Learning objectives
• Name the key hormones secreted by graffian
follicles and corpora lutea of the ovaries.
• Describe the physiologic changes that occur in
the female reproductive organs during the
ovarian and menstrual cycle.
• Know the general actions of 17-estradiol and
progesterone.
hundred thousand
• When a female child is born, each ovum is
surrounded by a single layer of granulosa cells;
the ovum, with this granulosa cell sheath, is
called a primordial follicle,
• Throughout childhood, the granulosa cells are
believed to provide nourishment for the ovum
and to secrete an oocyte maturation-inhibiting
factor that keeps the ovum suspended in its
primordial state in the prophase stage of meiotic
division.
• Then, after puberty, when FSH and LH from the
anterior pituitary gland begin to be secreted in
significant quantities, the ovaries, together with
some of the follicles within them, begin to grow.
FSH is decreasing because of the
inhibitory effect of estrogen on
FSH release.
Peripher
al
Actions
estrogen
increases their
proliferation and
sensitivity to FSH.
Peripheral effects of estrogen produced by the
granulosa cells during the follicular phase include
• Circulating estrogens stimulate the female sex
accessory organs and sec-ondary sex
characteristics.
• Rising levels of estrogens cause the endometrial
cells of the uterine mucosal layers to increase
their rate of mitotic division (proliferate).
• Circulating estrogens cause the cervical mucus to
be thin and watery, making the cervix easy for
sperm to traverse
5-10
developing
follicle
progesterone
LH
Proliferative Phase (Estrogen Phase) of the
Endometrial Cycle, Occurring Before Ovulation
• The endometrial surface is re epithelialized
• Endometrium increases greatly in thickness, owing to
increasing numbers of stromal cells and to
progressive growth of the endometrial glands and
new blood vessels into the endometrium.
• The endometrial glands, especially those of the
cervical region, secrete a thin, stringy mucus.
2 days prior to ovulation
estrogen
begins to
fall about 1
day before
ovulation
Estrogen
FSH
LH removes the
restraint upon
meiosis, which has
been arrested
in prophase for
years. The first
meiotic division is
completed, and the
first polar
body is extruded
2 days
Corpus Luteum
• The process of luteinization occurs following
the exit of the oocyte from the follicle.
• The corpus luteum is made up of the
remaining granulose cells, thecal cells, and
supportive tissue.
• Once formed, the luteal cells are stimulated
by LH to secrete considerable progesterone
and some estrogen. Progesterone inhibits LH
secretion (negative feedback).
The increased plasma level of progesterone
has several actions
• It causes the uterine endometrium to become
secretory, providing a source of nutrients for
the blastocyst.
• It causes the cervical mucus to become thick,
sealing off the uterus from further entry of
sperm or bacteria.
• It has thermogenic properties, causing the
basal body temperature to increase by 0.5–
1.0° F.
Secretory Phase (Progestational Phase) of the
Endometrial Cycle, Occurring After Ovulation
• Progesterone causes marked swelling and secretory
development of the endometrium.
• The glands increase in tortuosity; an excess of
secretory substances accumulates in the glandular
epithelial cells.
• Also, the cytoplasm of the stromal cells increases; lipid
and glycogen deposits increase greatly in the stromal
cells;
• Blood supply to the endometrium further increases in
proportion to the developing secretory activity.
• Length of the secretory phase is constant – 14 days
Involution of the Corpus Luteum and
Onset of the Next Ovarian
Cycle
• Estrogen and progesterone, secreted by the
corpus luteum during the luteal phase of the
ovarian cycle, have strong feedback effects on
the anterior pituitary gland to maintain low
secretory rates of both FSH and LH.
• The lutein cells secrete small amounts of the
hormone inhibin, inhibits secretion by the
anterior pituitary gland, especially FSH
secretion
Final involution
• Occurs at the end of almost exactly 12 days of
corpus luteum life.
• At this time, the sudden cessation of secretion
of estrogen, progesterone, and inhibin by the
corpus luteum removes the feedback
inhibition of the anterior pituitary gland,
allowing it to begin secreting increasing
amounts of FSH and LH again.
Monthly endometrial cycle and
mensuration
(1) proliferation of the uterine endometrium;
(2) development of secretory changes in the
endometrium
(3) desquamation of the endometrium, which is
known as menstruation
Proliferative Phase (Estrogen Phase) of the
Endometrial Cycle, Occurring Before Ovulation
• The endometrial surface is re epithelialized
• Endometrium increases greatly in thickness, owing to
increasing numbers of stromal cells and to
progressive growth of the endometrial glands and
new blood vessels into the endometrium.
• The endometrial glands, especially those of the
cervical region, secrete a thin, stringy mucus.
Secretory Phase (Progestational Phase) of the
Endometrial Cycle, Occurring After Ovulation
• Progesterone causes marked swelling and secretory
development of the endometrium.
• The glands increase in tortuosity; an excess of
secretory substances accumulates in the glandular
epithelial cells.
• Also, the cytoplasm of the stromal cells increases; lipid
and glycogen deposits increase greatly in the stromal
cells;
• Blood supply to the endometrium further increases in
proportion to the developing secretory activity.
• Length of the secretory phase is constant – 14 days
Monitoring the Menstrual Cycle
The amount of sex steroids excreted in the urine
can be used to monitor the menstrual cycle. For
example:
• Low progesterone metabolites and low but
slowly rising estrogen metabo-lites characterize
the early follicular phase.
• Low progesterone metabolites and rapidly rising
estrogen metabolites characterize the latter part
of the follicular phase just before ovulation.
• Elevated levels of progesterone metabolites
characterize the luteal phase and pregnancy. In
the early luteal phase progesterone is rising, in
the latter half it is falling.
pathological
• Anatomic abnormalities
• A hypothalamic–pituitary origini. Kallman’s syndrome,
ii. Functional hypothalamic amenorrhea,
iii. Amenorrhea in female athletes,
iv. Eating disorders,
v. Hypothyroidism, and
vi. Pituitary tumors such as prolactinomas.
• Ovarian causes –
i. Premature ovarian failure (premature meno-pause),
ii. Repetitive ovulation failure, or
iii. Anovulation (intermittent bleeding),
iv. Polycystic ovary.
Polycystic Ovarian Syndrome
• One theory suggests that it originates as an
exaggerated adrenarche in obese girls.
• The high extraglandular estrogens (mainly
estrone) selectively suppress FSH. Ovarian
follicles do have a suppressed aromatase activity
and thus a diminished capacity to convert
androgen into estrogen, but the adrenals may
also contribute to the excess androgens as well.
• High androgens promote atresia in developing
follicles and disrupt feedback relationships.
Polycystic Ovarian Syndrome
• The overall result is anovulation-induced
amenorrhea with an estrogen-induced
endometrial hyperplasia and breakthrough
bleeding.
• Characterized by infertility, hirsutism, obesity,
insulin resistance, and amenorrhea or
oligomenorrhea
Hirsutism
• Defined as an excessive generally male pattern of hair
growth.
• Virilization refers to accompanying additional alterations,
such as deepening of the voice, clitoromegaly, increased
muscle bulk, and breast atrophy.
• It is often associated with conditions of androgen excess
such as con-genital adrenal hyperplasia and polycystic
ovarian syndrome.
• Axillary and pubic hair are sensitive to low levels of
androgen.
Hair on the upper chest, face (scalp region not involved), and
back requires more androgen and represents the pattern seen
in males.
Hirsutism
• Circulating androgens involved are
testosterone, DHEA, DHEAS, and
androstenedione in response to LH and ACTH.
• Measurements of DHEAS as well as a
dexamethasone suppression test helps in
separating an adrenal from an ovarian source.
• Polycystic ovarian syndrome is the most
common cause of ovarian androgen excess
Menopause
• At age 40 to 50 years, the sexual cycle usually
becomes irregular, and ovulation often fails to
occur.
• At about age 45 years, only a few primordial
follicles remain to be stimulated by FSH and
LH, the production of estrogens by the ovaries
decreases as the number of primordial
follicles approaches zero.
• When estrogen production falls below a
critical value, the estrogens can no longer
inhibit the production of the gonadotropins
FSH and LH.
• FSH and LH ,are produced after menopause in
large and continuous quantities.
physiological changes
(1) “hot flushes”
(2) psychic sensations of dyspnea
(3) irritability,
(4) fatigue,
(5) anxiety,
(6) occasionally various psychotic states,
(7)decreased strength and decreased
calcification of bones throughout the body.
Female hormones
Functions of the Estrogens—
Their Effects on the Primary and
Secondary Female Sex
Characteristics
1. Effect of Estrogens on the Uterus and External
Female Sex Organs.
• The ovaries, fallopian tubes, uterus, and vagina all
increase several times in size. Also, the external
genitalia enlarge, with deposition of fat.
• change the vaginal epithelium from a cuboidal
into a stratified type
• marked proliferation of the endometrial stroma
and greatly increased development of the
endometrial glands,
2. Effect of Estrogens on the Fallopian Tubes
3. Effect of Estrogens on the Breasts.
 (1) development of the stromal tissues of the breasts,
 (2) growth of an extensive ductile system, and
 (3) deposition of fat in the breasts
4. Effect of Estrogens on the Skeleton
 inhibit osteoclastic activity in the bones
 unite the epiphyses with the shafts of the long bones
5. Effect of Estrogens on Protein Deposition
slight positive nitrogen balance
6. Effect of Estrogens on Body Metabolism and
Fat Deposition.



increase the whole-body metabolic rate
fat in the subcutaneous tissues
deposition of fat in the buttocks and thighs
7. Effect of Estrogens on the Skin.
Soft, smooth vascular
8. Effect of Estrogens on Electrolyte Balance
sodium and water retention by the kidney tubules
Relative levels of LH release in human females
throughout life.
During the first few years after menopause, follicles
timulating hormone (FSH) levels are normally
extremely high. A 56-year-old woman completed
menopause 3 years ago. However, she is found to
have low levels of FSH in her blood. Which of the
following is the best explanation for this finding?
A) She has been receiving hormone replacement
therapy
with estrogen and progesterone since she completed
menopause
B) Her adrenal glands continue to produce estrogen
C) Her ovaries continue to secrete estrogen
D) She took birth control pills for 20 years before
menopause
A female athlete who took testosterone-like steroids for
several months stopped having normal menstrual cycles.
What is the best explanation for this observation?
A) Testosterone stimulates inhibin production from
the corpus luteum
B) Testosterone binds to receptors in the endometrium,
resulting in the endometrium’s failure to develop during the
normal cycle
C) Testosterone binds to receptors in the anterior
pituitary that stimulate the secretion of folliclestimulating
hormone (FSH) and luteinizing hormone (LH)
D) Testosterone inhibits the hypothalamic secretion
of gonadotropin-releasing hormone and the pituitary
secretion of LH and FSH
Seven days after ovulation, pituitary secretion of
luteinizing hormone (LH) decreases rapidly. What is the
cause of this decrease in secretion?
A) The anterior pituitary gland becomes unresponsive
to the stimulatory effect of gonadotropin-releasing
hormone (GnRH)
B) Estrogen from the developing follicles exerts a
feedback inhibition on the hypothalamus
C) The rise in body temperature inhibits hypothalamic
release of GnRH
D) Secretion of estrogen and progesterone by the corpus
luteum suppresses hypothalamic secretion of GnRH
and pituitary secretion of LH
E) None of the above
A young woman is given daily injections of a substance
beginning on the 16th day of her normal menstrual
cycle and continuing for 3 weeks. As long as the
injections continue, she does not menstruate. The
injected substance could be which of the following?
A) Testosterone
B) FSH
C) An inhibitor of progesterone’s actions
D) A prostaglandin E2 inhibitor
E) HCG
During the 12-hr period preceding ovulation, which of
the following is true?
A) The plasma concentration of estrogen is rising
B) A surge of luteinizing hormone is secreted from
the pituitary
C) The surge occurs immediately after the formation
of the corpus luteum
D) The surge is followed immediately by a fall in the
plasma concentration of progesterone
E) The number of developing follicles is increasing
When do progesterone levels rise to their highest
point during the female hormonal cycle?
A) Between ovulation and the beginning of
menstruation
B) Immediately before ovulation
C) When the blood concentration of luteinizing
hormone is at its highest point
D) When 12 primary follicles are developing to the
antral stage
As menstruation ends estrogen levels in the
blood rise rapidly. What is the source of the
estrogen?
A) Corpus luteum
B) Developing follicles
C) Endometrium
D) Stromal cells of the ovaries
E) Anterior pituitary gland
If a woman has a tumor secreting large amounts
of estrogen from the adrenal gland, which of
the following will occur?
A) Progesterone levels in the blood will be very
low
B) Her luteinizing hormone secretion rate will be
totally suppressed
C) She will not have normal menstrual cycles
D) Her bones will be normally calcified
E) All of the above
A 20-year-old woman is not having menstrual cycles.
Her plasma progesterone concentration is found to be
minimal. What is the explanation for the low level of
progesterone?
A) LH secretion rate is elevated
B) LH secretion rate is suppressed
C) FSH secretion rate is suppressed
D) No corpus luteum is present
E) High inhibin concentration in the plasma has
suppressed progesterone synthesis
Before the preovulatory surge in luteinizing
hormone, granulosa cells of the follicle secrete
which of the following?
A) Testosterone
B) Progesterone
C) Estrogen
D) Inhibin
Two days before the onset of menstruation, secretions
of follicle-stimulating hormone (FSH) and luteinizing
hormone (LH) reach their lowest levels.
What is the cause of this low level of secretion?
A) The anterior pituitary gland becomes unresponsive
to the stimulatory effect of gonadotropinreleasing
hormone (GnRH)
B) Estrogen from the developing follicles exerts a
feedback inhibition on the hypothalamus
C) The rise in body temperature inhibits hypothalamic
release of GnRH
D) Secretion of estrogen, progesterone, and inhibin
by the corpus luteum suppresses hypothalamic
secretion of GnRH and pituitary secretion of FSH
What is the cause of menopause?
A) Reduced levels of gonadotropic hormones
secreted
from the anterior pituitary gland
B) Reduced responsiveness of the follicles to the
stimulatory effects of gonadotropic hormones
C) Reduced rate of secretion of progesterone
from the corpus luteum
D) Reduced numbers of follicles available in the
ovary for stimulation by gonadotropic hormones