1. ISAR ONLINE
POST-GRADUATE COURSE
DR. LIPIKA MOHARANA

2. QUESTION
• Describe the physiology and regulation of
prolactin secretion..
• What are the functions of prolactin in
reproduction??
• What are the causes of hyper-prolactinemia
and how do you manage it??

3. OUTLINE
• Introduction
• Physiology of prolactin
secretion
• Regulation of prolactin
secretion
• Role of prolactin in
reproduction
• Hyper-prolactinemia- Causes,
Diagnosis, Management

4. Introduction
• Human PRL is a single-chain
polypeptide of 199 amino acids. It
has a molecular weight of 23 kDa.
Half-life 20-30mins, single gene
regulation on Chromosome 6
• Prolactin is synthesized in and
secreted from specialized cells of
the anterior pituitary gland, the
lactotroph(acidophilic) cells.
• More than 300 effects in the body,
mostly through modulation

5. Introduction
• Unique- Only under
hypothalamic control & does not
depend on any negative
feedback by peripheral
hormones, the only ant pituitary
hormone that doesn’t have an
endocrine target organ
• Forms:- Little PRL(23kDa, major
circulating form, biologically &
immunologically active), Big
PRL(50kDa) & Big-Big PRL(100-
150kDa, tetrameric, macroPRL,
highly immunogenic, low biologic
activity)

6. Molecular micro-heterogeneity

7. Physiology
• Secretion is mostly pulsatile under inhibitory
hypothalamic control. At molecular level
prolactin acts more as a cytokine & growth
factor, than like a hormone with no second
messenger molecule
• 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.
• After parturition prolactin induce breast milk
proteins transcription

8. Physiology
• Reproductive; inhibition of ovulation by decreasing
secretion of LH and FSH (inhibits GnRH pulse release)
• Regulation of immune system; by stimulating T-cell & B-
cell functions.
• Osmo-regulation; 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 oligo-
dendrocytes, the cells responsible for the formation of
myelin coatings on axons in the central nervous system.

10. Prolactin
Related
Functions
Immuno-modulation
Gonadal Function
Hepatic Bile
production
Lactogenesis
Anxiety
Parental
Behaviour
Neuro-genesis
Lipid
metabolism,
food intake
& weight gain

11. Regulation
• The primary control of PRL is inhibitory. Counter-
current flow in the hypothalamo-hypophyseal portal
system initiates secretion of Dopamine (principal
prolactin inhibiting factor) acting on the D2
receptors present on the lactotroph cells
• Triggered by the prolactin releasing hormone (PRH)
• 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. Breast feeding is the major stimulus of
prolactin production.

12. Regulation
• In hypothyroidism, raised
Thyro-tropin releasing
hormone
(TRH) acts of lactotroph
receptors in anterior
pituitary to increase
release of PRL
• Most of the signs and
symptoms of
hypothyroidism & hyper-
prolactinemia are
associated with each
other

14. Miscellaneous factors regulating PRL
secretion

15. Summary of PRL Actions & Regulation

16. Role in Reproduction
• PRL has significant actions in male & female reproduction
• In females, incr. PRL reduces GnRH pulse frequency, lowers FSH & LH
levels, causing oligi/anovulation, increased FSH levels compared to LH,
increases adrenal DHEAS levels causing follicular maturation arrest(cysts)
• In males, incr. PRL(mostly due to stress), lower levels of FSH & LH cause
decreased testosterone levels(decr. libido) & impaired spermatogenesis in
seminiferous tubules
• Lower levels of PRL affect parental behaviour & parental care & rearing of
the off-spring.

17. PRL & Male Reproduction
• Decreased libido
• Impotence
• Inefficient sperm
production (sub-normal
semen parameters)
• Infertility

18. PRL & Female Reproduction
• Oligo/an-ovulation
• Follicular maturation arrest (Follicular
cysts)
• Increased DHEAS levels, increased
recruitment of follicles arrested in
growth
• Decreased libido
• Infertility
• Associated Hypothyroidism & PCOS

19. Range of raised PRL symptoms in Females

20. HYPER-PROLACTENEMIA
CAUSES , SIGNIFICANCE, DIAGNOSIS &
MANAGEMENT

21. Effects
 Stimulate dopamine turnover in some brainareas
 Nucleus accumbens
 Decrease dopamine turnover in some brainareas
 Substantia nigra
 Stimulate learning
 Stimulate immune response
 Stimulate oxytocin
 Stimulate opioidergic system
 Decrease gonadotropins
 Decrease testosterone in male(indirect)
 Decrease libido in both sex (impotence)
 Reduce bone mineral density (osteoporosis)

22. Diagnosis
• Secretion of PRL is pulsatile
• Secretion follows a circadian rhythm, higher
concentration during night & lower during the day
• Normal levels typically in women are 10-25ng/ml
• Preferably a fasting sample, drawn 2hours after waking
up
• Common physiological conditions & drugs that raise
PRL levels, should be ruled out.
• Ideally routine screening of macroprolactinemia may
be of help in asymptomatic patients
• Macroprolactinemia screening can be done nowadays
by PEG, GFC, A/G Colun & 125 I PRL binding site tests.

23. Measurement of PRL
• A simple blood test drawn
• First thing in the morning: be awake 2
hours before the test.
• Early in the menstrual cycle – before
ovulation. This is because prolactin levels
are naturally higher after ovulation.
• Be 8-10 hours of fasting prior to
extraction.
• Be relaxed and rested for at least 30 min
before extraction.
• Avoids:
• High-protein or fat diet: 24 hours
• Intercourse: 24 hours
• Stimulation of the breast and nipples: 24
hours
• Stress: physical examination: 24 hours.

24. Values
• 5-20 ng/mL is considered normal in both sexes.
• 20 ng/mL males
• 25 ng/mL females.
• During pregnancy and lactation: upto 200-400 ng/mL
• > 20 ng/mL in two successive measurements is defined
as hyperprolactinemia
• > 250 ng/mL usually indication for prolactinoma.
• > 500 ng/mL it is considered as diagnosis for
macroprolactinoma
Conversion factor: mU/l × 0,0472 =ng/ml; ng/ml × 21,2 = mU/l.)

25. Comparision of different diagnostic methods

26. Causes of Hyper-Prolactinemmia

27. Pathological Hyper-Prolactinemia

28. Work-Up

29. Dopamine Agonists
Aim is to
 Lower PRL levels
 Decrease tumour size
 Improve male & female
gonadal functions
Dopamine agonists are
Bromocriptine, Cabergoline,
Lisuride, Pergolide,
Quinagolide

30. Bromocriptine
• It is an effective and inexpensive medication for high
prolactin levels.
• Dose-2.5-5mg/day, follow up after 6-8weeks
• Side-effects-Nausea & vomiting, back pains, oedema,
hallucinations, motor fluctuations
• The prolactin levels can be rechecked in 3 weeks. If the
levels are still elevated the dose can be increased or a
different medication can be tried.
• Due to the side effects, some women can not tolerate
it:
• Vaginal bioadhesive suppositories
• Vaginal use of the pill

31. Cabergoline
• Longer acting medication
• Dose-0.25-0.5mg/week for 6-8
weeks.Re-evalation after
completion of course
• Side-effects-hypotension,
nausea,vomiting, motor
fluctuations
• Systematic reviews: Cabergoline
is more effective than
bromocriptine in achieving
normoprolactinemia and
resolving amenorrhea/
oligomenorrhea and
galactorrhea.

32. Conclusion
• Prolactin is the hormone responsible for
lactogenesis
• It’s secreted in a pulsatile manner from the
acidophil lactotrophs of anterior pituitary, mainly
under inhibitory hypothalamic control
• It’s the only hormone with no endocrine end
organ & hence not under any negative feedback
from peripheral hormones
• Multiple physiological roles in the body apart
from lactogenesis & gonadal functioning,
including immuno-modulation, regulation of bone
density, neurogenesis, lipid metabolism &
electrolyte balance

33. Conclusion
• Raised PRL levels can cause various organ &
metabolic dysfunctions, especially
reproductive dysfunction in both males &
females
• Evaluation/Interpretation of
hyperprolactinemia should be done after
excluding physiological causes & drugs
• Dopamine agonists can help in alleviating
symptoms, lowering PRL levels & reducing
tumour size, if any.

34. THANK YOU