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REGULATION OF LACTOGENIC HORMONES
BY
DEVI PRIYA SUGATHAN
MSC BIOCHEMISTRY AND
MOLOCULAR BIOLOGY
What are lactogenic hormones ?
• The hormones which stimulate growth of
mammary glands and lactation after parturition.
• From the 24th week of pregnancy, the women’s
body produces hormones that stimulate the
growth of the milk duct system in the breast.
• Lactogens – any agent [hormone] that enhances
milk production. Eg: prolactin, human chorionic
somatomammotropin.
Key Female Hormones
Gonadotropin releasing hormone
Follicle stimulating hormone
Luteinizing hormone
Estrogen
Progesterone
Prolactin
Milk Production
• Milk production potential is a function of the
number of mammary epithelial cells in the gland.
• Therefore, improved lactation performance can be
achieved under conditions that enhance mammary
cell proliferation (or decrease apoptosis),
biochemical and structural differentiation of
mammary epithelium, and synthesis and secretion
of milk components.
• There are various hormones that are involved in
these processes.
Lactation Hormones
MAMMOGENIC LACTOGENIC LACTOPOEITIC
• Estrogen
• Progesterone
• Prolactin
• Growth hormone
• Human Placental
Lactogen[HCS]
• Prolactin
• Insulin
• Glucocorticoids
• Growth hormone
• Glucocorticoids
• Thyroid hormone
• Prolactin
• Parathyroid hormone
• Insulin
• Oxytocin
Prolactin – Key Lactogenic Hormone
• Prolactin is a protein of 198 aminoacids secreted from the
anterior pituitary.
• Prolactin secretion is stimulated by PRH and repressed by
estrogen, progesterone and dopamine from
hypothalamus.
• The level of prolactin in serum increases during pregnancy
and causes enlargement of the mammary gland and
prepare it for milk production.
• Estrogen in pregnancy helps to increase prolactin.
PRL has a wide
variety of target
tissues, including
mammary gland,
prostate, ovary, cells
of the immune
system, adipocytes,
liver, and other
tissues.
PRL Receptors• The prolactin receptor interacts with prolactin as a transmembrane
receptor.
• It is a cytokine receptor and second messenger cascades include the
JAK-STAT pathway, JAK-RUSH pathway, Ras-Raf-MAPK pathway.
• It contains an extracellular region that binds prolactin, a transmembrane
region and a cytoplasmic region.
• The PRLR also binds and is activated by GH and hPL.
• As a result of the signal transduction pathways, prolactin stimulates
uptake of some aminoacids, the synthesis of milk proteins casein and α-
lactalbumin, uptake of glucose and synthesis of the milk sugar lactose
as well as milk fats.
Regulation through Jak - Stat Pathway
• Milk protein genes are regulated by lactogenic hormones,
through a cascade of events mediated by Jak/Stat5.
• This intracellular signaling pathway transfers information
from the cell membrane receptor to the nucleus.
• Once the lactogenic hormone binds to the membrane
receptor two Jak molecules become phosphorylated
which subsequently phosphorylates Stat5.
• The Stat5 factor transfers to the nucleus to bind a
conserved DNA sequence motif, GAS [ milk protein
genes].
• This mechanism is suppressed by SOCS3. The
activated Stats5 stimulate the transcription of gene
SOCS3 which inhibit Jak and as a result the
pathway is turned off [ negative feedback].
• Therefore progesterone inhibits lactation by
interfering with prolactin receptor/ Stat5 signalling
and blocks Stat5 from binding to GAS.
Prolactin level varies according to:
• Level of prolactin is higher at night.
• Prolactin levels are at the highest until two months postpartum..
• Prolactin levels increase if more milk is removed from the breast.
• Women who smoke have low prolactin levels.
• Stress and anxiety may increase prolactin levels.
• High prolactin levels are inclined to delay ovulation.
Insulin
• Insulin causes the nonsecretory epithelia to undergo
cell division in late pregnancy. This cell division seems
to be necessary for lactogenesis to occur.
• IGF-1 may be the primary mitogen involved in this cell
division leading up to lactogenesis.
• Both insulin and the IGFs may be involved in glucose
uptake by the mammary cells.
• This glucose uptake is of critical importance for lactose
synthesis.
• Insulin also may be directly involved in expression of
milk protein genes.
Glucocorticoids
• Glucocorticoids are required for full initiation of milk secretion.
• They seem to be involved in development of the RER and other
ultrastructural changes required for massive protein synthesis.
• They also may be directly involved in transcription of the casein
and α-lactalbumin genes.
• Increased uptake of glucocorticoid by the mammary tissue coincides
with lactogenesis.
• Glucocorticoid receptors in the mammary cells increase in numbers
in late pregnancy.
• It is also known as Human chorionic
somatomammotropin.
• It is a hormone produced from the placenta.
• It mimics the action of prolactin and binds to
the prolactin receptor.
• HPL gets released from the second month of
pregnancy and is involved in the growth and
development of breast, nipple and areola
before birth.
Human Placental lactogen
Estrogen
• All through pregnancy, the large quantities of
estrogens secreted by the placenta cause the
ductal system of the breasts to grow and
branch.
• Simultaneously, the stroma of the breasts
increases in quantity, and large quantities of fat
are laid down in the stroma.
• High levels of estrogen inhibit lactation.
Estrogen levels also drop at delivery and remain
low for the first several months of breastfeeding.
Progesterone
• Final development of the breasts into milk secreting organs
requires progesterone.
• Once the ductal system has developed , progesterone
causes additional growth of the breast lobules, with
budding of alveoli and development of secretory
characteristics in the cells of the alveoli.
• High levels of progesterone inhibit lactation before
birth.
• Progesterone levels drop after birth; this triggers the onset
of copious milk production.
• Prolactin and Human placental lactogen promotes the production of milk but
no more than a few milliliters of fluid are secreted each day until after the baby
is born.
• This is due to the suppressive action of estrogen and progesterone produced
during the pregnancy.
• Immediately after the baby is born, the sudden loss of both estrogen and
progesterone, allows the lactogenic effect of prolactin from the mother’s
pituitary gland to assume its natural milk promoting role, and over the next 1
to 7 days, the breasts begin to secrete copious quantities of milk .
• The fluid secreted during the last few days before and the first few days after parturition is
called colostrum; it contains essentially the same concentrations of proteins and lactose as milk,
and has no fat.
• Secretion of milk requires an adequate background secretion of most of the mother’s other
hormones as well, but most important are growth hormone, cortisol, parathyroid hormone, and
insulin. These hormones are necessary to provide the amino acids, fatty acids, glucose, and
calcium required for milk formation.
• If this prolactin surge is absent or blocked as a result of hypothalamic or pituitary damage or if
nursing does not continue, the breasts lose their ability to produce milk within 1 week or so.
• However, milk production can continue for several years if the child continues to suckle,
although the rate of milk formation normally decreases considerably after 7 to 9 months.
Oxytocin – Ejection or ‘let down’ process in milk secretion.
• A type of neurosecretory cells in the posterior pituitary gets
stimulated by suckling and would release oxytocin.
• When the baby suckles, it receives virtually no milk for the
first half minute.
• Sensory impulses must first be transmitted through somatic
nerves from the nipples to the mother’s spinal cord and then
to her hypothalamus, where they cause nerve signals that
promote oxytocin.
• Oxytocin is carried in the blood to the breasts, where it
causes myoepithelial cells to contract, thereby
expressing the milk from the alveoli into the ducts at a
pressure of +10 to 20 mm Hg.
• Then the baby’s suckling becomes
effective in removing the milk.
• Thus, within 30 seconds to 1 minute after a
baby begins to suckle, milk begins to flow.
• This process is called milk ejection or
milk let-down.
• The sucking action of a nursing infant
causes a reduction in hypothalamic
secretion of dopamine (PIH).
• This increases prolactin secretion and
stimulating milk production in the breast.Suckling on one breast causes milk flow not only in that
breast but also in the opposite breast.
Hearing the baby crying often gives enough of an emotional
signal to the hypothalamus to cause milk ejection.