FEMALE REPRODUCTIVE SYSTEM
FEMALE REPRODUCTIVE SYSTEM
 TO REVIEW THE COMPONENTS OF THE
FEMALE REPRODUCTIVE SYSTEM
 TO CHARACTERIZE THE GENERAL
ORGANIZATION OF THE OVARIES
 TO UNDERSTAND THE HORMONAL
REGULATION OF OOGENESIS, OVULATION,
AND THE UTERINE CYCLE
Hormones of the Female
Reproductive Cycle
• Control the reproductive cycle
• Coordinate the ovarian and uterine cycles
Hormones of the Female
Reproductive Cycle
• Key hormones include:
– FSH
• Stimulates follicular development
– LH
• Maintains structure and secretory function of corpus
luteum
– Estrogens
• Have multiple functions
– Progesterones
• Stimulate endometrial growth and secretion
FEMALE REPRODUCTIVE SYSTEM
 OVARIES
 OVIDUCT (UTERINE TUBES)
 UTERUS
 VAGINA
Female Reproductive Organs
• Ovary: female gonad
• Uterine Tubes (fallopian tube, oviduct)
- three parts: infundibulum, ampulla, isthmus
The Female Reproductive System in Midsagital View
Figure 28.13
The Ovaries and Their Relationships to the
Uterine Tube and Uterus
Figure 28.14a, b
The Uterine Tubes
Figure 28.17a-c
The Uterus
• Muscular organ
– Mechanical protection
– Nutritional support
– Waste removal for the developing embryo and fetus
• Supported by the broad ligament and 3 pairs of
suspensory ligaments
Uterine Wall Consists of 3
Layers:
• Myometrium – outer muscular layer
• Endometrium – a thin, inner, glandular mucosa
• Perimetrium – an incomplete serosa continuous
with the peritoneum
• The site of implantation of developing embryo
• And 3 parts: fundus, body, and cervix
Female Accessory Sex Organs: Uterus
• Uterine endometrium has two layers:
- basal layer
- functional layer: built up and shed each cycle
The Uterus
Figure 28.18a, b
The Uterus
Figure 28.18c
The Uterine Wall
Figure 28.19a
The Uterine Wall
Figure 28.19b
The Uterine Cycle
To be discussed below
Figure 28.20
Functions of the Ovary
• Production of a mature oocyte, capable of
fertilization and embryonic development.
• Production of ovarian steroids (estradiol,
progesterone).
• Production of gonadal peptides (inhibin, activin).
Structural Organization of the Ovary
• The main functional unit of the ovary is the
follicle.
• Follicles are composed of the oocyte,
granulosa cells, and theca cells.
Stages of Follicular Growth
• Follicles are present in a number of
different stages of growth:
- primordial follicles (resting)
- primary, secondary, and antral follicles
- preovulatory (Graafian) follicles
The Corpus Luteum
• After the preovulatory follicle ovulates
(releases its egg), it forms the corpus
luteum.
FEMALE REPRODUCTIVE SYSTEM
 OVIDUCT (UTERINE TUBES)
INFUNDIBULUM, AMPULLA, ISTHMUS, UTERINE
 UTERUS
FUNDUS, BODY (CORPUS), CERVIX
Oogenesis and Oocyte Maturation
• Recall that germ cells must go through meiosis in
order to produce unique haploid cells.
• From one spermatogonia, end up with four
spermatozoa.
• Oocytes must also go through meiosis, but they do
it during the course of follicular development.
• Primordial follicles contain primary oocytes that
are arrested in prophase I, prior to the first meiotic
division (diploid).
• How do they go through the rest of meiosis?
Oocyte Maturation
• Oocytes remain in prophase I until the
preovulatory surge of LH, which initiates
completion of the first meiotic division.
• The primary oocyte does not split into two cells,
but instead gives off a very small first polar body,
containing half of the chromosomes.
LH surge
zona pellucida
first polar body
Oocyte Maturation
• Thus, the ovulated “egg” is actually not completely
mature (hasn’t completed meiosis II).
• Maturation goes to completion only if the oocyte is
fertilized.
• Fertilization causes completion of meiosis II, and
expulsion of a second polar body.
• Meiosis of the oocyte results in only one gamete.
fertilization
first polar body
first polar body
second polar body
FEMALE REPRODUCTIVE SYSTEM
 OVARY
GERMINAL EPITHELIUM
TUNICA ALBUGINEA
- thin connective tissue capsule
underlying germinal epithelium
CORTEX
- surrounds the medulla and
contains maturing follicles
MEDULLA
- central connective tissue
containing vascular supply and
nervous innervation
The Ovarian Cycle
FEMALE REPRODUCTIVE SYSTEM
 OVARY
The Ovarian Cycle
3 to 5 million OOGONIA differentiate into
PRIMARY OOCYTES during early development
OOCYTES becomes surrounded by squamous
(follicular) cells to become PRIMORDIAL FOLLICLES
most PRIMORDIAL FOLLICLES undergo
atresia leaving 400,000 at birth
oocytes at birth arrested at
Meiosis I (prophase)
FEMALE REPRODUCTIVE SYSTEM
 OVARY
THREE STAGES OF OVARIAN FOLLICLES CAN
BE IDENTIFIED FOLLOWING PUBERTY:
(each follicle contains one oocyte)
(1) PRIMORDIAL FOLLICLES
OOGENESIS
- very prevalent; located in the
periphery of the cortex
- a single layer of squamous follicular
cells surround the oocyte
(2) GROWING FOLLICLES
- three recognizable stages:
(a) early primary follicle
(b) late primary follicle
(c) secondary (antral) follicle
(3) MATURE (GRAAFIAN) FOLLICLES
- follicle reaches maximum size
FEMALE REPRODUCTIVE SYSTEM
 OVARIAN FOLLICLES
(1) PRIMORDIAL FOLLICLES
(2) GROWING FOLLICLES
(a) early primary follicle
- follicular cells still unilaminar but now are cuboidal in appearance
- oocyte begins to enlarge
(b) late primary follicle
- multilaminar follicular layer; cells now termed granulosa cells
- zona pellucida appears; gel-like substance rich in GAGs
- surrounding stromal cells differentiate into
theca interna and theca externa
(b) secondary (antral) follicle
- cavities appear between granulosa cells forming an antrum
- follicle continues to grow
- formation of cumulus oophorus and corona radiata
(3) MATURE (GRAAFIAN) FOLLICLES
FEMALE REPRODUCTIVE SYSTEM
 OVARIAN FOLLICLES
late primary follicle
FEMALE REPRODUCTIVE SYSTEM
 OVARIAN FOLLICLES
GRANULOSA (FOLLICULAR) CELLS
OOCYTE
ZONA PELLUCIDA
FEMALE REPRODUCTIVE SYSTEM
 OVARY
CORTEX
MEDULLA
CORPUS LUTEUM
FEMALE REPRODUCTIVE SYSTEM
TUNICA ALBUGINEA
GERMINAL EPITHELIUM
CORTEX
 OVARY
PRIMORDIAL
FOLLICLES
TUNICA ALBUGINEA
GERMINAL EPITHELIUM
FEMALE REPRODUCTIVE SYSTEM
 OVARY
FEMALE REPRODUCTIVE SYSTEM
 OVARY
OVARY
H&E
PRIMORDIAL
FOLLICLES
EARLY 1º
FEMALE REPRODUCTIVE SYSTEM
 OVARY
OVARY
H&E
CORPUS
ALBICANS
EARLY PRIMARY
FOLLICLES
PRIMORDIAL
FOLLICLE
FEMALE REPRODUCTIVE SYSTEM
 OVARY
LATE PRIMARY FOLLICLE
multilaminar
FEMALE REPRODUCTIVE SYSTEM
 OVARY
MATURE (GRAAFIAN) FOLLICLE
zona pellucida
cumulus oophorus
corona radiata
theca interna and externa
theca interna cells begin to
produce androgens that are
converted to estrogens
FEMALE REPRODUCTIVE SYSTEM
 HORMONAL REGULATION OF
OOGENSIS AND OVULATION
HYPOTHALAMUS release of GnRF which
stimulates release of LH and FSH from the
adenohypophysis (ANTERIOR PITUITARY)
Neuroendocrine Regulation of Ovarian
Functions
CNS
hypothalamus
GnRH
Pituitary
FSH
LH
E2, P
inhibin,
activin
OVARY
Follicle
Development
Ovulation
Luteinization
Effects of GnRH on Gonadotropins
• GnRH is released in a pulsatile manner,
stimulating the synthesis and release of LH and
FSH.
• GnRH acts through its receptor on the pituitary
gonadotroph cells, stimulating production of
phospholipase C.
• Recall that IP3 pathway causes gonadotropin
release, while the DAG/PKC pathway causes
gonadotropin synthesis.
Actions of FSH on Granulosa Cells

FSH

AC
ATP
cAMP
Gs
Gene Expression
Steroidogenic
enzymes
PKA
LH Receptor
CREB
CRE
Inhibin Subunits
Plasminogen
Regulation of Estradiol Production
• Recall the two-cell theory of estradiol production
(lecture 4):
- LH acts on theca cells to produce androgens
- FSH acts on granulosa cells to increase
aromatase activity, resulting in conversion of
androgens to estrogens
(granulosa cells lack 17 hydroxylase activity)
Ovarian Estradiol Production
LH
Theca cells
androgens
aromatase
Granulosa cells
FSH
estradiol
Regulation of Progesterone Production
• Progesterone is produced from theca cells, mature
granulosa cells, and from the corpus luteum.
• In this case, gonadotropins induce expression of
- steroidogenic acute regulatory protein
- P450 side chain cleavage
Actions of Estradiol
• Estradiol plays an important role in feedback
regulation of gonadotropin release.
• Low estradiol levels exert negative feedback (via
inhibition of GnRH release)
Question: what happens to LH and FSH levels if you
remove the ovary (increase, decrease, no change)?
Answer:
Actions of Estradiol
• High estradiol levels exert positive feedback (via
increase in GnRH receptors, stimulation of GnRH
release, increased pituitary response to GnRH, and
effects on LH)
- increase in stimulatory neurotransmitters
regulating GnRH neurons (ie, norepinephrine)
- decrease in inhibitory neurotransmitters (ie, beta
endorphin)
- increased activity of GnRH neurons
- increased expression of GnRH receptors
- increased expression of LH gene
Actions of Estradiol
• Estradiol also has important actions in a number of
other tissues:
- causes proliferation of uterine endometrium
- increases contractility of uterine myometrium
- stimulates development of mammary glands
- stimulates follicle growth (granulosa cell
proliferation)
- effects on bone metabolism, hepatic lipoprotein
production, genitourinary tract, mood, and cognition
• Effects are mediated through the intracellular
estrogen receptors (alpha and beta), and possible
membrane effects.
Actions of Progesterone
• Progesterone exerts positive and negative
feedback effects on gonadotropin synthesis and
release.
• Progesterone also acts on many tissues:
- stimulates secretory activity of the uterine
endometrium
- inhibits contractility of the uterine myometrium
- stimulates mammary growth
• The actions of progesterone are mediated through
an intracellular P receptor, which acts as a
transcription factor.
Regulation of Follicle Growth
• Primordial follicles can “rest” for many decades
before being recruited for growth by an unknown
mechanism.
• The recruitment of primordial follicles and
subsequent growth to the small antral follicle stage
can occur without gonadotropin stimulation
(gonadotropin-independent).
• Small antral follicles (and larger) must be
stimulated by FSH and LH in order to continue
growth to the preovulatory stage (gonadotropin
dependent).
Regulation of Follicle Growth
• Each day many follicles begin to grow
(recruitment).
• Each cycle, only one follicle is “selected” for
continued development to the preovulatory stage,
by an unknown mechanism.
• This follicle is called the dominant follicle
• The remaining recruited follicles become atretic
and degenerate.
Regulation of Follicle Growth
recruitment
selection
preovulatory
follicle
atresia
Follicular Ovulation
• As the preovulatory follicle grows, it produces
increasing amounts of estradiol.
• When the preovulatory follicle is mature, plasma
estradiol levels are very high.
• High estradiol levels exert positive feedback on
the hypothalamus and pituitary, resulting in LH
and FSH surges.
• These preovulatory gonadotropin surges cause
ovulation of the preovulatory follicle (follicular
rupture and release of the egg for fertilization).
Mechanism of Gonadotropin-induced
Ovulation
• The preovulatory LH and FSH surges induce
expression of enzymes in the preovulatory follicle
which break down the follicle wall.
• Tissue-type plasminogen activator: results in
breakdown of fibrin.
• Metalloproteinases: result in breakdown of
collagen.
• Result: follicle wall is ruptured, resulting in
release of the oocyte into the peritoneal cavity.
Formation of the Corpus Luteum
• After the follicle ovulates, the remaining granulosa
cells and theca cells luteinize.
• Luteinization: accumulation of cholesterol and
lipid, cells swell.
• Luteinized cells switch the ovary from
predominant production of estradiol to production
of progesterone and estradiol.
• This prepares the uterine endometrium for
pregnancy.
FEMALE REPRODUCTIVE SYSTEM
The Menstrual Cycle
 HORMONAL REGULATION OF OOGENSIS AND OVULATION
FOLLICULAR PHASE
OVULATION
LUTEAL PHASE
10-20 primordial follicles begin to develop
in response to FSH and LH levels
theca and granulosa cells transform into the corpus
luteum and secrete large amounts of progesterone
FSH and LH stimulate theca and granulosa
production of estrogen and progesterone
if fertilization does not occur, corpus luteum
degenerates ... if fertilization does occur, HCG
released from the embryo maintains corpus luteum
surge of LH induces ovulation
FEMALE REPRODUCTIVE SYSTEM
The Menstrual Cycle
 HORMONAL REGULATION OF OOGENSIS AND OVULATION
OVULATION:
sharp surge in LH
with simulataneous
increase in FSH
Meiosis I resumes;
oocyte and surrounding
cumulus break away and
are extruded
oocyte passes into
oviduct
ECTOPIC
IMPLANTATIONS
The Menstrual Cycle
• Women have ovulatory cycles of about 28 days in
length.
• Day 1 of the cycle is defined as the first day of
menstruation.
• There are two phases of the cycle, named after
ovarian and uterine function during that phase:
- first two weeks: follicular or proliferative stage
- second two weeks: luteal or secretory stage
• The preovulatory gonadotropin surges occur in the
middle of the cycle (around day 14).
The Menstrual Cycle: The Ovary
• Follicular phase: small antral follicles develop, a
dominant follicle is selected and grows to the
preovulatory stage.
• Midcycle: the gonadotropin surges cause
ovulation of the dominant follicle.
• Luteal phase: the corpus luteum forms and
becomes functional, secreting large amounts of
progesterone, followed by estradiol (results in
negative feedback, not positive feedback, because
P increases before E2).
• If pregnancy does not take place, the corpus
luteum regresses, and P and E2 levels decrease.
The Menstrual Cycle: The Uterus
• Proliferative stage: increasing estradiol levels
stimulate proliferation of the functional layer of
the uterine endometrium.
- Results in increased thickness of the
endometrium.
- Increased growth of uterine glands (secrete
mucus) and uterine arteries.
• Secretory stage: progesterone acts on the
endometrium.
- uterine glands become coiled and secrete more
mucus
- uterine arteries become coiled (spiral arteries)
The Menstrual Cycle: The Uterus
• If pregnancy doesn’t occur, P and E2 levels
decrease at the end of the secretory stage.
- vasospasm of arteries causes necrosis of tissue
- loss of functional layer with bleeding of uterine
arteries (menstruation)
FEMALE REPRODUCTIVE SYSTEM
 CORPUS LUTEUM
FORMED FROM FOLLICLE WALL WHICH
REMAINS FOLLOWING OVULATION
TRANSFORMED CELLS SECRETE
ESTROGENS AND PROGESTERONE:
(1) GRANULOSA LUTEIN CELLS
- large, light cells derived from
granulosa cells
(2) THECA LUTEIN CELLS
- strands of small cells derived from
theca interna
FEMALE REPRODUCTIVE SYSTEM
 CORPUS LUTEUM
(1) GRANULOSA LUTEIN CELLS
CORPUS LUTEUM
H&E
(2) THECA LUTEIN CELLS
(1)
(2)
FEMALE REPRODUCTIVE SYSTEM
 OVIDUCT
TRANSMITS OVA FROM
OVARY TO UTERUS
MEIOSIS II IN PROGRESS AND ULTIMATELY
ARRESTS UNLESS FERTILIZED
SITE OF FERTILIZATION
MUCOSA
EPITHELIUM AND LAMINA PROPRIA
MUSCULARIS
INNER CIRCULAR; OUTER LONGITUDINAL
INCREASES AS APPROACH UTERUS
SEROSA
FEMALE REPRODUCTIVE SYSTEM
 OVIDUCT
SIMPLE COLUMNAR EPITHELIUM
TWO CELL TYPES:
(1) CILIATED
(2) PEG CELLS (NONCILIATED)
FEMALE REPRODUCTIVE SYSTEM
 UTERUS
PERIMETRIUM, MYOMETRIUM, ENDOMETRIUM
FEMALE REPRODUCTIVE SYSTEM
 UTERUS
ENDOMETRIUM
undergoes cyclic changes which prepare
it for implantation of a fertilized ovum
TWO LAYERS:
(1) FUNCTIONAL LAYER (stratum functionalis)
- BORDERS UTERINE LUMEN
- SLOUGHED OFF AT MENSTRATION
- CONTAINS UTERINE GLANDS
(2) BASAL LAYER (stratum basale)
- RETAINED AT MENSTRATION
- SOURCE OF CELLS FOR REGENERATION OF
FUNCTIONAL LAYER
STRAIGHT AND SPIRAL ARTERIES
FEMALE REPRODUCTIVE SYSTEM
 HORMONAL REGULATION OF UTERINE CYCLE
(1) PROLIFERATIVE PHASE
concurrent with follicular maturation and influenced by estrogens
(2) SECRETORY PHASE
concurrent with luteal phase and influenced by progesterone
(3) MENSTRUAL PHASE
commences as hormone production by corpus luteum declines
FEMALE REPRODUCTIVE SYSTEM
 UTERUS
PROLIFERATIVE PHASE
cells in basal layer begin to
proliferate to regenerate
functional layer
spiral arteries begin to lengthen
and revascularize developing layer
functional layer becomes thicker
than basal layer during late
proliferative phase
developing uterine glands are
tubular in arrangement
FEMALE REPRODUCTIVE SYSTEM
 UTERUS
PROLIFERATIVE PHASE
tubular uterine glands
simple columnar lining
FEMALE REPRODUCTIVE SYSTEM
 UTERUS
PROLIFERATIVE PHASE
tubular uterine glands
UTERUS
H&E
PROLIFERATIVE PHASE
simple columnar lining
UTERINE
GLANDS
FEMALE REPRODUCTIVE SYSTEM
 UTERUS
SECRETORY PHASE
functional layer thickens
glands become coiled and
accumulate large quantities of
secretory product
FEMALE REPRODUCTIVE SYSTEM
 UTERUS
SECRETORY PHASE
UTERUS
H&E
SECRETORY PHASE
functional layer thickens
glands coiled
COILED
UTERINE
GLANDS
FEMALE REPRODUCTIVE SYSTEM
 UTERUS
SECRETORY PHASE
functional layer thickens
glands become coiled and
accumulate large quantities of
secretory product
FEMALE REPRODUCTIVE SYSTEM
 VAGINA
MUCOSA
STRATIFIED SQUAMOUS EPITHELIUM
LAMINA PROPRIA
---------------- no glands ---------------MUSCULARIS
INNER CIRCULAR
OUTER LONGITUDINAL
ADVENTITIA
FEMALE REPRODUCTIVE SYSTEM
 LABIA MINORUM
LABIA MINORUM
H&E
Endocrinology of Pregnancy
• To maintain the uterine endometrium and inhibit
contraction of myometrium, must maintain plasma
progesterone levels during pregnancy.
• Early in pregnancy, this is accomplished by the
action of human chorionic gonadotropin (hCG) on
the corpus luteum (first 8 weeks of pregnancy).
• Later in pregnancy, progesterone is produced by
the placenta.
Early Embryonic Development
• After fertilization, the embryo spends the first four
days in the oviduct (fallopian tube).
• The developing embryo then goes to the uterus,
and implants in the uterine endometrium on Day 6
(blastocyst stage of development).
• By day 6, the trophoblast cells of the embryo
begin to produce hCG.
• In a normally developing embryo, hCG levels (in
maternal circulation) will double every 3 days,
reaching peak at about 2 months of pregnancy.
Actions of Human Chorionnic
Gonadotropin (hCG)
• hCG binds to the LH receptor in the corpus
luteum, maintaining luteal steroidogenesis during
the first 8 weeks of pregnancy.
• In addition, hCG may act to stimulate testosterone
production from the developing testes in male
embryos.
Role of the Fetal-Placental-Maternal
Unit in Steroid Production
• Later in pregnancy, the placenta becomes the major
steroidogenic organ of pregnancy.
• However, the placenta requires maternal LDL as a
source of cholesterol for progesterone production.
• The placenta also produces estrogens during
pregnancy (primarily estriol). However, the placenta
is dependent upon the maternal and fetal adrenal as a
source of androgens for aromatization to estrogen.
• Estrogens may be important in increasing uterine
blood flow to the fetus, and in the maturation of fetal
organ systems.
Parturition: The Process of Childbirth
• The mechanisms signaling the onset of labor are
not clearly understood, although several theories
exist.
• Potential role of progesterone?:
- decreasing progesterone prior to labor would
allow uterine contractions to occur
- however, there is no decline in progesterone
before labor in humans
- some studies suggest there is a decline in uterine
progesterone receptors, resulting in decreased
progesterone action, leading to labor
Potential Role of Oxytocin in
Parturition?
• Oxytocin causes uterine contraction.
• However, oxytocin levels do not increase until
after labor starts, according to more recent studies.
• Oxytocin may play a role in uterine contraction
following labor, resulting in decreased blood loss.
Potential Role of Relaxin in Parturition?
• Relaxin acts on the cervix, causing dilatation and
softening.
• In some animals relaxin increases before labor
starts.
• In humans, relaxin is high beginning early in
pregnancy and stays elevated until labor.
• Relaxin does act to soften connective tissues, such
as the ligaments connecting the pelvic bones, to
allow increase in size of the birth canal.
• Relaxin also decreases uterine contractility during
pregnancy.
Potential Role of Prostaglandins in
Parturition
• Prostaglandins cause dilation and softening of the
cervix.
• Prostaglandins also cause uterine contractions.
• The levels of prostaglandins increase in fetal
membranes before the onset of labor.
• It is believed that some (unknown) signal from the
fetus causes increased prostaglandin production
from fetal membranes, which then act on the
uterus and cervix to initiate labor.
Lactation
• Lactation is the delivery of milk from the
mammary gland.
• There are four main stages of lactation, controlled
by different hormones:
- milk synthesis in alveolar cells
- secretion of milk from alveolar cells to alveolar
lumen
- maintainance of established milk production and
release into alveolar lumen
- milk ejection: movement of milk from alveoli
into the duct system and out of the breast
Lactation: Milk Synthesis
• Milk Synthesis: Production of breast milk is
stimulated by increased levels of prolactin
(pituitary) and human placental lactogen (from the
placenta) during pregnancy.
• Milk release from alveolar cells is inhibited by the
high levels of progesterone and estrogen during
pregnancy.
• Estrogen and progesterone also act with prolactin
to increase alveolar duct growth during pregnancy.
Lactation: Lactogenesis
• Lactogenesis: secretion of milk from alveolar
cells into the alveoli of the breast.
• Stimulated by prolactin, and occurs after
parturition when estradiol and progesterone levels
are decreased.
Lactation: Galactopoiesis and Milk Ejection
• Galactopoiesis: the maintenance of established
milk production, caused by prolactin.
• Milk Ejection: movement of milk from alveolar
ducts into the main duct system and out of the
breast. Induced by oxytocin.
Oxytocin causes contraction of myoepithelial
cells in the breast, causing milk release.
Regulation of Oxytocin and Prolactin
During Lactation
• There is a positive feedback effect of
breastfeeding on the production of oxytocin and
prolactin.
• Oxytocin levels increase due to suckling of the
breast by the infant. In addition, sight, sound, or
thought of the infant can also increase oxytocin
levels, causing milk ejection.
• Prolactin release is also increased by suckling of
the breast by the infant (but not by audiovisual
stimuli). Associated with suppression of
dopamine release.
Hormonal Induction of Labor
Estrogen
From ovaries
Induces oxytocin
receptors on uterus
Baby in utero
Oxytocin
(+)
From fetus and
mother’s post pit
Positive
feedbac
k
Stim uterus to
contract
Stim placenta to
make PGs
(+)
Stim more vigorous
contractions of uterus
Physical/emotional stress
(+)
Milk Letdown Reflex
Suckling stim pressure
receptors, which lead to
efferents to mother’s
hypothalamus
(+) Feedback cycle
continues till suckling
stops.
Hypo  Pit  oxytocin  stim
breast myoepithelial cells to contract
Alveolar glands
respond by releasing
milk