Endocrine pharmacology in Brief

Pharmacology of Endocrine system in brief

1. Pharmacology of the Pharmacology of the
Endocrine SystemEndocrine System

2. TopicsTopics
Pituitary and hypothalamic hormonesPituitary and hypothalamic hormones
Thyroid and antithyroid DrugsThyroid and antithyroid Drugs
Adrenal DrugsAdrenal Drugs
Pancreatic DrugsPancreatic Drugs
Gonadal hormones and inhibitorsGonadal hormones and inhibitors

3. TheThe Endocrine System Endocrine System
Controls many body functionsControls many body functions
–exerts control by releasing special chemical exerts control by releasing special chemical
substances into the blood called substances into the blood called hormoneshormones
–Hormones Hormones affect other endocrine glands or affect other endocrine glands or
body systemsbody systems

4. Endocrine System Endocrine System

6. Hormone
 A substance that is releaseA substance that is releasedd in one tissue and in one tissue and
travels through the circulation (usually) to the travels through the circulation (usually) to the
target tissue. target tissue.
Hormones reach all parts of the body, but only Hormones reach all parts of the body, but only
target cells are equipped to respondtarget cells are equipped to respond
Hormones are secreted in small amounts and Hormones are secreted in small amounts and
often in bursts (pulsatile secretion)often in bursts (pulsatile secretion)

7. Endocrine FunctionsEndocrine Functions
• Maintain Internal Homeostasis
• Support Cell Growth
• Coordinate Development
• Coordinate Reproduction , fertility, sexual
function
• Facilitate Responses to External Stimuli

8. 4 Classes of Hormones4 Classes of Hormones
1.1.Peptide/ Protein Peptide/ Protein ((Range from 3 amino Range from 3 amino
acids to hundreds of amino acids in size. )acids to hundreds of amino acids in size. )
2.2.SteroidSteroid
3.3.Amine Amine (Thyroid hormones and (Thyroid hormones and
Catecholamines)Catecholamines)
4.4.Eicosanoid Eicosanoid (Fatty acid derivatives )(Fatty acid derivatives )

9. The hormones fall into two general classes based
on their solubility in water.
The water soluble { amine (epinephrine) and
peptide/protein hormones} are secreted by
exocytosis, travel freely in the bloodstream,
and bind to cell-surface receptors.
The lipid soluble hormones { thyroid hormone,
steroid hormones and Vitamin D3}. diffuse
across cell membranes, travel in the
bloodstream bound to transport proteins, and
diffuse through the membrane of target cells .

10. NUCLEUS
Signal
receptor
(a) (b)
TARGET
CELL
Signal receptor
Transport
protein
Water-
soluble
hormone
Fat-soluble
hormone

11. Location of receptorsLocation of receptors
-On cell surfaceOn cell surface
Peptides and proteinsPeptides and proteins
-In cytoplasmIn cytoplasm
SteroidsSteroids
-In nucleusIn nucleus
Thyroid hormonesThyroid hormones

12. Mechanisms of endocrine diseaseMechanisms of endocrine disease
Endocrine disorders result from:
Hormone deficiency,
(HRT)(HRT)
Hormone excess
(Specific antagonists or release (Specific antagonists or release
inhibitors )inhibitors )
Hormone resistance
(sensitizers(sensitizers)

13. Sources of hormones:Sources of hormones:
-Natural
Human (GH; LH & FSH; hCG);
Animal (Insulin, T
3
& T
4
)
-Biosynthetic
Insulin (Porcine & Bovine)
-Synthetic
Most hormones and their antagonists
DNA recombinant technology

14. Hypothalamic &
Pituitary Hormones

15. Spinal cord
Posterior
pituitary
Cerebellum
Pineal
gland
Anterior
pituitary
Hypothalamus
Pituitary
gland
Hypothalamus
Thalamus
Cerebrum

16. Hypothalamus and Pituitary
The output of the hypothalamus-pituitary unit regulates the
function of the thyroid, adrenal and reproductive glands and
also controls somatic growth, lactation, milk secretion and
water metabolism.
Hypothalamic Hs can have effect of stimulating or inhibiting
the release of ant. Pit. Hs. Called RELEASING HORMONES
“RH” or INHIBITING HORMONES “IH” respectively, reflecting their
influence on ant. Pit. Hs.

17. The Pituitary GlandThe Pituitary Gland
The Pituitary Gland is divided into 2 areas, with separate types
of hormone production.
The anterior pituitary makes and releases H under
regulation of the hypothalamus
Growth Hormone (GH)
Thyroid-stimulating Hormone (TSH)
Adrenocorticotropin (ACTH)
Follicle-stimulating Hormone (FSH) ),
Leutinizing Hormone (LH),
Prolactin
–The posterior pituitary stores and secretes H that are
made in the hypothalamus: oxytocin and antidiuretic
hormone (ADH)

19. HypothalumusHypothalumus Ant. pituitaryAnt. pituitary Post. PituitaryPost. Pituitary
Growth hormone-releasing Growth hormone-releasing
hormone(GHRH) hormone(GHRH) ++
Growth Hormone (GH), Growth Hormone (GH),
Antidiuretic Hormone Antidiuretic Hormone 
Growth hormone-releasing Growth hormone-releasing
inhibiting hormone inhibiting hormone
(GHRIH)_(GHRIH)_
SomatostatinSomatostatin
Thyrotropin-releasing Thyrotropin-releasing
hormone (TRH)+hormone (TRH)+
Thyroid Stimulating Thyroid Stimulating
Hormone (TSH), Hormone (TSH), OxytocinOxytocin
Corticotropin-releasing Corticotropin-releasing
hormone (CRH)+hormone (CRH)+
Adrenocorticotropic Adrenocorticotropic
Hormone (ACTH), Hormone (ACTH),
Gonadotropin-releasing Gonadotropin-releasing
hormone (GnRH)+ hormone (GnRH)+
Follicle-stimulatingFollicle-stimulating
Hormone (FSH), Hormone (FSH),
Luteinizing Hormone(LH).Luteinizing Hormone(LH).
Dopamine _Dopamine _ Prolactin,Prolactin,

20. Hypothalamic hormones:Hypothalamic hormones:
1- Growth Hormone- Releasing Hormone(GHRH):1- Growth Hormone- Releasing Hormone(GHRH):
Together with somatostatin controls release of the GH from the Together with somatostatin controls release of the GH from the
ant. pit. ant. pit.
It is released from hypothalamus in a pulsatile
fashion, with 5-9 major pulses detected per day.
• GHRH release is enhanced by α2-adrenergic agonists
(e.g. clonidine) and opioids.
• GHRH release is increased by vigorous exercise.

21. Diagnostic Uses of GHRH (Sermorelin)Diagnostic Uses of GHRH (Sermorelin)
To test pituitary function in patients with GH To test pituitary function in patients with GH
deficiency.deficiency.

GH deficiency could reflect either a hypothalamic or a pit. defect.GH deficiency could reflect either a hypothalamic or a pit. defect.
If the primary defect is hypothalamic, as is most common, If the primary defect is hypothalamic, as is most common,
GHRH will elicit an increase in GH release. GHRH will elicit an increase in GH release.
If the defect is at the level of the pituitary, there will be no If the defect is at the level of the pituitary, there will be no
increase in GH following GHRH administration.increase in GH following GHRH administration.
Therapeutic Uses of GHRH to enhance GH secretionTherapeutic Uses of GHRH to enhance GH secretion

Pulsatile subcutaneous delivery of GHRH,
mimicking the normal endogenous patterns (e.g. ~
every 3 hours) has been used to stimulate GH
release in patients with GH deficiency that is not of
pituitary origin.
IV, SC, intranasalIV, SC, intranasal

22. Inhibits GH release and TSH from the ant. pituitary .
Inhibits release of most GI hormones, reduces gastric acids and pancreatic
secretion. (glucagon , insulin & gastrin),
Therapeutic Uses Somatostatin Therapeutic Uses Somatostatin
Somatostatin is of no clinical value because of it's short half-life (<3 min)
Octreotide ,a synthetic somatostatin analogue with a longer duration of action

Lanreotide is much longer acting, and is administered only twice a month.
 used to treat: Acromegaly, Gastrinoma ,Glucagonoma & Other Endocrine
Tumors , and esophageal varices bleeding. (Inhibits Mesenteric vasodilatation induced by
glucagon)
A/E: GI disturb. postprandial hyperglycemia.
Gall stones often form as a result of decreased biliary flow and gall bladder
contraction.
2- 2- Somatostatin (Growth hormone-releasing Somatostatin (Growth hormone-releasing
inhibiting hormone (GHRIH):inhibiting hormone (GHRIH):

23. 3- Thyrotropin-Releasing Hormone(TRH):3- Thyrotropin-Releasing Hormone(TRH):
Stimulates release of thyrotropin (TSH) from the ant pit.
Is used in diagnostic testing of thyroid dysfunction
Protirelin: IV
4- Corticotropin Releasing 4- Corticotropin Releasing
Hormone(CRH) Hormone(CRH)
It It stimulates secretion of both ACTH & beta –endorphin (a
closely related peptide ) from the ant. pituitary .
CRH can be used in the diagnoses of abnormalities of ACTH
secretion .

24. 5- Gonadotropin-Releasing Hormone:(GnRH):5- Gonadotropin-Releasing Hormone:(GnRH):
Stimulate the gonadotroph cell to produce and release Stimulate the gonadotroph cell to produce and release LH LH
and and FSHFSH,,
Gonadorelin, Buserelin, NafarelinGonadorelin, Buserelin, Nafarelin
GnRH agonists, SC infusion in GnRH agonists, SC infusion in pulsespulses mimic mimic physiological physiological
GnRH, stimulates ovulation.GnRH, stimulates ovulation.
In contrast, In contrast, steadysteady dosing inhibits gonadotropin release by dosing inhibits gonadotropin release by
causing down –regulation (desensitization) of GnRH causing down –regulation (desensitization) of GnRH
receptors in pituitary cells that normally release receptors in pituitary cells that normally release
gonadotropins .gonadotropins .
GnRH is used in the diagnosis & treatment (by pulsatile GnRH is used in the diagnosis & treatment (by pulsatile
administration) of administration) of hypogonadalhypogonadal states in females & males . states in females & males .
Continuous GnRH agonists are used in sex H-dependent Continuous GnRH agonists are used in sex H-dependent
conditions: prostate & breast cancers, uterine fibroids, conditions: prostate & breast cancers, uterine fibroids,
endometriosis or precocious puberty .endometriosis or precocious puberty .

25. 6- Prolactin-Inhibiting Hormone (PIH,dopamine):6- Prolactin-Inhibiting Hormone (PIH,dopamine):
Dopamine is the physiologic inhibitor of prolactin release Dopamine is the physiologic inhibitor of prolactin release
Because of its peripheral effects & the need for parenteral Because of its peripheral effects & the need for parenteral
administration, dopamine is not useful in the control of administration, dopamine is not useful in the control of
hyperprolactinemia, but hyperprolactinemia, but bromocrptine bromocrptine & other orally active & other orally active
ergot –derivatives (egergot –derivatives (eg. Cabergoline. Cabergoline, , pergolinepergoline) are effective ) are effective
in reducing prolactin secretion from the normal glands as in reducing prolactin secretion from the normal glands as
well as from prolactinomas .well as from prolactinomas .
Also used in treatment of acromegalyAlso used in treatment of acromegaly
A/E: orthostatic hypotension, Psychiatric manifestationsA/E: orthostatic hypotension, Psychiatric manifestations

26. Pituitary HormonesPituitary Hormones

27. Anterior pituitary
Hormones

28. Growth HormoneGrowth Hormone
•Derived from the somatotroph cells
•Its secretion is controlled by GHRH and somatostatin;
•GH secretion is high in newborn, deceasing at 4 yr to an
intermediate level, which is then maintained until puberty,
when there is further decline.
•Insulin-like growth factor 1 (IGF-1) released from the liver
inhibits GH secretion by stimulating somatostatin secretion
from the hypothalamus,

29. Growth Hormone ActivityGrowth Hormone Activity
1.Increases plasma free fatty acids (source of energy for
muscle tissue)
2.Increases hepatic glucose output
3.Decreases insulin sensitivity in muscle
4.Is protein anabolic hormone
Growth Hormone DeficiencyGrowth Hormone Deficiency
Can have a genetic basis or can be acquired as a result of
damage to the pituitary or hypothalamus by a tumor,
infection, surgery, or radiation therapy.
In childhood: short stature and adiposity, hypoglycemia.
Adults : generalized obesity, reduced muscle mass.

30. GROWTH HORMONE EXCESSGROWTH HORMONE EXCESS
Mainly benign pituitary tumor
In adults causes acromegaly,
If this occurred before the long bone epiphyses
close, it leads to the rare condition, gigantism.
Treatment of excess GH disorders:
- Synthetic Somatostatin (Octreotide)
- DA agonists (Bromocriptine)
- Surgical removal / Radiotherapy of the tumor
- GH Antagonists (Pegvisomant)

31. An excess of GH can An excess of GH can
cause gigantism, cause gigantism,
while a lack of GH while a lack of GH
can cause dwarfismcan cause dwarfism

32. Clinical uses of GHClinical uses of GH
SomatotropinSomatotropin
GH deficiency in children & adults. GH deficiency in children & adults.
Children with short stature that is due to factors Children with short stature that is due to factors
other than GH deficiency:other than GH deficiency:
Idiopathic short stature, Turner syndrome, Chronic renal Idiopathic short stature, Turner syndrome, Chronic renal
failurefailure
A/EA/E: :
Hypothyroidism, Pancreatitis, Gynecomastia, Hypothyroidism, Pancreatitis, Gynecomastia,
Possibilities of abuse have also arisen, e.g. creation
of “super” sports people.

33. Thyroid-stimulating Hormone (TSH)Thyroid-stimulating Hormone (TSH)
Also called thyrotrophinAlso called thyrotrophin
Stimulates secretion of thyroid hormone &
growth of thyroid gland.
Diagnostic Uses of TSHDiagnostic Uses of TSH
In patients who have been treated In patients who have been treated
surgically for thyroid carcinoma, to test for surgically for thyroid carcinoma, to test for
recurrencerecurrence

34. Adrenocorticotropin (ACTH)Adrenocorticotropin (ACTH)
Stimulates cortisol secretion by the adrenal cortex &
promotes growth of adrenal cortex
Diagnostic useDiagnostic use: as a test of the capacity of the
adrenal cortex to produce cortisol;

35. Follicle Follicle ––stimulating hormone (FSH)stimulating hormone (FSH)
•
Females: stimulates growth & development of ovarian
follicles, promotes secretion of estrogen by ovaries.
•Males: required for sperm production
3 preparations are available for clinical use:
 Urofollitropin ,purified from of the urine of post menopausal
women,
2 recombinant forms, follitropin alpha & follitropin beta.
These products are used in combination with other drugs to
treat infertility in women & men.

36. Leutinizing hormone (LH)Leutinizing hormone (LH)
•Females: responsible for ovulation, formation of corpus luteum
in the ovary, and regulation of ovarian secretion of female sex
hormones.
•Males: stimulates cell in the testes to secrete testosterone
•Lutropin alfa, approved for use in combination with
follitropin alfa for stimulation of follicular development in
infertile women with profound LH deficiency. .

37. ProlactinProlactin
Secreted by lactotroph cells of the ant. Pit., which increase
in number during pregnancy.
Its secretion is stimulated by estrogen
•Females: stimulates breast development and milk
production.
• Males: involved in testicular function
No preparation of prolactin is available for use in prolactin-
deficient patients.
For patients with symptomatic hyperprolactinemia,
inhibition of prolactin secretion can be achieved with
dopamine agonists, which act in the pituitary to inhibit
prolactin release.

38. Posterior pituitary
Hormones

39. OxytocinOxytocin
•It is synthesized in the hypothalamus & transported to It is synthesized in the hypothalamus & transported to
the post. Pit.the post. Pit.
• It is an effective stimulant of It is an effective stimulant of uterine contractions uterine contractions & is & is
used intravenously to induce or reinforce used intravenously to induce or reinforce laborlabor . .
•Induces the Induces the release of milkrelease of milk
•Suckling sends a message to the hypothalamus via Suckling sends a message to the hypothalamus via
the nervous system to release oxytocin, which further the nervous system to release oxytocin, which further
stimulates the milk glandsstimulates the milk glands

40. Clinical uses of oxyticinClinical uses of oxyticin
IV, IMIV, IM
Induction of laborInduction of labor
Control of postpartum bleedingControl of postpartum bleeding
A/EA/E : :
fetal distress, placental abruption, or uterine fetal distress, placental abruption, or uterine
rupturerupture
excessive fluid retention excessive fluid retention

41. Vasopressin (antidiuretic hormone ADH)Vasopressin (antidiuretic hormone ADH)
•It is synthesized in the hypothalamus & transported to the post. It is synthesized in the hypothalamus & transported to the post.
Pit.Pit.
The function of The function of ADHADH is to is to increase water conservation increase water conservation by the by the
kidney. kidney.
 If there is a If there is a highhigh level of ADH secretion, the kidneys level of ADH secretion, the kidneys reabsorbreabsorb
water. water.
If there is a If there is a lowlow level of ADH secretion, the kidneys level of ADH secretion, the kidneys releaserelease
water in water in dilute urinedilute urine..
ADH release increases if blood pressure falls or blood becomes ADH release increases if blood pressure falls or blood becomes
too salty.too salty.
ADH causes peripheral blood vessel constriction to help elevate ADH causes peripheral blood vessel constriction to help elevate
blood pressure .blood pressure .

42. Clinical usesClinical uses
Diabetes insipidus, Diabetes insipidus,
Nocturnal enuresis (by decreasing Nocturnal enuresis (by decreasing
nocturnal urine production)nocturnal urine production)
A/E: hyponatremia and seizures A/E: hyponatremia and seizures
Synthetic ADH drugsSynthetic ADH drugs
– Vasopressin: IV, IMVasopressin: IV, IM
–Desmopressin: IV, IM. PO, intranasalDesmopressin: IV, IM. PO, intranasal