1. PRESENTED BY :
SREYA. S
M. Pharmacy
DEPT OF PHARMACOLOGY
1

2. INTRODUCTION
 Prolactin (PRL), also known as luteotropic
hormone or luteotropin, is a protein best known for its role
in enabling mammals (and birds), usually females,
to produce milk.
 Prolactin is secreted from the pituitary gland in response
to eating, mating, estrogen treatment, ovulation and
nursing.
 It is secreted heavly in pulses in between these events.
Prolactin plays an essential role in metabolism, regulation
of the immune system and pancreatic development.
2

3.  Human PRL is a single-chain
polypeptide of 199 amino acids. It
has a molecular weight of 23 kDa.
 The pituitary gland (also called the
master gland) is an endocrine gland
about the size of a pea (weighing
0.5 g) and located at the base of the
brain (just below the
hypothalamus).
 The pituiary gland has two parts –
the anterior lobe and posterior lobe
– that have two seperate functions.
 The pituitary gland secrets
hormones regulating homeostasis,
including tropic hormones that
stimulate other endocrine glands.
3

4. HISTORY OF PROLACTIN
 Around eighty years ago researchers first established that
the pituitary gland regulates mammary gland function as
demonstrated by the ability of its extract to promote both
mammogenesis and lactogenesis in animal models.
 Prolactin (PRL), contributing to these effects
 Mid 1930s PRL had been purified as a distinct lactogen.
 Interest in these hormones initially centered about their
potential for increasing milk production, while in the latter
half of the twentieth century it became obvious that these
hormones also had the potential to influence mammary
cancer development.
4

5. Regulation of secretion
 Release takes place after
stimulation like; Suckling, sound
of hungry pups
 Prolactin is under tonic inhibitory
control by the hypothalamus
through release of dopamine
 Increased levels of estrogen in
pregnancy induce release of
prolactin
 Suckling overrides dopamine’s
inhibitory control through
neurogenic signals from the
breast.
 Suckling increases prolactin levels
markedly (100 fold increase
within 30 min of breast feeding)
5

6.  In males, the influence of PIH
predominates.
 In females, PRL levels increase and
decrease in accordance with estrogen
blood levels;
 Low estrogen levels stimulate
PIH release.
 High estrogen levels promote
release of PRH and thus PRL.
 Blood levels increase towards the end
of the pregnancy.
 When the mother no longer needs to
produce milk, dopamine inhibits
prolactin by signaling the hypothalamus
to stop.
6

7. Prolactin receptor
 Prolactin receptors are present in
the mammillary glands, ovaries,
pituitary glands, heart,
lung, thymus, spleen, liver,
pancreas, kidney, adrenal
gland, uterus, skeleta muscle, skin and
areas of the central nervous system .
 When prolactin binds to the receptor,
it causes it to dimerize with another
prolactin receptor.
 This results in the activation of Janus
kinase 2, a tyrosine kinase that initiates
the JAK-STAT pathway.
 Activation also results in the
activation of mitogen-activated protein
kinases and Src kinase.
7

8. 8

9. Physiological role
 Prolactin receptor are not only found in the mammary
gland but are widely distributed throughout the body,
including the brain, ovary, heart and lungs.
 Along with estrogens, progesterone and several other
hormones, causes growth and development of breast
during pregnancy.
 It causes proliferation of ductal as well as acinar cells in
the breast and induces synthesis of milk proteins and
lactose.
 After parturition prolactin induce breast milk secretion
 Prolactin suppresses hypothalamic-pituatory gonadal axis
byinhibiting GnRH release
9

10.  Reproductive; inhibition of ovulation by decreasing
secretion of LH and FSH during pregnancy.
 Regulation of immune system;by stimulating T cell
functions.
 Osmoregulation; transporting fluid, Na, Cl and Ca across
epithelial intestinal membrane and promoting Na, K and
water retention in the kidney.
 Metabolism; essential in fat cell production,
differentiation and regulation.
 Prolactin also stimulates proliferation of oligodendrocyte
precursor cells .These cells differentiate
into oligodendrocytes, the cells responsible for the
formation of myelin coatings on axons in the central
nervous system.
10

11. Pathological role
 Hyper prolactinaemia is responsible for the galactorrhoea
amenorrhoea infertility syndrome. In males it causes loss
of libido and depressed fertility.
 Disorders of hypothalamus decreases inhibitory control
over pituitary.
 Antidopaminergic and DA depleting drugs causes hyper
prolactinaemia
 Prolactin secreting tumours-these may be
microprolactinomas or macroprolactinomas.
11

12. Prolactin Inhibitors
a) Bromocriptine: synthetic ergot derivative 2-bromo-
aergocryptine is a potent dopamine agonist weak a
adrenergic blocker .
b) Cabergoline: It is a newer D2 agonist; more potent;
more D2 selective and longer acting (t½> 60 days) than
bromocriptine less side effects than bromocriptine.
12

13. Actions:
 Activating dopaminergic receptors and decreases Prolactin
release.
 In normal individuals increases GH release but decreases
the same from pituitary tumours that cause acromegaly.
 It has levodopa like actions in CNS-antiparkinsonian and
behavioural effects produces nausea and vomiting by
stimulating dopaminergic receptor in CTZ.
 Hypotension due to central suppression of postural
refluxes & weak adrenergic blocker.
 Decreases GI motility.
13

14. Uses:
 In treatment of conditions like;
 Hyperprolactinemia: In women it shows galactorrhoea,
amenorrhoea and infertility & men gynaecomastia,
impotence and sterility. lower doses ( bromocriptine 2.5-
10 mg/ day or cabergoline 0.25-1.0 mg twice weekly) are
effective.
 Acromegaly (Due to small pituitary tumours) : Slightly
higher doses of bromocriptine required (5-20 mg/day) .
 Parkinsonism: Bromocriptine effective only at high
doses (20-80 mg/day)and response is similar to that of
levodopa
 Diabetic mellitus
 Hepatic coma
14

15. Adverse drug reaction:
 Early: Nausea, vomiting, constipation, nasal blockage.
 Postural hypotension in patients taking anti
hypertensives.
 Late: Behavioral alterations, mental confusion,
hallucinations, psychosis and Abnormal movements
15

16. Causes and Symptoms of Hypoprolactinaemia
 Decreased PRL hormone secretion by the anterior
pituitary gland
Common causes of Hypoprolactinaemia:
Sheehan'ssyndrome (caused by ischaemic necrosis of the
pituitary gland due to blood loss during or after child
birth)
 Hypopituitarism , Excess dopamine , Autoimmune
disease , Growth hormone deficiency , Head injury ,
Infection (e.g. Tuberculosis)
Symptoms:
 Ovarian diseases, delayed puberty and infertility,
Impotence and abnormal spermatogenesis.
16

17. Causes and symptoms of Hyperprolactinaemia
 Increased PRL hormone secretion by the anterior piruitary
gland
Common causes of Hyperprolactinaemia
 Stress
 Medications e.g. Antipsychotic drugs
 Primary hypothyroidim: PRL is stimulated by the increase of
TRH.
 Pituitary gland tumours
 Prolactinoma: a non-cancerous tumour of the pituitary cell
secreting PRL.
 Idiopathic hypersecretion: e.g. due to impaired secretion of
dopamine
 Other: chest wall lesions and chronic renal failure.
17

18. Symptoms:
Women:
 Oligomenorrhoea , Amenorrhoea, ,Galactorrhoea ,Infertility
,Hirsutim , Osteoporosis
Men (late onset):
 Gynaecomastia , Impotence ,Osteoporosis
In both sexes,
tumour mass effects may cause visual field defects and
headache
18

19. REFERENCES
• Tripathi K.D. Essentials Of Medical Pharmacology. 7th
ed. Jaypee Brothers Medical Publishers; 2014:[182-191]
• Rang H.P ,Dale M.M, Ritter J.M, Flower
R.J.Pharmacology. 6th ed.Elsevire: Churchill
livingstone;2008:[226-237
• http://www.medindia.net/articles/prolactin.htm
• http://en.wikipedia.org/wiki/prolactin
19

20. THANK YOU
20