This document discusses various therapeutic hormones including insulin, growth hormone, gonadotrophins, thyroid stimulating hormone, parathyroid hormone, and calcitonin. It provides details on their structure, function, production, formulations, and medical applications. Key points include: insulin is produced in the pancreas and regulates blood glucose; growth hormone stimulates growth; gonadotrophins like FSH and LH regulate reproduction; recombinant DNA technology is now used to produce many therapeutic hormones which has improved safety over extracts from animal tissues. These hormones are administered to treat various endocrine disorders and fertility issues.

1. Therapeutic Hormones

2. Introduction
Harmones
•Most Important group among regulatory
molecules produce by the body.
•Synthesized and released from a specific glands.
•Interacting with a receptor present in/on a
distant sensitive cell brought about a change in
that target cell.
•Hormones travel to the target cell via the
circulatory system.

3. Hormone to be any regulatory substance that
carries a signal to generate some alteration at a
cellular level.
Under such a broad definition all cytokines for
example could be considered hormones.

4. Examples
• Insulin
• Glucagon
• Somatotrophins
• Gonadotrophins
• Adrenaline

5. Insulin
•Insulin is a polypeptide hormone
• Produced by the beta cells of the pancreatic
islets of Langerhans.
•It plays a central role in regulating blood
glucose levels.
.

7. Other examples
• Glucagon maintain blood glucose level.
• Somatotrophin stimulates growth.
• Gonadotrophins control secondary sexual
characters

8. Therapeutic Hormones
• Hormones administered as drug.
• Synthesize in lab /industries.
• Nowaday genetic manipulation techniques are
used to generate therapeutic hormones.
• E.g. rHGH, rInsulin

9. Insulin
• Insulin is a polypeptide hormone
• Produced by the beta cells of the pancreatic islets of
Langerhans.
• Islets of Langerhans: Known as the insulin-producing
tissue

10. • It stimulates glucose transport
• It stimulates intracellular biosynthetic
pathways
• It inhibits catabolic pathways, such as
glycogenolysis

11. Diabetes mellitus
• Failure of the body to synthesize sufficient insulin
results in the development of insulin-dependent
diabetes mellitus (IDDM).
• Also known as type-1 diabetes.
• IDDM is caused by T-cell-mediated autoimmune
destruction of the insulin-producing β-pancreatic
islet cells in genetically predisposed individuals.

12. • genetic predisposition sometimes also
called genetic susceptibility.
Dosage of insulin:
1. Rapid-acting insulin
2. Short-acting insulin
3. Intermediate-acting insulin
4. Long-acting insulin

13. The insulin molecule
• First identified as an anti-diabetic factor in 1921
• Its complete amino acid sequence was determined in
1951.
• The insulin receptor is a tetrameric integral
membrane glycoprotein consisting of two 735 amino
acid α-chains and two 620 amino acid β-chains.
• These are held together by disulfide linkages.

14. Insulin Production

15. Traditionally insulin preparations
• Animal insulin was the first type of insulin to
control diabetes.
• Until the 1980s, animal insulin was the only
treatment for insulin dependent diabetes.
• Animal insulin is derived from cows and pigs.
• Direct extraction from pancreatic tissue of
slaughterhouse pigs and cattle.

16. Disadvantages
• Slight structural difference of 1-3 amino acids
between the animal insulin and human insulin.
• Diabetic patient developed antibodies against the
animal insulin thereby causing allergic reactions.
• large number of animals were to be sacrificed for
extracting the insulin from their pancreas.
• For example: To obtain 5 kgs. Of pancreatic juice
about 75 pigs have to be killed to get insulin for
treating only a single diabetic patient just for one
year.

17. By recombinant DNA technology
• First approved for general medical use in
1982.
• First product approved for therapeutic use in
humans.
• Insulin consist of two polypeptide chains A
and B.
• inserting the A and B chains into two different
E. coli cells.
• Chain A and B separately synthesized.

18. • The A- and B-chains are then incubated under
required parameters.
• Bond formation.

20. Formulation of insulin

21. • Insulin are formulating in number of way to
alert the order of pharmacokinetic profile
• There are two types pharmacokinetic profiling
• Fast (short)-acting insulins
• Slow-acting insulins

22. • In healthy individuals In healthy individuals, insulin is
typically secreted continuously into the bloodstream at
low basal level
• With rapid increases evident in response to elevated
blood sugar levels
• low-acting insulin preparation, however, accurately
reproduces
normal serum insulin baseline level
• fast-acting insulin will not produce
• a plasma hormone peak for 1.5–2 h post injection, and
levels then remain elevated for up to 5 h.

23. Prolong the duration of insulin action
• This is generally achieved in one of two
ways:
• Addition of zinc in order to promote Zn–
insulin crystal growth
• Addition of a protein to which the insulin will
complex
• The proteins normally used are
protamine's

24. Engineered insulins
• Recombinant DNA technology facilitates not only production
of human insulin in microbial systems, but also facilitates
generation of insulins of modified amino acid sequences
• The major aims of generating such engineered insulin
analogues include:
• Identification of insulins with altered pharmacokinetic
properties
• Identification of super-potent insulin forms
• The insulin amino acid residues that interact with the insulin
receptor have been identifi ed (A1,
• A5, A19, A21, B10, B16, B23-25), and a number of analogues
containing amino acid substitutions at several of these points
have been manufactured.

25. Modified insulins
• modified insulins have now been approved for medical
injected at mealtimes rather than1 h before
• Several Engineered insulins are inliste
• Insulin lispro’ (tradename ‘Humalog’) was the first
such engineered short-acting insulin to come to
market
• ‘Insulin Aspart’ is a second fast-acting engineered
human insulin
• It differs from native human insulin in that the prolineB28
residue has been replaced by aspartic acid
• This single amino acid substitution

26. • Optisulin or Lantus are the tradenames given to one such
analogue that gained general marketing approval in 2000
• It differs from native human insulin in that the C-terminal
aspargine
residue of the A-chain has been replaced by a glycine residue
and the β -chain has been elongated(again from its C-terminus)
by two arginine residues
• Levemir (tradename) is an alternative engineered long-
acting insulin product that gained approval for general medical
use in 2004
• This differs from native insulin in that it is devoid of the
threonine B30 residue and (more importantly from a
pharmacokinetic perspective)contains a 14-carbon fatty acid
residue covalently attached to the side chain of lysine residue
B29

27. Glucagon

28. Glucagon
• Polypeptide
• Single chain (29 amino acids)
• Its function is contradictory to insulin.
• Secretes in response to hypoglycemia.
• Promotes catabolic activity.
i.e.
• Break down of stored energy
• stimulates gluconeogenesis.

29. Glucagon
• Source: Pancreas
• Extract from bovine & porcine pancreatic
tissues.
• Used as freeze dried hormone.
• Dosage routes : Subcutaneous &
Intramuscular
• Now Recombinant products are available.
• E.g . Glucagen

31. Human Growth Hormone
• Somatotrophin.
• Hormone : Stimulates growth
• 191 amino acid
• Released by pituitary glands.
• Traditionally extracted from bovine /porcine
source.

32. Therapeutic Uses
• Wide range of applications
• Treatment of dwarfism (1958).
• Stimulation of lactation.
• rhGH was produce in 1980 .
• rhGH was first purified (on a laboratory scale)
by Genentech

33. Gonadotrophins
• Group
• Produced
Proteins Hormones
Gonadotropes cell
Pituitary
glands

34. They directly and indirectly regulate ;
• Reproductive function
• secondary sexual characteristics

35. Hypothalamus
Pituitary glands
GnRH
FSH LH

36. Types
FSH LH HCG

37. Follicle stimulating Hormone
Females
• Helps ovarian follicle to
develop.
• Promotes estrogen
secretion.
Males
• Promotes sperm
development

38. luteinizing hormone
Females
• Stimulation ovulation
• Promotes secretion of
estrogen and
progesterone
Males
• Stimulates production
of testosterone

39. Human Chorionic Hormones
• It is a hormones produced naturally by the
pregnant women to ensure the correct
nourishment of the baby

40. Medical Applications of
Gonadotrophin Hormones

41. • The therapeutic potential of gonadotrophins in
treating subfertility/some forms of infertility.
• Gonadotrophins are also used to induce a
superovulatory response in various animal specie.
• The human pituitary is the obvious source of
human gonadotrophins.
• The urine of post-menopausal women does
contain both FSH and LH activity.

42. • Menotrophin (human menopausal
gonadotrophin) is the name given to FSH-
enriched extracts from human urine.
• Such preparations contain variable levels of LH
activity, as well as various other proteins normally
present in urine.
• hCG exhibits similar biological activities to hLH
and is excreted in the urine of pregnant women

44. Applications:
• Treatment of anovulatory infertility.
• Treatment of females with blocked fallopian
tube.
• Treatment of male subfertility or related
conditions.
• Future additional clinical applications.

45. 1. Treatment of anovulatory infertility.
• In females, menotrophins and hCG are used
for the treatment of infertility.
• Menotrophin is administered to stimulate
follicular maturation, along with hCG to
promote ovulation and corpus luteum
formation.

46. Dosage:
• Gonadotrophin, often given for 12 days or
more, followed by a single dose of hCG.
• Three equal larger doses of menotrophin are
given on alternate days.
• Followed by hCG administration 1–2 days.

47. Dosage Level:
• Dosage of both hormones is given same as the
amount of them produced normally during
the reproductive cycle of fertile females.
• Depending upon the basal hormonal status of
the female, calculation of the optimal dosage
levels can be tricky.
• Overdosage can result in risk of multiple
pregnancy.

48. 2. Treatment of Female Infertility:
• FSH given in more quantity than normal to allow
the female to stimulate multiple follicular growth.
• Often employed when a woman has a blocked
fallopian tube.
• After treatment, the resultant eggs are
collected, incubated in vitro with partner’s
sperm.
• Cultured and incubated untill blastocyts formed
and implanted back.

49. 3. Treatment of Male Subfertility:
• FSH and hCG are also involved in treatment of
male infertility.
• Given to males having hypogonadotrophic
hypogonadism (HH) to stimulate sperm
synthesis.
• hCG has also application in the treatment of
cryptorchidism condition.

50. 4. Clinical Applications:
• Cell surface receptor of LH & hGC is found in a
number of non-gonadal tissue.
• These hormones may possess other than
reproductive functions.
• It is expressed by a number of tissues before
birth, hinting at a potential developmental
role.
• Receptor levels in non-gonadal tissues are
generally much lower than in gonadal tissue.

51. Recombinant gonadotrophins
 Recombinant DNA technology
 rhFSH produced in CHO cells has proven
clinically effective
 When administered to humans, the
preparation is well tolerated and yields no
unexpected side effects
 hypogonadotrophic hypogonadism

52. Recombinant gonadotrophins now
approved for general medical use in
the EU and USA
Product Company Indication
Gonal F (rhFSH) Serono Anovulation and
Superovulation Puregon (rhFSH) N.V. Organon
Anovulation and Superovulation Follistim (rhFSH)
Organon Some forms of infertility
Luveris (rhLH) Ares-Serono Some forms of
infertility
Ovitrelle (rhCG) Serono Selected assisted
reproductive techn

53. Ovitrelle
 Ovitrelle (tradename in EU, sold as Ovidrel in
the USA and also known as
choriogonadotropin alfa) is a recombinant
hCG
Treatment of female infertility due to
anovulation
 It is used to trigger final follicle maturation
and luteinization after follicle stimulation.

54. Veterinary uses of gonadotrophins
 Treat subfertility in animals
 Horses and cattle
 FSH is administered to the animal such that multiple
follicles develop simultaneously
 After administration of LH to help promote ovulation,
the animal is mated, thus fertilizing the released egg
cells
 Embryos are recovered and maintained in cell culture
for a short period of time.
 Single embryo is then usually reimplanted into the
donor female, while the remaining embryos are
implanted into the surrogate mothers

55. e.g. prize winning horses, or high milk-yield
dairy cattle to boost their effective reproductive
capacity

56. Porcine FSH (p-FSH) and Porcine LH
(p-LH)
 p-FSH is extracted from the pituitary glands of
slaughterhouse pigs. The crude pituitary extract is
usually subject to a precipitation step, using either
ethanol or salts.
 The FSH-containing precipitate is normally subjected
to at least one subsequent chromatographic step.
 p-LH is obtained, again, by its partial purification from
the pituitary glands of slaughterhouse pigs.
 The final product often contains some LH and low
levels of additional pituitary derived proteins
 Target recipients are cattle or horses

57. Additional recombinant
hormones now approved
• Three additional recombinant
hormones have recently gained
marketing approval:
• Thyroid-stimulating hormone
• Parathyroid hormone
• Calcitonin.

58. Thyroid stimulating harmone
• Structurally, thyroid-stimulating hormone (TSH or
thyrotrophin) is classified as a member of the
gonadotrophin family, although functionally it
targets the thyroid gland as opposed to the
gonads.
• TSH is synthesized by a distinct pituitary cell type:
the thyrotroph. Its synthesis and release are
promoted by thyrotrophin-releasing hormone.
• TSH exerts its characteristic effects by binding
specific receptors found primarily, but not
exclusively, on the surface of thyroid gland cells.

59. Human parathyroid hormone
• Human parathyroid hormone (hPTH) is an 84
amino acid polypeptide that functions as a
primary regulator of calcium and phosphate
metabolism in bones. It stimulates bone
formation by osteoblasts, which display high-
affinity cell surface receptors for the hormone.
• PTH also increases intestinal absorption of
calcium.

60. Calcitonin
• Calcitonin is a polypeptide hormone that plays
a central role in regulating serum ionized
calcium (Ca2) and inorganic phosphate (Pi)
levels.
• The adult human body contains up to 2 kg of
calcium, of which 98 per cent is present in the
skeleton (i.e. bone). Up to 85 percent of the 1
kg of phosphorus present in the body is also
found in the skeleton.

61. • Calcitonin lowers serum Ca2 and Pi levels,
primarily by inhibiting the process of bone
resorption, but also by decreasing resorption
of Pi and Ca2 in the kidney.
• Calcitonin receptors are predictably found
primarily on bone cells (osteoclasts) and renal
cells.

62. • Calcitonin is used clinically to treat
hypercalcaemia associated with some forms of
malignancy and Paget’s disease. The latter
condition is a chronic disorder of the skeleton
in which bone grows abnormally in some
regions.

63. Conclusion
• Several hormone preparations have a long history of use as
therapeutic agents.
• Usually these are administered when the patients are not
producing enough quantities of endogenous hormones.
• Insulin has saved or prolonged the lives of millions of
diabetic patients.
• Gonadotrophins have allowed thousands of sub-fertile
individuals to conceive.
• GH has improved the quality of life of thousands of people
of short stature.
• Recombinant hormonal preparations, however, are now
gaining greater favour, mainly on safety grounds.

64. Questions ?
If any. Feel free to ask!