Physiology

of Reproduction
in Women

Cheng Biheng 程苾恒

M.D.
Dept. of Obstetrics&Gynecology
Renmin Hosp. of Wuhan Univ.
Cycle of Other Sites in Female Genitalia
 Cervical cycle
estrogen: thin/alkaline
progesterone:thick/tenacious/cellular
Cycle of Other Sites in Female Genitalia
Cycle of Other Sites in Female Genitalia
 Vaginal cycle
estrogen: epi-cornified/glycogens&acidity↑/ resistance ↑
progesterone: thick mucus/epi-proliferation
/leukocyte infiltration
 Cycle of Other Sites in Female Genitalia
 Breasts
 Estrogens: proliferation of mammary ducts
 Progesterone:
growth of lobules and alveoli;
breast swelling 、 tenderness and pain 10 days preceding me
nstruation caused by hyperemia and edema of interstitial tissu
e of the breast(disappear during menses)
Control of Menstrual Cycle
 HPOA

 HPOA(hypothalamus-pituitary-ovary axis)
an interal and concordant neuroendocrine system
between H&P: portal hypophysial vessels
(a group of blood vessels transmitting
substances directly from hypothalamus
to anterior pituitary)
 HPOA
 Hypothalamus:
Gonadotropin-releasing hormone (GnRH)
once called LH-RH
no single FSH-RH isolated
GnRH with functions of both
pulse interval: 60min(follicular phase);90~120min(luteal phase)
 long feedback: o→h
 short feedback: p→h
 ultrashort feedback: h→h
 Anterior pituitary:
Luteinizing hormone (LH)
follicle-stimulating hormone (FSH)
pulsed secretion
 Ovary:
Estrogens and progesterone
 HPOA

 GnRH: anterior pituitary→

LH&FSH synthesis↑;

receptor for GnRH ↑

 HPOA

 LH & FSH: ovary

FSH
theca cells:stroma cells differentiated into external and internal theca cells
and form LH receptors;
granulosa cells:cell proliferation; upregulating FSH-R;activating aromatas
e and estrogen↑;inducing LH-R; synthesis of IGF/IGF-R 、 inhibinA and acti
vins.
follicle recruitment
LH
theca cells: androgen↑
granulosa cells: luteinized and progesterone↑
preovulatory mature of oocyte(completing first meiosis)
facilitaing ovulation
sustain luteal function
 HPOA

 Progesterone:
endometrium/breasts
 Estrogen:
ovary/uterus/ breasts
 HPOA

 The hormones are secreted at different rate during different time

in a menstrual cycle.
 Ovarian Hormones

 Ovarian hormone synthesis

steroid hormones
common structure: cyclopentanoperhydrophenanthrene

21-Carbon: progesterone
19-Carbon: androgens
18-Carbon: estradiol>estrone>estriol
 Ovarian Hormones

 Ovarian hormone synthesis

 theca cells take in serum cholesterol in the form of LDL(low density lip
oprotein)
 cholesterol→pregnenolone(catalyzed by desmolase,LH via cyclic AMP)
 pregnenolone →androstenedione in 2 routes
Δ4: progesterone and 17α-hydroxyprogesterone
Δ5: 17α-hydroxypregnelonone and dehydroepiandrosterone(DHEA)
follicular phase: Δ5
luteal phase: Δ4 and Δ5
 androstenedione →estrone(catalyzed by aromatase,FSH via cyclic AM
P)
 testosterone →estradiol(catalyzed by aromatase,FSH via cyclic AMP)
 Ovarian Hormones
Cholesterol

Δ5 Pregnelonone Δ4
17α-Hydroxy-p
Progesterone
regnelonone

Dehydroepi-a 17α-Hydroxy-p
ndrosterone rogesterone

Androstenedione

Testosterone Estrone

Estradiol
 Ovarian Hormones
 Synthesis of estrogen
2 cell-2 gonadotropin hypothesis(Falck,1959)
 estrogens are synthesized by theca cells and granulosa cells under the coo
perative influence from LH and FSH.
 LH combines with LH-R on theca cells, changing cholesterol into A2 and
T;
 A2 and T enter the granulosa cells;
 FSH combines with its receptors on granulosa cells, changing A2 and T int
o E1 and E2
 Ovarian Hormones

Androstenedione

Theca
Cells

Granulosa C
ells

Aromatase
Estrone
Estradiol

Estriol
 Ovarian Hormones
 Hormonal cycle
2 peaks of estrogens
before ovulation
midluteal phase
estradiol secretion rate:
early follicular phase 36 μg/day
before ovulation 380 μg/day
midluteal phase 250 μg/day
in men 50 μg/day
 Ovarian Hormones
 Hormonal cycle
1 peak of progesteron: midluteal phase
plasma progesterone level:
follicular phase 0.9 ng/mL(3 nmol/mL)
midluteal phase 18 ng/mL(60 nmol/mL)
in men 0.3 ng/mL(1 nmol/mL)
 Ovarian Hormones

 Hormonal cycle
 Two days before
ovulation, LH
increases 6-10 folds.
FSH secretion
increases 2-3 folds at
the same time
 LH surge: caused by
positive feedback
induced by peak
estrogen secretion
 LH & FSH act jointly
to cause rapid
distending of the
follicle
 Ovarian Hormones
 Ovarian androgens
T, A2 , DHEA
potency ratio: T: A2:DHEA=20:2:1
origin:theca cells-A2,stroma cells-T
functions:
growth of axillary and pubic hair
promoting protein synthesis
elevating before ovulation: promoting follicular atresia
and libido(sexual lust)
 Ovarian Hormones
 Ovarian inhibins and activins:
polypeptide hormones
granulosa cell origin
inhibin: FSH↓
activin: FSH↑
local moderator(autocrine/paracrine)
 Feedback Effect

 Negative Feedback
At level of hypothalamus/pituitary:
 Circular estrogens inhibit LH & FS
H secretion
 Circular progesterone (low) potentia
tes estrogen feedback effects
 Circular inhibin inhibits FSH secreti
on
At level of ovary:
 Receptors for LH (thecal cells) and
FSH (granulosa cells) increase in ma
turing follicle
 Cellular hypertrophy
 Proliferation of granulosa/theca incr
eases circulating estrogens that parti
cipate in negative feedback
 Feedback Effect

 Positive Feedback
At level of hypothalamus/pituitary:
 Increase in circulating estrogen and prog
esterone
 Positive feedback by estrogen on pituitar
y FSH & LH secretion  FSH/LH peak
 LH peak induces ovulation
At level of ovary
 Theca: increased androgen
 Granulosa: LH/FSH receptors induced;
aromatase induced; increased estrogen
 Proliferating cells elevate estrogen to crit
ical concentrations(Circular estradiol lev
el >200 pg/ml sustained for 2 days is req
uired for positive feedback)
 Summary

 Every 28 days, FSH and LH from pituitar

y cause new ovarian follicles to grow. Dur
ing early growth of the follicles, inhibinB
is low and FSH is modestly elevated, foste
ring follicular growth. estrogen is elevated
, holding LH secretion in check and causin
g the proliferative changes of uterine endo
metrium.

 At 36~48 hours before ovulation,the estro

gen feedback becomes positive,causing L
H peak. Ovulation happens 9 hours after L
H peak at the 14th day of cycle.FSH also
peaks induced by a small preovulatory rise
of progesterone,despite a small rise in inhi
binB.
 Summary

 After ovulation, corpus luteum secretes larg

e quantities of estrogen and progesterone, c
ausing the secretory changes in uterine endo
metrium. Meanwhile LH/FSH secretion is i
nhibited with the help of the inhibinB rise.

 In another two weeks, corpus luteum degen

erates, causing a decrease in progesterone a
nd estrogen. The sudden reduction of ovaria
n hormones causes shedding of uterine endo
metrium, thus menstruation occurs. The inhi
bition to LH/FSH is removed,a new crop of
follicles is recuited.

 Then a new cycle follows.

 Influence from Other Endocrine Glands
 Thyroid: thyroxine/T4 and triiodothyroxine/T3
 sustain normal menstruation and reproduction
 hypothyroidism
before puberty: delayed puberty
during puberty: hypomenorrhea,oligomenorrhea and even amenorrhea
infertility
spontaneous abortion and fetal malformation
 hyperthyroidism
mild: menorrhagia,polymenorrhea and even disfunctional uterine bleeding
severe: hypomenorrhea,oligomenorrhea and even amenorrhea
infertility
 Influence from Other Endocrine Glands
 Adrenal: androgen
 small amount of androgen is necessary for development of axillary and
pubic hair, muscles and physique.
 excessive androgens will inhibit GnRH secretion and antagonize estrog
ens.
 congenital adrenal hyperplasia,CAH:
21-hydroxylase deficiency→cortical hormones shortage → adrenocort
icotropic hormone/ACTH compensationally increase→ adrenal androgens
increase→female pseudohermaphroditism or masculinization
 Influence from Other Endocrine Glands
 Pancreas: insulin
 sustain ovarian function
 IDDM: ovarian hypofunction
 hyperinsulinemia in insulin-resistance: insulin↑→ovarian androgen↑→
hyperandrogenemia →dysmenorrhea and amenorrhea
Functions of Ovarian Hormones
 Functions of Ovarian Hormones

 2 classes of ovarian sexual hormones:

 Estrogens(18-C)
most important and potential: estradiol
 Progestins(21-C)
most important: progesterone
 Functions of Ovarian Hormones
Estrogens Progestins
Myometrium Cell proliferation and hypertrophy↑ Excitability↓
blood supply↑ contraction↓
oxytocin sensitivity↑ Oxytocin sensitivity↓
Endometrium Glands and stroma proliferation and Transition from proliferative phase to
restoration↑ secretory phase
Cervix Cervical os relaxed and expanded Cervical os closed
Mucus secretion and elasity↑ Mucus secretion and elasity↓
Oviducts Amplitude of rhythmic contraction↑ Amplitude of rhythmic contraction↓

Vagina Epithelial cell proliferation and Epithelial cells sloughing↑

cornification↑
Intracellular glycogens↑
Ovary Oocyte maturation↑
Granulosa cell proliferation and Granulosa cell proliferation↓
differentiation↑
Hypothalamus Negative/positive feedback to Enhance the feedback effect of estrogens
Pituitary regulate synthesis and secretion of
gonadotropins
 Functions of Ovarian Hormones

Estrogens
breast Development of mammary ducts
Pigmentation of areolas
metabolism Water and sodium retention↑
Protein synthesis↑
Fat deposition of female style
other Osteoplastic activity↑
HDL↑ LDL/Cholesterol↓
Progestins
Development of mammary lobules and alveoli
Water and sodium evacuation↑
Basal body temperature raised by 0.3~0.5℃
after ovulation
 Functions of Ovarian Hormones
 Antagonizing effects
endometrium
uterine contraction and exitability
sensitivity to oxytocin
oviduct movement
cervical mucus
vaginal epithelial proliferation
water-sodium metabolism

 Cooperative effects
genitalia development
breast development
 Functions of Ovarian Hormones
 Unique effects
 Estrogen
promote osteoplastic activity
improve blood-fat composition and prevent atherosclerosis

 Progesterone
excite temperature regulating centrum in hypothalamus→BBT
increase after ovulation →minitoring ovulation
 Several questions to think about

 How can we infer that ovulation occurs?

 What hormones are produced by what cells of

the ovaries?

 In which aspects estrogen and progesterone co

operate?In which aspects they counteract?
THANKS FOR ATTENTION