tissue (endocrine glands)

Regarded as chemical messengers!!

4
Classification of hormones
Based on chemical nature

Protein or peptide hormones: insulin, glucagon,
antidiuretic hormones, oxytocin
Steroid hormones: glucocorticoids,
mineralocorticoids, sex hormones
Amino acid derivatives: epinephrine,
norepinephrine, thyroxine (T4), triiodothyronine
(T3)
Based on mechanism of action

Classified into 2 groups (based on location of the
receptor)
Group I & Group 2
Mechanism of action of steroid
hormones
7
Mechanism of action of group I
hormones

 Lipophilic in nature

Pass across plasma membrane  binds to intracellular

receptor (Site: cytosol/nucleus)  hormone-receptor
complex binds DNA (HRE)  expression of genes 
production of protein  action of hormone.
Mechanism of action of group II
hormones

Considered as first messenger

Exerts their action through intermediary molecules
Intermediary molecules  SECOND MESSENGERS

Second messenger: cAMP

Hormones
Hypothalamic hormones: TRH, CRH, GnRH, GRH, GRIH,
and Prolactin release-inhibiting hormone (PRIH)

Gonadotropin-releasing hormone (GnRH): stimulates

anterior pituitary  releases gonadotropins (Luteinizing
hormone (LH), Follicle stimulating hormone (FSH))
Hormones of Gonads
Gonads: testes in male & ovaries in female
Perform closely related dual functions
Synthesizesex hormones
Produce germ cells

Role: Growth, development, maintenance and regulation

of reproductive system.

 Primarily for development of germ cells.

Steroid hormones
5 steroid hormones Vitamin D
Precursor: Cholesterol
Glucocorticoids Steroid hormones
Mineralocorticoids
Androgens Bile salts
Estrogen
And Progestin

Synthesized by ADRENAL CORTEX, OVARIES,

TESTES, and OVARIAN CORPUS LUTEUM.
LH and FSH
LH

Group II hormone, binds to cell surface
receptor.
Secreted from anterior pituitary gland.
Stimulates synthesis of estrogen and
progesteron and causes ovulation
Promotes Androgen synthesis by testes.

FSH

Anterior pituitary gland.
Stimulates ovulation and estrogen synthesis.
In male: Promotes spermatogeneis.
Sex Hormones
 Categorized into three groups”
Androgen: male sex hormones: C-19 steroids

Estrogen: female sex hormone: C-18 steroids.

Progesterone: C-21 steroid, produced during the

luteal phase of menstrual cycle and also during
pregnancy

First two phage of menstrual cycle: follicular phase

Biosynthesis of steroid
hormones
Biosynthesis of steroid
hormones
ANDROGENS
Produced by LEYDIG CELLS of testes, minor amount by
adrenal glands in both sexes
NOTE: Ovaries also produce small amount of

ANDROGENS!!

Biosynthesis of ANDROGENS
Precursor: Cholesterol
Biosynthesis of ANDROGEN

Mostly occurs in
peripheral tissues
Biosynthesis of androgen
Naturally occurring androgens:
Testosterone,
Epiandrosteron, Androsterone,
Dehydroepiandrosterone (DHEA)

Common in these androgens: CH3 group at

C10 and C13 and all are C-19.
5 enzymes in 3 proteins:
1.3b-hydroxysteroid dehydrogenase & ∆5,4-
isomerase
2.17a-hydroxylase & C17,20-lyase
3.17b-hydroxysteroid dehydrogenase
 Physiological and biochemical
functions of androgens
 Sex related physiological functions:
androgen, primarily DHT and testosterone
influences:
growth, development and maintenance of male
reproductive organs
Sexual differentiation and secondary sexual
characteristics
Spermatogenesis
Male pattern of aggressive behavior
 Physiological and biochemical
functions of androgens
Biochemical functions:

ANDROGENS are anabolic in nature.

Effects on protein metabolism: promotes

transcription and translation
Cause positive nitrogen balance and increase
muscle mass

Effect on carbohydrate and fat metabolism:

increase glycolysis, fatty acid synthesis and
citric acid cycle.

Effect on mineral metabolism: promotes

mineral deposition and bone growth
Testosterone metabolites

Metabolic pathways: 2 pathways

1. Oxidation at 17-position: 17-keto steroid,
generally inactive
2. Reduction of A ring double bond and 3-
ketone: DHT
Metabolites of testosterone
Most potent: DHT

Sites: prostrate, external genital, and some areas
of skin

Plasma content: 1/10th. Of testosterone (400

mg/dl).

Reaction catalyzed: NADPH-dependent 5a-

reductase

5a-reductase: type 1 and type 2

Pseudohermaphroditism: mutation in type 2

Regulation of testicular
hormone
Testicular steroidogeneis: stimulated by LH
Binds to receptor on plasma membrane of Leydig
cells  activates adenylase cyclase  increase
intracellular cAMP  enhance rate of cholesterol
transport by STAR and side chain cleavage by
P450scc.

Spermatogeneis: regulated by FSH and

Testosterone
FSH binds to sertoli cells  ABP synthesized 
ABP secreted in lumen of seminiferous tubules 
testosterone produced by Leydig’s cells is
ESTROGENS
Predominantly ovarian hormones
Synthesized by follicles and corpus luteum of ovary.
ESTROGENS (contd.)
Responsible for maintenance of menstrual cycle and
reproductive process in women.

Synthesis of ESTROGENS
Precursor: Cholesterol
Produced by aromatization of androgens
Ovary: Produce Estrone (E1) and Estradiol (E2)
Placenta: E1,E2 and E3

Synthesis is under control of LH and FSH.

ESTROGEN
Physiological and Biochemical functions of
ESTROGENS

1. Sex-related physiological functions: growth,

development and maintenance of female reproductive
organs.

2. Maintenance of menstrual cycles

3. Development of female sexual characteristics

ESTROGEN (contd.)
Biochemical functions
Involved in many metabolic functions

 Lipogenic effect: increases lipogenesis in adipose

tissues

Hypocholesterolemic effect: lower plasma total

cholesterol
LDL fraction of lipoprotein is decreased, while HDL fraction is
increased

Anabolic effect: promotes transcription and translation, synthesis of

protein in liver is elevated (E.g transferrin, ceruloplasmin)
ESTROGEN (contd.)
Effect on bone growth: promotes calcification and bone
growth

 Effect on transhydrogenase: estrogen activates

transhydorgenase.
Reducing equivalents of NADPH + H+ are transferred to NAD+
(catalyzed by transhydrogenase)

After menopause  deficiency of estrogen

transhydrogenase activity low  diversion of NADPH
towards lipogeneis  Obesity
Synthesis of estrogen and
progesterone
Ovarian production of estrogen, progesterone and
androgen requires cytochrome p450 family of oxidative
enzymes.

Ovarian estrogen: C18 steroid with phenolic hydroxyl

group on C3 and either hydroxyl group/ketone group on
C17.

Major steroid producing compartments of ovary:

granulosa cells, theca cells, stromal cells, cells of
corpus luteum.
Synthesis of estradiol in granulosa cells:
Mechanism

Anterior pituitary gland  follicle stimulating

hormone (FSH)  stimulates granulosa cells 
along with catalytic activity of p450 aromatose 
testosterone  to estradiol
Progesterone
Synthesized and secreted by CORPUS
LUTEUM and PLACENTA.
Intermediate product during formation of
steroid hormone from cholesterol.
Production of progesterone is controlled by
LH.
Biochemical functions of
progesterone
Required for the implantation of fertilized ovum and
maintenance of pregnancy.

 Promotes glandular tissue in uterus and mammary gland.

 Increases body temperature by 0.5-1.5 0F.

 Exact mechanism is not known.

 Rise in temperature is indication for ovulation.

Metabolism
Site: Liver
Estradiol, estrone to estriol  substrates for hepatic

enzymes
Conjugated form vs Unconjugated form.

Conjugated form: water soluble  comes out of feces,

bile and urine.

 Progestins: liver, ineffective when administered orally.

Major: sodium pregnanediol-20-glucuronide
3 phase of menstrual cycle
Menstrual period: thickening of endometrium lining
1.

begin to shed off, continues from 4 to 6 days

1.Follicular phase: an egg follicle on an ovary gets ready

to release an egg, can be longer or shorter (determines the
length of cycle),

Luteal phase (premenstrual phase): phase starts

1.
on ovulation day, the day the egg is released from the egg
follicle on the ovary.
1.It
can happen any time from Day 7 to Day 22 of a normal
menstrual cycle.
Luteal phase during
menstrual cycle
Begins on Day 14, after ovulation occurs and continues
until Day 1 of your next period.

Estrogen and progesterone increase  work together to

create changes in the lining of the uterus  prepare it to
accept an embryo  should conception occur.

 When pregnancy does not occur

Estrogen & Progesterone level declines  endometrial lining
sheds off  leads to menstrual cycle
Hormonal and physiological changes
during menstrual cycle
Gonadal function
 Testes cells  testosterone
Regulatedby: Pituitary LH.
Responsible for secondary sexual characteristics.

 Estradiol  main product of ovary

Responsible for secondary sexual characteristics.
Development of ovarian follicle & proliferation of uterine
endothelium.

Hypogonadism in male: Primary & Secondary

Primary: failure of testosterone or spermatogenesis.
Secondary: problem in hypothalamus/ pituitary
Gonad dysfunction in women
Primary amenorrhoea
Secondary amenorrhoea
 Difference between Oligomenorrhoea
and Amenorrhoea

Amenorrhoea Oligomenorrhoea

Complete absence of menstruation Intermittent

(4 to 9 times/year)

Congenital (absence of uterus), Result of prolactinomas (adenomas

developmental problem of anterior pituitary gland)
Biochemical test for infertility
 Failure to conceive even after a year of unprotected
intercourse.

 Data to be taken for examination:

Birthcontrol pills taken, congenital disease,
chemotherapy/radiotherapy, STD, smoking habit, drug habit,
contraceptive practice.
Physical examination in female: Cushing syndrome,
Galactorrhoea, and Hirsutism
Cushing syndrome
Biochemical test for infertility
 In male:
Sperm analysis details: sperm count, sperm volume, sperm
density, motility, and abnormal spermatozoa.

 In female:
Endocrine abnormality: in 1/3rd. Of patients

 In male:
Endocrine abnormality: Rare
NOTE: In some couple abnormalities might not be
observed.
Endocrine investigations in sub-
fertile women
Investigation depends on phase of menstrual
cycle.
If irregularities are observed,
Check for serum progesterone (In middle of
luteal phase (Day 21))
If level of progesterone >30 nmol/L  patient has
ovulated.
If level of progesterone <10 nmol/L  ovulation
has not occurred.
In women: condition of no menstruation
(oligomenorrhoea/ amenohhhoea)  not ovulating
 hormone measurement may be diagnostic.
Subfertility in women because of
endocrine function

Insulin resistance: excess androgen synthesis.

1.

Primary ovarian failure: because of elevation in

1.

gonadotropins and low estradiol concentration (Post-

menopausal pattern)
1.Hormone replacement therapy  assist libido, prevents
osteoporesis, but does not restore fertility.

Hyperprolactinemia: condition of amenorrhoea and

1.

galactorrhoea in women.
1.In male: No early sign of symptoms shows.
Investigation of male
infertility
Investigation of female infertility in
patients with normal menstrual
cycle
Investigation of oligomenorrhoea and
amenorrhea
Investigation of oligomenorrhoea and
amenorrhea
Biochemical, metabolic and
endocrine changes in PCOS
Contraceptives
Synthetic agonist and antagonist
Prevent conception and tumor growth
ESTROGENS
Have estrogenic activity & pharmacological
features
Modifications done to decrease hepatic
metabolism – so that can be given orally
First development: diethylstilbestrol
Others: 17a-ethinyl estradiol, mestranol: oral
contraceptives
Antagonist
Competes with estradiol for intracellular
receptor

Clomiphene competes with estradiol  GnRH

release not retrained  increase amount of LH
and FSH multiple follicle mature
simultaneously  multiple pregnancies can
ensue.
Antagonist
Nafoxidine and tamoxifen combine with
estrogen receptor  forms stable complex with
chromatin  receptor can’t recycle  inhibit
action of estradiol for prolonged period.
Progestins
Difficultto synthesize compound with progestin
activity with no androgenic activity
Example: norethindrone,
medroxyprogesterone (Provera)
Inhibit ovulation for several months
Inhibit cell growth  against endometrial
carcinoma.
Pathophysiology of male
reproductive system
Hypogonadism: lack of testosterone synthesis
Primary hypogonadism: affect testes, causes
testicular failure.
Secondary hypogonadims: defect in
secretion of gonadotropin.
5 different genetic defect in testosterone
synthesis
Example: 5a-reductase deficiency
Pathophysiology of female
reproductive system
Primary hypergonadism: directly involve
ovaries  cause ovarian deficiencies
(decreased ovulation, decreased hormonal
production)
Secondary hypergonadism: loss of pituitary
gonadotropin function
Gonadal dysgenesis (Turner’s syndrome)
 Polycystic Ovarian Syndrome (PCOS):
hirsutism, obesity, irregular menses, imparied
infertility
Normal hormonal values for men

Testosterone 300 - 1100 ng/dl

Prolactin 7 - 18 ng/ml

Luteinising Hormone ( LH) 2 - 18 mIU/ml

Follicle Stimulating Hormone ( FSH): 2 - 18

mIU/ml

Estradiol ( Day 3): < 50 pg/ml

Normal values for women

Follicle Stimulating Hormone (FSH) < 10 mIU/ml >

15 mIU/ml

Luteinising Hormone (LH) < 7 mIU/ml > 15 mIU/ml

-

Prolactin < 25 ng/ml

Thyroid Stimulating Hormone 0.4 - 3.8 uIU/ml

(TSH)
Phase of Cycle
Hormone Follicular Day of LH Surge Mid-luteal
Estradiol ( E2) < 50 pg/ml ( Day 3) > 100 pg/ml
Progesterone < 1.5 ng/ml > 15 ng/ml

The Day 3 estradiol level should be less than 50 pg/ml. A high Day 3
estradiol level suggests poor ovarian reserve.

A mature follicles produces more than 200-300 pg/ml of estradiol

The progesterone level should be more than 15 ng/ml about 7 days after
ovulation. This suggests that the corpus luteum is functioning normally.