Lecture 54
Endocrine Functions
of the Ovary
Dr. Khaled Khalil
By the end of this session, the student should:
 Identify different sex hormones secreted by ovary and contrast
their biological activity.
 Describe the target cells and physiological actions of estrogen
including puberty.
 Describe the target organs and physiological actions of
progesterone.
 Summarize the interplay between hypothalamic, pituitary and
ovarian hormones and their cyclic changes as the key regulator of
female monthly rhythm.
 Correlate this knowledge to pathogenesis female infertility and
menopause.
Guyton & Hall Textbook of Medical Physiology – 12th ed. – P. 987–988 & 996-997
II- Female reproductive System
The female reproductive system consists of:
A) The Ovaries (female gonads)
 The ovaries are the primary sex organs in females
 They have two functions:
1- Oogenesis: formation of ova.
2- Steroidogenesis: synthesis and secretion of the female sex
hormones .
B) The secondary sex organs
 They include the vagina, uterus, two fallopian tubes, external
genitalia and the mammary glands.
Hormonal changes during female sexual cycle:
1- Estradiol:
- In the preovulatory phase, it is secreted in large amounts by the
growing ovarian follicles under the influence of FSH.
- Two days before ovulation, estrogen secretion by the graafian follicle
is markedly increased.
- In the postovulatory phase, the plasma estrogen level is initially low
due to rupture of the Graafian follice. After formation of the corpus
luteum, estrogen secretion increases, but it decreases two days before
the end of the cycle due to degeneration of the corpus luteum.
2- Progesterone:
- In the preovulatory phase, small amounts of progesterone are
secreted by the ovarian follicles which secrete mainly estrogens.
- In the postovulatory phase, the hormone is secreted by the corpus
luteum in an increasing rate that reaches the peak by the 22nd day of
the cycle. The rate of secretion is markedly lowered two days before
the end of the cycle due to degeneration of the corpus luteum.
3- Follicel-stimulating hormone (FSH):
- In the pre-ovulatory phase, the rate of FSH secretion is high in
the beginning of the phase because the plasma estrogen level is low,
thereafter; it decreases to a low level due to the negative feedback
effect of the high plasma estrogen level.
- Two days before ovulation, the secretion of FSH is increased by 23 folds due to the positive feedback effect of the high estrogen level
on the anterior pituitary.
- In the postovulatory phase, the rate of FSH secretion is lowered
because of the high estrogen level secreted by the corpus luteum.
4- Luteinizing hormone (LH):
- In the preovulatory phase, the rate of LH secretion from the anterior
pituitary is constant (basal).
- Two days before ovulation, the rate of LH secretion is increased by 610 folds (LH surge) due to the positive feedback effect of the high
estrogen level on the anterior pituitary.
- In the post ovulatory phase, LH secretion is inhibited by the negative
feedback effect of the high progesterone level secreted by the corpus
luteum.
Functions of FSH:
1- Stimulation of early growth of ovarian follicles.
2- With LH --------> maturation of graafian follicles.
3- Stimulates estrogen secretion by granulosa cells of growing
follicles due to stimulation of aromatase enzyme.
Functions of LH:
1- Regulates estrogen secretion from theca interna &
granulosa cells of graafian follicles.
2- LH surge ------> ovulation & formation of corpus luteum.
3- Stimulates secretion of estrogen & progesterone from
corpus luteum.
Gonadotropin-releasing hormone (GnRH)
- Secreted by hypothalamus into the hypothalamo-hypophyseal
portal circulation.
- Stimulate secretion of both LH & FSH from anterior pituitary
gland.
- Secreted in pulses by GnRH pulse generator in the median basal
hypothalamus each 1-2 hours which lasts 5-25 minutes.
- Pulse frequency is increased by estrogen & decreased by
progesterone.
 In preovulatory, frequency increases.
 At ovulation, the sensitivity of gonadotrops to GnRH
increases due to their exposure to high frequency pulses.
 In postovulatory, frequency decreases.
Estrogens
Sources:
 In non-pregnant female, estrogens are secreted mainly by:
1) the ovaries (theca interna of ovarian follicles & lutein cells of corpus
luteum), granulosa cells into the follicular fluid, and stromal tissue of the
ovary.
2) Minute amounts are secreted by the adrenal cortex.
 In pregnancy, large quantities are secreted by the placenta.
Types:
These are 17-β oestradiol, oestrone, and oestriol
1- β oestradiol is the principal one, being 12 times as potent as estrone
and 80 times that of estriol. It is secreted by the ovaries.
2- oestrone:
a) Small amounts are secreted by the ovaries.
b) Most of it is formed in the peripheral tissues from androgens secreted
by adrenal cortices and ovarian theca cells.
3- Oestriol: oxidative product of oestradiol & oestrone which occurs in the
liver.
Functions:
1- On ovaries:
a) Stimulate growth of ovarian follicles.
b) By inducing LH surge ------> ovulation & corpus luteum formation.
2- On 2ry sex organs:
a) Uterus:
i. Stimulates proliferative phase of menstrual cycle (endometrium).
ii. Myometrium: ↑ sensitivity of myometrium to the action of oxytocin, ↑
uterine blood flow, ↑ excitability , ↑ contractile proteins.
b) Cervix: they ↑ the amount & ↓ viscosity of cervical mucus which is
characerized by ferning & Spinnbarkeit. .
c) Vagina:
i. Stratification of epithelium which is more resistant to trauma &
infection.
ii. ↑ vascularity of the wall.
iii. Deposition of glycogen -- lactic acid -- acidity of the vagina.
d) Fallopian tubes:
i. ↑ motility.
ii. ↑ number and activity of cilia.
which helps transport of the fertilized ovum into the uterus.
e) Breasts:
i. Deposition of fat at puberty.
Ii. Formation of duct system & nipples.
iii. ↑ vascularity.
Iv. Pigmentation of areola.
3- On female sex characters:
a) Feminine distribution of fat in breasts, lower abdomen, buttoks,
thigh, mons pubis & labia majora.
b) ↑ vascularity of the skin which is soft & smooth.
c) ↑ libido & psychological make up of female.
4- Metabolic Effects:
a) Slight protein anabolic effects.
b) Estrogens inhibit osteoclastic activity in the bones and therefore
stimulate bone growth. This effect is due to stimulation of
osteoprotegerin, also called osteoclastogenesis inhibitory factor, a
cytokine that inhibits bone resorption. Then union of epiphysis.
c) ↓ cholesterol.
d) Retention of Na, H2O, Ca, phosphate.
5- On endocrine glands:
a) ↑ size of pituitary.
b) ↑ secretion of angiotensinogen.
c) ↑ thyroxin-binding globulin and transcortin.
d) Regulate the secretion of pituitary gonadotropins.
Progestins
Sources & Types:
These are steroid female sex hormones C21. They include mainly:
1- Progesterone, which is secreted by:
a) Corpus luteum.
b) Small amounts by ovarian follicles and suprarenal cortex.
c) In pregnancy, considerable amounts are secreted by the placenta.
2- 17 α-hydroxyprogesterone, which is released along with estrogen by the
growing Graafian follicles.
Functions:
1- On uterus:
a) It induces the secretory phase of the menstrual cycle.
b) It has antiestrogenic effects which lead to:
i. ↓ sensitivity of myometrial cells to oxytocin.
ii. ↑ number of estrogen receptors in the endometrium.
iii. ↑ rate of conversion of β-estradiol to less active estrogens.
c) In pregnancy:
i. Is essential for formation of the placenta and embedding of the
fertilized ovum.
ii. Prevents abortion by inhibiting uterine contractions due to its
antiestrogenic effects.
iii. It suppresses the ovarian cycles probably by inhibiting the release
of pituitary GTHs.
2- On cervix: ↓ amount & ↑ viscosity of its mucus.
3- On vagina:
a) Thick mucus.
b) Epithelium proliferates and becomes infiltered with leukocytes.
4- Fallopian tubes: ↑ secretion for the nutrition of the fertilized ovum
5- Mammary glands: Prepares them for lactation by promoting growth of
secretory alveoli & lobules.
6- Thermogenic effect.
7- Natriuretic effect by antialdosterone effect.
8- Inhibition of ovulation.
Menopause
 Cessation of menstruation due to aging (at 40-50 ys of age).
 Causes:
1- Burning out of ovarian follicles.
2- Aging of the remaining follicles.
 Manifestations: (loss of estrogen)
1- Hot flushes.
2- Anxiety and fatigue.
3- Atrophy of ovaries.
4- Atrophy of 2ry sex organs except the clitoris.
5- Osteoporosis & muscle wasting.
 Treatment:
By local & systemic estrogen.
Ovarian Dysfunction
1- Hypogonadism:
a) Primary due to:
-Congenital abnormalities of ovaries.
- Surgical removal.
- Destruction by diseases, toxins, or x-ray.
b) Secondary due to failure of GT secretion. It may be of pituitary or
hypothalamic origin.
Manifestations:
A) Before puberty:
1- 1ry amenorrhea and sterility.
2- 2ry sex organs fail to develop.
3- Loss of sexual desire and homosexuality.
4- Delayed union of epiphyseal cartilages - tall
5- Absence of feminine distribution of fat.
6- ↓ BMR.
B) After puberty:
1- 2ry amenorrhea and sterility.
2- Atrophy of endometrium, vaginal mucosa and breasts.
3- Osteoporosis & muscle wasting.
4- Psychological and vasomotor disturbance.
2- Hyperfunction:
This is usually due to ovarian tumours.
 Manifestations:
a) Before puberty: precocious puberty.
b) After puberty: polymenorrhea & menorrhagia.
c) After menopause: Irregular uterine bleeding after stoppage of menstruation