Lecture 5
Hormonal control of Reproduction
Physiology of hormone
2007
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Homeostasis of reproduction depending
on physiological levels of the following
hormones
„
GnH-RH
LH
„
Gonadotropin stimulating hormones
FSH
Sex hormones( Testosterone, Progesterone,E2).
Prolactine, inhibin, activin, follastin, Cytokines,
Insuline, melatonin Thyroid hormones and
leptin.
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Sexual Determination
„
„
„
„
Each zygote inherits 23 chromosomes from the
mother and 23 chromosomes from the father.
Produce 23 pairs of homologous chromosomes.
„ First 22 pairs of chromosomes are autosomal
chromosomes.
rd pair are sex chromosomes.
„ 23
Diploid cell undergoes meiotic division, its daughter
cells receive only 1 chromosome from each
homologous pair.
„ The gametes are haploid.
Chromosomal gender of zygote determined by
fertilizing sperm.
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Formation of
of Testes
Testes
Formation
„
„
„
„
„
First 40 days after conception the gonads of
males and females are similar in appearance.
In the present of chromosome Y:
H-Y antigen will release.
Mllerian regression factor.
Testis-determining factor (TDF) promotes the
conversion to testes:
„
Seminiferous tubules appear within 43-50 days
following conception.
„
Produce:
„
„
„
Germinal cells: sperm.
Nongerminal cells: Sertoli cells.
Leydig cells:
„
Appear about day 65.
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Formation of Testes
„
Leydig cells secrete testosterone.
„
„
Begins at the 8th week and peaks at 1214th week.
Masculinizes embryonic structures.
„
„
(continued)
[Testosterone] then declines to very low levels
until puberty.
Testes descend into scrotum shortly
before birth.
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Formation of Ovaries
„
„
Absence of Y chromosome and TDF,
female develop ovaries.
Ovarian follicles do not appear until 2nd
trimester, about day 105.
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Chromosomal Sex and Development
of Embryonic Gonads
Insert fig. 20.4
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Endocrine Regulation of
Reproduction
„
„
Hypothalamus releases LHRH (GnRH) into
hypothalamo-hypophyseal portal vessels.
Anterior pituitary secretes:
„
„
„
LH (luteinizing hormone).
FSH (follicle-stimulating hormone).
Secreted in pulsatile fashion to prevent
desensitization and down regulation of
receptors.
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Endocrine Interactions
„
„
Anterior pituitary secretes LH and FSH.
Secretion of LH and FSH stimulated by LHRH
(GNRH).
„
Primary effects of LH and FSH on gonads:
„
„
„
Stimulation of spermatogenesis and oogenesis.
Stimulation of gonadal hormone secretion.
Maintenance of gonadal structure.
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Endocrine Regulation
„
Negative feedback:
„
„
Inhibits GnRH from
hypothalamus.
Inhibits anterior
pituitary response to
GnRH.
„
„
Female:
„
„
Inhibin secretion
inhibits anterior
pituitary release of
FSH.
Estrogen and
progesterone.
Male:
„
Testosterone.
Insert fig. 20.9
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Onset of Puberty
„
„
FSH and LH secretion is high in
newborn, but falls to low levels in few
weeks.
At puberty:
„
„
„
Brain maturation increases GnRH secretion.
Decreased sensitivity of gonadotropin to
negative feedback.
During late puberty, pulsatile secretion
of LH and FSH increase during sleep.
„
Stimulate a rise in sex steroid secretion.
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Onset of Puberty
„
Stimulates rise in
testosterone and
estradiol-17β.
„
„
„
Produce secondary
sexual characteristics.
Age of onset related to
the % of body fat and
physical activity in the
female
Leptin secretion from
adipocytes may be
required for puberty.
(continued)
Insert fig. 20.10
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Pineal Gland
„
„
Secretes melatonin.
Stimulated by postganglionic
sympathetic neurons.
„
Activity of these neurons is inhibited by
nerve tracts that are activated by light.
„
„
„
Secretion influenced by light-dark cycles.
Inhibits gonadotropin secretion.
Role in humans not established.
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Male Reproductive System
„
Testes:
„
Seminiferous
tubules:
„
„
„
Contain receptor
proteins for FSH
in Sertoli cells.
FSH stimulates
spermatogenesis
to occur.
Leydig cells:
„
„
LH stimulates
secretion of
testosterone.
Contain receptor
proteins for LH.
Insert fig. 20.12
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Control of LH and FSH Secretion
„
Negative feedback:
„
Testosterone inhibits LH
and GnRH production.
„
Maintain relatively constant
secretion of LH and FSH.
„
„
„
„
Declines gradually in men
over 50 years of age.
Testosterone converted to
DHT, which inhibits LH.
Inhibin inhibits FSH
secretion.
Aromatization reaction
producing estradiol in
the brain, is required
for the negative
feedback effects.
Insert fig. 20.13
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Endocrine Function of the Testes
„
Testosterone and its
derivatives are
responsible for initiation
and maintenance of
body changes in
puberty.
„
„
„
Stimulate growth of
muscles, larynx, and bone
growth until sealing of the
epiphyseal discs.
Promote hemoglobin
synthesis.
Act in paracrine fashion,
responsible for
spermatogenesis.
Insert fig. 20.15
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Estrogen Secretion
„
Sertoli and Leydig cells secrete small
amounts of estradiol.
„
„
Receptors found in Sertoli and Leydig cells
and accessory organs.
May be responsible for:
„ Negative feedback in brain.
„ Sealing of epiphyseal plates.
„ Regulatory function in fertility.
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Spermatogenesis
„
Spermatogonia:
„
„
Replicate initially by
mitosis.
One of the 2
primary
spermatocytes
undergoes
meiosis:
„
2 nuclear divisions:
„
„
1st meiotic division
produces 2
secondary
spermatocytes.
2nd meiotic
division produces
4 spermatids.
Insert 20.16
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Spermiogenesis
„
„
Maturation of
spermatozoa.
Phagocytosis of
cytoplasm by
the Sertoli cells.
„
Cytoplasm is
eliminated.
Insert fig. 20.18
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Sertoli Cells
„
Form blood-testes barrier:
„
„
„
„
Secrete inhibin.
Phagocytize residual bodies:
„
„
Prevents autoimmune destruction of sperm.
Produce FAS ligand which binds to the FAS receptor on surface
to T lymphocytes, triggering apoptosis of T lymphocytes.
„ Prevents immune attack.
May transmit information molecules from germ cells to Sertoli
cells.
Secrete androgen-binding protein (ABP):
„
Binds to testosterone and concentrates testosterone in the
tubules.
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Hormonal Control of
Spermatogenesis
„
Formation of primary spermatocytes
and entry into early prophase I, begin
during embryonic development.
„
„
„
Testosterone required for completion
of meiosis and spermatid maturation.
Secrete paracrine regulators:
„
„
„
„
Spermatogenesis arrested until puberty.
IGF-1.
Inhibin.
Transforming growth factor.
FSH necessary in the later stages of
spermatid maturation.
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Male Accessory Organs
„
Epididymis responsible for:
„
„
„
„
Ductus (vas) deferens:
„
„
Carries sperm from epididymis into pelvic cavity.
Seminal vesicles secrete:
„
„
Maturational changes.
Resistance to pH changes and temperature.
Storage of sperm between ejaculations.
Fructose.
Prostate secretes:
„
„
„
„
Alkaline fluid.
Citric acid.
Ca2+.
Coagulation proteins.
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Erection, Emission, and
Ejaculation
„
Erection:
„
Controlled by hypothalamus and spinal cord.
„
„
„
Parasympathetic nervous system.
„
Blood flow into the erectile tissues of the penis.
Emission:
„
Movement of semen into the urethra.
„
„
Increased vasodilation of arterioles.
Stimulated by sympathetic nervous system.
Ejaculation:
„
Forcible expulsion of semen from the urethra out of the penis.
„
Stimulated by sympathetic nervous system.
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Male Fertility
„
„
60-150 million sperm/ml ejaculate.
Oligospermia:
„
„
„
Sperm count of < 20 million/ml ejaculate.
Decreased fertility caused by heat, pharmaceuticals, and illicit
drugs.
Male contraception:
„
Compounds that suppress gonadotropin secretion.
„
„
„
Testosterone.
Progesterone and GnRH antagonist.
Vasectomy:
„
Each ductus deferens is cut and tied.
„
„
Interferes with sperm transport.
May develop anti-sperm antibodies.
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Female Reproductive System
„
Ovaries:
„
Contain a large number of follicles which
enclose ova.
„
„
„
Extensions called fimbriae partially cover each
ovary.
At ovulation, secondary oocyte is extruded.
Fallopian (uterine) tubes:
„
Ova drawn into the tubes by cilia.
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Female Reproductive System
(continued)
„
Uterus:
„
Has 3 layers:
„
Perimetrium:
„
„
Myometrium:
„
„
Smooth muscle layer.
Endometrium:
„
„
Outer layer of connective tissue.
Inner layer of stratified, squamous, nonkeratinized
epithelium.
„ Shed during menstruation.
Vagina:
„
Cervical mucus plug.
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Ovarian Cycle
„
„
„
5 mo. gestation,
ovaries contain 6-7
million oogonia.
Oogenesis arrested in
prophase of 1st
meiotic division
(primary oocyte).
Apoptosis occurs:
„
„
„
2 million primary oocytes
at birth.
400,000 primary oocytes
at puberty.
400 oocytes ovulated
during the
reproductive years.
Insert fig. 20.30
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Ovarian Cycle
„
Primary oocytes are
contained in primary
follicles.
„
„
„
Develop into
secondary follicles.
Fusion of its vesicles
to form the antrum.
„
„
FSH stimulates
granulosa cell growth.
Mature graafian follicle.
1st meiotic division
completed (secondary
oocyte).
„
Polar body fragments.
(continued)
Insert fig. 20.32
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Ovarian Cycle
„
Secondary oocyte confined to graafian follicle.
„
„
(continued)
Arrested at metaphase II.
Under FSH stimulation:
„ Theca cells secrete testosterone.
„
Granulosa cells contain the enzyme aromatase
to convert testosterone into estrogen.
„
Granulosa cells form a ring (corona radiata) around
oocyte and form mound (cumullus oophorus).
„ Between oocyte and corona radiata is zona
pellucida.
„ Provides barrier to the sperm to fertilize the egg.
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Ovulation
„
One graafian follicle
forms bulge on
surface of ovary.
„
„
Extrudes secondary
oocyte into the
uterine tube.
LH causes the empty
follicle to become
corpus luteum which
secretes:
„
„
Progesterone and
estrogen.
If not fertilized,
becomes corpus
albicans.
Insert fig. 20.33
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Pituitary-Ovarian Axis
„
Hormonal interactions between the anterior
pituitary and the ovaries.
„
Anterior pituitary secretes FSH and LH.
„
„
„
„
Controlled by GnRH.
FSH secretion is slightly greater than LH
during early phase of menstrual cycle.
LH secretion greatly exceeds FSH secretion
just prior to ovulation.
- feedback.
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Menstrual Cycle
„
„
Menstruation:
Day 1-4/5.
„
Day 1 is the first day of menstruation.
„
„
Duration approximately 28 days.
Secretions of estrogen and
progesterone are at their lowest.
„
Ovaries contain only primary follicles.
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Follicular Phase
„
„
Lasts from day 1 to about 13.
FSH:
„
Follicles become increasingly sensitive to FSH.
„
„
Toward the end of the phase, sensitivity of
FSH receptors increases.
„
„
FSH stimulates the production of FSH receptors on the
granulosa cells.
FSH and estradiol stimulate production of LH
receptors in graafian follicle.
Rapid rise in estradiol from granulosa cells.
„ Negative feedback on LH and FSH.
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Follicular Phase
„
Hypothalamus increases frequency of GnRH
pulses.
„
„
(continued)
Augments the ability of anterior pituitary to
respond to GnRH, to increase LH secretion.
Positive feedback:
„ LH surge begins 24 hours before ovulation.
„
Triggers ovulation.
„
FSH increase stimulates development of new follicles.
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Endocrine Control of the Ovarian Cycle
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Ovulation
„
„
„
Wall of graafian
follicle ruptures.
Day 14.
1st meiotic
division is
completed.
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Luteal Phase
„
„
LH stimulates formation of the empty follicle
into corpus luteum.
Corpus luteum secretes:
„ Progesterone:
Plasma concentration rapidly rises.
Exerts negative feedback on LH and FSH.
„
„
„
Inhibin:
„
Suppresses FSH secretion.
„
Inhibin production decreases towards end of luteal
phase.
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Luteal Phase
„
„
(continued)
Corpus luteum regresses unless
fertilization occurs:
„ Estradiol decreases.
„ Progesterone decreases.
Withdrawal of estradiol and
progesterone cause menstruation to
occur.
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Cycle of Ovulation and Menstruation
Insert fig. 20.35
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Cyclic Changes in the
Endometrium
„
Proliferative Phase:
„
„
„
„
Ovary is in follicular phase.
Estradiol stimulates growth of
endometrium of stratum functionale.
Spiral arteries develop.
Estradiol:
„
Stimulate production of receptor proteins
for progesterone.
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Cyclic Changes in the
Endometrium
(continued)
„
Secretory phase:
„
„
„
„
Ovary is in luteal phase.
Progesterone stimulates development of
uterine glands, which become engorged
with glycogen.
Endometrium becomes thick, vascular, and
spongy.
Cervical mucus thickens and becomes
sticky.
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Cyclic Changes in the
Endometrium
(continued)
„
Menstrual phase:
„
„
„
Progesterone withdrawl causes constriction
of spiral arteries.
Necrosis and sloughing of endometrium
occurs.
Lasts 1-5 days.
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Contraceptive Methods
„
Contraceptive pill:
„
„
Negative feedback inhibits ovulation.
„
„
Synthetic estrogen combined with synthetic
progesterone pills are taken once each day for 3
weeks after the last day of menstruation.
Placebo pill taken the 4th week permits
menstruation.
Rhythm method:
„
Women measure oral basal body temperature
upon awakening daily.
„
On day of LH surge, there is a slight drop in basal body
temperature.
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Menopause
„
„
„
„
Cessation of ovarian activity and
menstruation.
Age ~ 50 years.
Ovaries are depleted of follicles.
Estradiol and inhibin withdrawl causes
hot flashes, and atrophy of the vaginal
wall.
„
LH and FSH increase.
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Fertilization
„
Ejaculation 300
million sperm, 100
reach (uterine)
fallopian tube.
„
Capacitation occurs.
„
„
Fertilization occurs
in the uterine tubes.
Acrosome of sperm
contains
hyaluronidase, an
enzyme that digests
a channel through
zona pellucida.
„
Sperm fuses with
ovum cell membrane.
Insert 20.39
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Fertilization
„
„
„
„
As fertilization
occurs, secondary
oocyte completes
2nd meiotic division.
Sperm enters ovum
cytoplasm.
Ovum nuclear
membrane
disappears, zygote
formed.
Centrosome of
zygote is derived
from sperm cell.
(continued)
Insert fig. 20.41
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Cleavage and Blastocyst
Formation
„
Cleavage:
„
„
„
30-36 hrs. after
fertilization, the zygote
divides by mitosis.
About 50-60 hours after
fertilization, the early
embryo develops into
morula.
Blastocyst develops:
„ Inner cell mass
„
„
Fetus.
Surrounding
chorion:
„
Trophoblasts form
placenta.
Insert fig. 20.43
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Implantation
„
„
6th day after
fertilization,
blastocyst attaches
to uterine wall.
Trophoblast cells
produce enzymes
that allow
blastocyst to
burrow into
endometrium.
Insert fig. 20.45
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Embryonic Stem Cells and
Cloning
„
Only fertilized egg cells and early cleavage cells are
totipotent:
„
„
Reproductive cloning:
„
„
Nucleus transplantation to produce stem cells for purpose of
growing specific tissue for the treatment of disease.
Pluripotent:
„
„
Adult stem cells can become totipotent if transplanted into
egg cell cytoplasm.
Therapeutic cloning:
„
„
Ability to create the entire organism.
Cells obtained from inner cell mass of blastocyst (embryonic
stem cells) can give rise to all tissues except the placenta.
Multipotent:
„
Can give rise to a number of differentiated cells.
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hCG (Human Chorionic
Gonadotropin)
„
Trophoblast cells
secrete hCG:
„
„
„
„
„
Signals corpus luteum
not to degenerate until
placenta secretes
adequate [hormones].
Prevents immunological
rejection of implanting
embryo.
Has thyroid-stimulating
ability.
Produces effects similar
to LH.
Basis of pregnancy test.
Insert fig. 20.46
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Placenta
„
„
Syncytiotrophoblast
secretes enzymes
that create blood
filled cavities in the
maternal tissue.
Cytotrophoblast then
forms villi that grow
into the pools of
venous blood.
„
„
Produces chorion
frondosum on the
side that faces the
uterine wall.
Other side of chorion
bulges into the
uterine cavity.
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Formation of the Placenta and
Amniotic Sac
„
Decidual reaction:
„
„
„
Decidua basalis:
„
„
„
Endometrial growth.
Accumulation of
glycogen.
Maternal tissue in contact
with the chorion
frondosum.
Decidua basalis and
chorion fondosum
together become
placenta.
Maternal and fetal blood
do not mix.
Insert fig. 20.50
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Amnion
„
„
Envelop the embryo
and umbilical cord.
Amniotic fluid
initially is isotonic,
but as fetus
develops;
concentration
changes by urine
and sloughed cells
of the fetus,
placenta, and
amniotic sac.
Insert fig. 20.48
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Placenta Function
„
„
Site for exchange of gases and other
molecules between maternal and fetal
blood.
Gas exchange:
„
„
„
„
02 and C02.
Nutrient exchange.
Waste exchange.
Synthesis of proteins and enzymes.
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Placental Hormones
„
hCS (chorionic somatomammotropin):
„
„
„
Actions similar to GH.
Actions similar to prolactin.
hCS and GH cause diabetic-like effect:
„ Glucose sparing effects by maternal
tissues.
„
Ensure sufficient supply of glucose for
placenta and fetus.
Polyuria.
„ Lipolysis.
„
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Placental Hormones
„
Fetal-placental unit:
„
„
(continued)
Placenta must cooperate with the adrenal
cortex in the fetus to produce estrogen.
Estrogen/estriol stimulates:
„
„
„
„
Endometrial growth.
Inhibition of prolactin secretion.
Growth of mammary ducts.
Enlargement of mother’s uterus.
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Placental Hormones
„
(continued)
Progesterone:
„
„
„
„
Suppresses uterine contractions.
Stimulates uterine growth.
Suppresses LH and FSH.
Stimulates development of alveolar tissue
of the mammary gland.
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Parturition
„
Estrogen in late pregnancy:
„
„
„
„
Stimulates production of oxytocin receptors
in myometrium.
Produces receptors for prostaglandins.
Produces gap junctions between
myometrium cells in uterus.
Factors responsible for initiation of labor
are incompletely understood.
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Parturition
(continued)
Insert fig. 20.52
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Parturition
„
Fetal adrenal cortex:
„
„
„
(continued)
Chain of events may be set in motion
through CRH production.
Fetal adrenal zone secretes DHEAS, which
travel from fetus and placenta.
Uterine contractions:
„
„
Oxytocin.
Prostaglandins.
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Lactation
„
„
Hypothalamus
releases PRH.
Anterior pituitary
releases prolactin:
„
„
„
Stimulates milk
production.
Prolactin secretion
primarily controlled
by PIH.
Oxytocin needed
for “milk letdown.”
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Lactation
„
Mammary gland:
„
Lobules contain glandular
alveoli that secrete milk
of the lactating female.
„
„
Alveoli secrete milk into
secondary tubule that
converge to form
mammary duct.
Ampulla:
„
„
(continued)
Where milk accumulates
during nursing.
Neuroendocrine reflex:
„
„
Act of nursing maintains
high levels of prolactin.
Sucking may cause
release of PRH.
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Milk-Ejection Reflex
Insert fig. 20.55