Download Control of Menstrual Cycle

Physiology
of Reproduction
in Women
Cheng Biheng 程苾恒
M.D.
Dept. of Obstetrics&Gynecology
Renmin Hosp. of Wuhan Univ.
Anatomy of Female Reproductive System
Physical Development
in A Woman’s life
Physical Development in A Woman’s life
 6 stages: a process in progress

Neonatal period：4w
influence from maternal estrogens→
plump vulva
breasts swelling
milk secretion
false menses
Physical Development in A Woman’s life
 Childhood: 4w～12y
inhibited HPOA: ovarian follicle growth stops at preantral
stage
puerile genitalia
vagina: long and narrow,thin epithelium,low acidity
uterus: body:cervix=1:2
rapid physical outgrowth/slow genitalia development
Physical Development in A Woman’s life

Puberty：
menarche
puerile genitalia→adult genitalia
Physical Development in A Woman’s life



Sexual maturity：18y, 30 years
regular cyclic ovulation and menstruation
Menopausal transition period:45y～55y/52y
menses irregular/cease
Postmenopausal period:
senility >60y
Physical Development in A Woman’s life
☆perimenopausal period(WHO,1994)
(the platitude"climacteric period"was abolished)
Ovaries unresponsive to gonadotropins, function declines, sexual
cycle disappear caused by reduced primordial follicles;
No secretion of progesterone and estradiol by ovaries,
aromatization of androstenedione in the circulation only;
Atrophy of the uterus and vagina;
Typical symptom: hot flashes due to unsteady vasomotorial
function, possibly with night sweating.
Physical Development in A Woman’s life
 Characteristics of puberty


age of puberty: ↓1~3 months/decade,10~19y(WHO)
physical burst: conformation and function
Physical Development in A Woman’s life

first sexual characteristics
mons pubis: swelling
labium majus/minus: plump and pigmentation
vagina: longer and wider, thicker epithelium
uterus: body:cervix=2:1
Physical Development in A Woman’s life
 second sexual characteristics
high-pitched tone
swelling breasts
axillary and pubic hair
female-specific pelvis
and fat deposition
Physical Development in A Woman’s life
 4 stages of puberty




Thelarche: breasts
Adrenarche: hair
Growth spurt
Menarche: the first menses
Physiology of Menstruation
Physiology of Menstruation
 Definition
 Age: mostly 13~14y
>17y: abnormal
 Traits: color/coagulablity/origin/content
 Interval: 21~35d
 Duration: 2~7d
 Amount:30~50mL
☆menorrhagia: >80mL
How
Menstruation Forms?
Ovarian Cycle
 Functions of ovaries


Reproduction: oocyte
Endocrine: hormone
Ovarian Cycle
7,000,000
400-500 ovulations
in a life
2,000,000
300,000
20 weeks
of gestation
Birth
Puberty
Ovarian Cycle
 Development of ovarian follicles


follicular phase
luteal phase
Ovarian Cycle
 Follicular phase
primordial follicle
 preantral follicle
 antral follicle
 preovulatory follicle/Graafian follicle
 atretic follicle

Ovarian Cycle
Ovarian Cycle
 Structure of a preovulatory follicle
Ovarian Cycle
 Ovulation
Ovarian Cycle
 Ovulation
Ovarian Cycle
 Luteal phase



corpus hemorrhagicum
corpus luteum
corpus albicans
Ovarian Cycle
Uterine Cycle
 2 layers and 2 kinds of arteries


stratum functionale——spiral artery(long、coiled)
stratum basale——basilar artery(short、straight)
Uterine Cycle
Uterine Cycle
Cycle of Other Sites in Female Genitalia
 Cervical cycle
estrogen: thin/alkaline
progesterone:thick/tenacious/cellular
Cycle of Other Sites in Female Genitalia
 Vaginal cycle
estrogen: epi-cornified/glycogens&acidity↑
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
menstruation caused by hyperemia and edema of interstitial
tissue 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)
also 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 aromatase
and estrogen↑;inducing LH-R; synthesis of IGF/IGF-R、inhibinA and
activins.
follicle recruitment
LH
theca cells: androgen↑
granulosa cells: luteinized and progesterone↑
preovulatory mature of oocyte(completing first meiosis)
facilitaing ovulation
sustain luteal function
human chorionic gonadotropin(HCG)
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 lipoprotein)
 cholesterol→pregnenolone(catalyzed by
desmolase,LH via cyclic AMP)
 pregnenolone →androstenedione in 2 routes
androstenedione →estrone(catalyzed by aromatase,FSH
via cyclic AMP)
 testosterone →estradiol(catalyzed by
aromatase,FSH via cyclic AMP)
Ovarian Hormones
 Synthesis of estrogen
2 cell-2 gonadotropin hypothesis(Falck,1959)
 estrogens are synthesized by theca cells and granulosa cells under the
cooperative 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
into E1 and E2
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 &
FSH secretion
Circular progesterone (low)
potentiates estrogen feedback effects
Circular inhibin inhibits FSH
secretion
At level of ovary:
Receptors for LH (thecal cells) and
FSH (granulosa cells) increase in
maturing follicle
Cellular hypertrophy
Proliferation of granulosa/theca
increases circulating estrogens that
participate in negative feedback
Feedback Effect
 Positive Feedback






At level of hypothalamus/pituitary:
Increase in circulating estrogen and
progesterone
Positive feedback by estrogen on
pituitary 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
critical concentrations(Circular estradiol
level >200 pg/ml sustained for 2 days is
required for positive feedback)
Summary
 Every 28 days, FSH and LH
cause new ovarian follicles to
grow. estrogen is elevated,
causing the proliferative
changes of uterine
endometrium.
 before ovulation,the estrogen
feedback becomes positive,
causing LH peak. Ovulation
happens 9 hours after LH
peak. FSH also peaks.
Summary
 After ovulation, corpus luteum
secretes large quantities of estrogen
and progesterone, causing the
secretory changes in uterine
endometrium.
 In another two weeks, corpus luteum
degenerates, causing a decrease in
progesterone and estrogen, resulting
in shedding of uterine endometrium.
 The inhibition to LH/FSH is
removed,a new crop of follicles is
recuited.
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
estrogens.

congenital adrenal hyperplasia,CAH
Influence from Other Endocrine Glands
 Pancreas: insulin



sustain ovarian function
IDDM: ovarian hypofunction
hyperinsulinemia in insulin-resistance
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
Myometrium
Endometrium
Cervix
Oviducts
Vagina
Ovary
Hypothalamus
Pituitary
Estrogens
Cell proliferation and hypertrophy↑
blood supply↑
oxytocin sensitivity↑
Glands and stroma proliferation and
restoration↑
Cervical os relaxed and expanded
Mucus secretion and elasity↑
Amplitude of rhythmic contraction↑
Epithelial cell proliferation
cornification↑
Intracellular glycogens↑
Oocyte maturation↑
Granulosa cell proliferation
differentiation↑
Progestins
Excitability↓
contraction↓
Oxytocin sensitivity↓
Transition from proliferative phase
secretory phase
Cervical os closed
Mucus secretion and elasity↓
Amplitude of rhythmic contraction↓
and
Epithelial cells sloughing↑
and
Granulosa cell proliferation↓
to
feedback
Negative/positive
regulate synthesis and secretion of
gonadotropins
Enhance the feedback effect of estrogens
to
Functions of Ovarian Hormones
breast
metabolism
other
Estrogens
Development of mammary ducts
Pigmentation of areolas
Water and sodium retention↑
Protein synthesis↑
Fat deposition of female style
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
cooperate?In which aspects they counteract?
THANKS FOR ATTENTION