insulin & sex hormone

1. Insulin & Sex Hormones
Presented by : Rushikesh S Tidake
M.Pharm II sem
Pharmacology
RSCP Buldana

2. Insulin
• Is a polypeptide hormones produce by ß-cells of
Langerhans of pancreas .
• It has profound influence on metabolism of
Carbohydrates ,fat & proteins.
• It is considered as anabolic hormone

3. • It was the first hormone to be isolated purified &
synthesized
• First hormone to be sequenced
• First hormone to be produced by recombinant DNA
technology

4. Structure
• Human Insulin contain 51 amino acids arranged in two
Polypeptide chains
• Chain A = 21AA
• Chain B = 30AA
• Two interchain Disulfide bridge = A7-B7 & A20-B19
• Intrachain Disulfide link in chain A = 6-11

6. Synthesis
• Gene for protein synthesis is located on Chr 11
• Produced from ß-cells of Langerhans of pancreas
• Synthesis involve two precursor
-Preproinsulin = 108AA
-Proinsulin = 86AA

7. • These are sequentially degraded to form the active hormone
Insulin and Connecting peptide (C-peptide)
• C-peptide has no biological activity,however its estimation in
plasma serves as the useful index for endogenous
production of insulin.
• In ß –cells , Insulin combines with zinc to form a complex &
stored in granules.

8. Transport , fate and excretion :
Insulin circulates in plasma partly in a protein bound
form and partly free form .
It is taken up mostly by liver kidney and skeletal muscle .
No insulin is taken up by red blood cells and brain.
It is degraded by tissues like liver , kidneys testes and
placenta.
It is metabolised by glutathione – insulin
transhydrogenase (insulinase).
This enzymes separates the two chains.
This individual chains are degraded by proteolytic
enzymes

9. Actions of insulin :
A) Liver : In the liver , insulin increases the activity of two enzymes :
1. Glucokinase which increases glucose uptake .
2. Glycogen synthetase which increases glycogen depositon .
 It decreases the activity of other two enzymes :
1. Phosphorylase and CAMP , inhibition of which decreases glycogenolysis
2. Enzymes concerned with glyconeogenesis ( fresh synthesis of glucose from non
– carbohydrate sources
As a result ,the breakdown of liver glycogen and fresh synthesis of glucose is
decreased . But glucose is mobilised to the liver and deposited as glycogen.

10. B. Adipose tissue :
• insulin increases the permeability , uptake and utilization of glucose in the fat cell .
• Increased glucose utilization leads to the synthesis of glycerol , α glycerophosphate
and fatty acids .
•The later two compounds combine to form triglyceraids .
•Thus insulin induces lipogenesis but it prevents lipolysis
C. Skeletal muscle :
•Insulin stimulate the uptake of glucose by the muscle cell .
•It stimulates the entry of amino acids into the cells and its incorporation into
proteins (anabolic effect)
•But it prevents breakdown of fat in muscle (antilpolytic effect)

11. Classsification of Preparation of Insulin :
A.)
Short Acting Plain insulin
Insulin zinc Suspension ( humulin)
Intermediate Insulin
Globin zinc insulin
Isophane Insulin
Long Acting
Protiamine zinc Insulin
Ultralente

12. B. Newer insulin :
1. Nuso : It is bovine insulin in clear , neutral solution
2. Actrapid : It is a clear , neutral solution of monocompetent porcine insulin
3. Rapitard : It is a cloudy mixture of actracid and bovine insulin
4. Monotard : It contains highly purified porcine insulin . It is antigenic.
5. Human Insulin : They are obtained by recombinant DNA technology from E.coli or
yeast .They are widely used at present.
Advantages :
1. More water Soluble
2. Rapid S.C absorption
3. Useful in insulin resistance
4. Useful in allergy to commercial isolations
5. Useful for short term use in surgery or infection

13. Oral Antidiabetic Drugs
Insulin is ineffective orally and so it has to be injected . But the oral antidaibetic drugs lower
blood glucose level on oral administration.
Classification of drugs
1. Sulfonylureas
a) First generation
Tolbutamide
Chlorpropamide
b) Second generation Glibenclamide
Glipizide
Glyclazide
Glymepridie
2. Bigunaides
Metformin

14. Sulfonylureas
MOA:
1. Stimulation of the synthesis and release of insulin from β cells of islets of langerhans
2. Increase the number of beta cells
3. Inhibition of glygenolysis and glyconeogenesis
4. Decrease the rate of insulin degradation .
 Absorption , fate and excretion:
• Sulfonylureas are rapidly absorbed from GIT.
• They are partly bound to plasma proteins.
• They are metabolised in liver and excreted in urine.

15. Biguanides:
MOA
1. The presence of exogenous or endogenous insulin is necessary for action of
biguanides, but insulin release from pancreas is not stimulated
2. Peripheral utilization of glucose is stimulated
3. Absorption of glucose from intestine is inhibited .
 Absorption, fate and excretion:
• These are well absorbed from GIT.
• Maximum activity occures in 4 Hrs.
• They are eliminated through urine within 24 Hrs

16. Sex hormones :
 Sex Hormones belongs to steroid class of compound and
are produced in gonads. i.e testes in male and ovaries in
female .
Their activity is controlled and monitored by the anterior
lobe of pituitary glands.
 Perhaps because of this inherent characteristics the sex
hormones are invariably termed as secondary sex hormones
and the hormones of anterior lobes of pituitary glands are
called as primary sex hormones.

17. Classification
(i)Androgens : testosterone
(ii)Estrogens : Estrone , Estradiol
(iii)Gestogens : Progesterone

18. Testosterone
Mode of action : Androgen binds to
the specific nuclear receptor in target
cell. Although the testosterone itself
is the active ligand in muscle and
liver , in other tissues it must be
metabolized to the derivatives such
as DHT e.g. After diffusing into the
cells of the prostrate , seminal
vesicles , epidermis and skin ,
testosterone is converted by 5α-
reductase to DHT , which binds to
the receptor .

19. Actions:
1. Sex organs and secondary sex characters : Testosterone is responsible
for the all changes that occurs in boy during puberty.
Growth of genitals , growth of hairs , larynx grows and voice deepens .
2. Testes : moderately large doses cause testicular atrophy by inhibiting Gn
secretion from pituitary . Still larger doses have direct sustaining effect
and atrophy is less marked .
3. Skeleton and skeletal muscles ( Anabolics ) : Testosterone is responsible
for pubertal spurt of growth in boys and to a smaller extent in girls .
There is rapid bone growth, both in thickness as well as length . After
puberty the epiphysis fuse and linear growth comes to halt.

20. Uses :
1. Testicular failure : It may be primary – in children , resulting in delayed
puberty . Secondary testicular failure occur mainly as loss of libido ,
muscle mass , feminisation , impotency . These are corrected gradually
over months.
2. Hypopituitarism : Hypogonadism is one of the feature of hypopituitarism.
3. AIDS related muscle wasting : Testosterone therapy has been shown to
improve weakness and muscle wasting in AIDS patient with low
testosterone level .
4. Hereditary angioneurotic edema : This is a genetic disorder . The attack
can be prevented by 17 α alkylated androgens but not by testosterone .
5. Ageing : Because testosterone level decline in old age , it has been
administered to elderly mails to improve bone mineralisation and muscle
mass.

21. Estrogen (Female Sex hormones )
Mechanism of Action
•Genomic Actions : Binds to specific receptors ( er )
Conformational changes ( receptor dimerization leading to
interaction with estrogen response Element , ERE , of target genes )
regulates the protein synthesis.
•Nongenomic Actions :
-Ers located on the cell membrane

22. Actions :
1. Sex organs : The estrogens bring about pubertal changes in
the female including of uterus , fallopian tubes and vagina .
Vaginal epithelium gets thickened , stratified and cornified .
2. Secondary sex characters : Estrogen produce at puberty cause
growth of breasts –proliferation of ducts & stroma,
accumulation of fats.The pubic and axillary hair appear,
feminine body contours and behaviour are influenced.
3. Metabolic effects : Estrogen are anabolic , similar to but weaker
than testosterone . Therefore small amount of estrogen may be
contributing to the pubertal growth spurt even in boys.

23. Uses :
1.)Primary Hypogonadism :
•In estrogen deficinet patients
• Treartment usually begins at 11 -13 yrs of age
•To mimic the physiology of puberty
•Start with small dose of estrogen on days 1-21 each month and increase to adult doses untill
menopause
•Preogestin therapy simulataneously
2.) Hormone replacement therapy :
•Highly efficacious in suppresing the peri- menopausal syndromes
•Dose of estrogen used is less
Conjugated estrogens is 0.625mg/day
•Progestin should be added for 10-12days each month.
•Recent findings emphasis a number of risks and limitations

24. Progesterone
Mode of action :
The progesterone receptors has limited distributio in the
body confined mainly to the feamle genital tract , breast ,
CNS , pituitary .
Upon Hormone binding PR undergoes dimerization ,
attaches progesterone response element (PRE) of target
genes and regulates transcription through co-activators

25. Actions :
1. Uterus : Progesterone brings about secretory changes in the estrogen
primed endometrium : hyperemia , tortuocity of glands and increased
secretion occurs while epithelial proliferatiom is halted it is lack of
progestinal support which causes mucosal shading during menstruation .
2. Cervix : Progesterone converts the watery cervical secretion induced by
estrogens to viscid sacnty and cellular secretion which is hostile to sperm
pentration .
3. Vagina : Progesterone induces pregnancy like changes in the vaginal
mucosa : leucocyte infiltation of cornified epithelium occurs
4. Breast : Progesterone causes proliferation of acini in the mammary glands
5. CNS : High circulating concentration of progesterone appears to have
seadtive effect.It can also affect mood

26. Uses :
1.) As contraceptive : Most common use.
2.)Hormone Replacement Therapy : Used in the nonhysterectomised
post menopausal woman estrogen therapy is supplemented with a
progestin for 10-12 days each month to reduce risk of endometrial
carcinoma .
3.) Dysfunctional Uterine bleeding : Progestin enlarge those promptly
stops the bleeding and keeps it abeyance as long as therapy is given .
Cyclic treatment regularises and normalises menstrual flow.
4.) Endometrial Carcinoma : Progestin are palliative in about 50%
cases of advanced or metastatic endometrial carcinoma .High doses
are needed.

27. Thank you