This document provides information about prolactin secretion and hyperprolactinemia. It discusses the physiology and regulation of prolactin, including its pulsatile secretion under inhibitory hypothalamic control. It describes the functions of prolactin in reproduction and lists some of its other roles. Regarding hyperprolactinemia, it identifies potential causes, outlines the diagnostic process, and discusses treatment with dopamine agonists like bromocriptine and cabergoline to lower prolactin levels and improve symptoms.

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