final female physiology handout for med studes part i
TRANSCRIPT
8/3/2019 Final Female Physiology Handout for Med Studes Part i
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Female Physiology
8/3/2019 Final Female Physiology Handout for Med Studes Part i
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Female Physiology
Outline of the Lecture
I. AnatomyII. Female Hormonal System
III. Physiology of MenstruationIV. Hormones of Pregnancy and
Lactation
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Female Physiology
External Female Genitalia
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Female Physiology
Internal Female Genitalia
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Female Physiology
Uterus
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Female Physiology
Fallopian Tube
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The Ovary
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The Ovarian Follicle
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Mature Graffian Follicle
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OVARIAN DEVELOPMENT:
CHRONOLOGY
6 weeks
12-24 weeks
Birth
Puberty
Reproduction span
13 – 46 y/o
Primordial germ cells
Oogonia proliferation
migrate
Genital ridge
400 oocytes
400,000 oocytes
2,000,000 oocytes
Primary oocytes in
meiotic arrest
7,000,000
ATR
ESIA
Mitotic Division
1st Meiotic Division
arrested at diplotene stage(Prophase)
Resumption of the1st Meiotic Division
46 xx
46 xx
46 xx
23 x
23x
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Secondary oocyte, 23x
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Female Physiology
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Female Physiology
NORMAL GAMETOGENESIS
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Female Physiology
The Ovary
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Female Physiology
Hypothalamus and pituitary gland
www.driesen.com/pituitarygland.jpg
Secretory cells; release anterior pituitary hormones
Neurosecretory cells in hypothalamus
For posterior pituitary gland For anterior pituitary gland
Mammilary
body
Capillary bed around
terminals of neurosecretorycells; hypothalamic
hormones released here
Artery
Posterior pituitary gland
Terminals release posterior
pituitary hormones
Artery
Anterior pituitary gland
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Female Physiology
Female Hormonal System
Hypothalamus
GnRH
Anterior Pituitary Gland
FSH
LH
OvariesEstrogen
Progesterone
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Female Physiology
GnRH Produced in the arcuate nucleus in themedial basal hypothalamus and
transported to the anterior pituitary via the
HHPS
Released in pulsatile manner every 1-2
hours
Stimulates the synthesis and release of FSH and LH from the anterior pituitary
gland
Female Hormonal System
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Female Physiology
GnRH Route of secretion:
Hypothalamus, Anterior hypothalamus
Medial basal / tuberal hypothalamus, (ArcuateNucleus)
Hypothalamic – Hypophysial Tract
Anterior lobe of the pituitary
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Female Physiology
Basophilic cells of the anterior pituitary gland
Small glycoprotein with a molecular
weight of 30,000Same α subunits for FSH, LH, TSH
and hCG
Female Hormonal System
G
O
N
A
D
O
T
R
O
P
IN
S
F
S
H
L
H
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Female Physiology
FSH LH
α α β β
Gonadotropins: FSH and LH
Hall JE. Neuroendocrine control of reproduction. Symposium on Frontiers inReproductive Endocrinology, Washington, 1997
Basophilic cells
Structural similarity
Identical α subunits
Different β subunitsSecretion
Common cell type:
basophilic cells
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Female Physiology
Acts on the granulosa cellsstimulate follicular growth
Production of estrogen,
FSH and LH receptors
Female Hormonal System FSH
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Female Physiology
Acts synergistically with FSHfor follicular maturation
Ovulation
Acts on the theca cells for
production of androgens
Acts on the granulosa cell for
production of progesterone
Female Hormonal System LH
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Female Physiology
Female Hormonal System
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Female Physiology
Average duration:28 ± 7 days
< 21 dayspolymenorrhea
> 35 days
oligomenorrhea
The Menstrual Cycle
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Female Physiology
Ovarian Cycle
Endometrial Cycle
The Menstrual Cycle
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
Ovulation
P4
LH
E2
FSH
Follicular phase
Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUAL
CYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
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Female Physiology
The Monthly Ovarian Cycle
Depends completely
on the gonadotropic
hormones FSH & LH
Ages 9 – 12:
↑ FSH and LH
Ages 11 - 15:1st menstruation
(menarche)
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Female Physiology
The Ovarian Cycle
2 Phases
Follicular
LutealFollicular phase
Lutealphase
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Female Physiology
Follicular Phase of theOvarian Cycle
At birth:ovum + single layer of
granulosa cell
PRIMORDIAL FOLLICLE (2M)
nourishment for the ovum
oocyte maturation inhibiting
factor
Primordial follicle
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Female Physiology
Follicular Phase of theOvarian Cycle
At puberty:↑ FSH > LH
meiosis proceeds
enlargement of the ovum
additional layer of granulosa
cells
PRIMARY FOLLICLE (400,000)
Primordial follicle
Primary follicle
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Female Physiology
Follicular Phase of theOvarian Cycle
rapid proliferation of
granulosa cells
formation of theca cells
Primordial follicle
Primary follicle
Pre-antral follicle
PRE-ANTRAL FOLLICLE
N G D
O T E
N P
E
N
D
E
N
T
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Female Physiology
Follicular Phase of theOvarian Cycle
↑ FSH
accelerated growth of
6-12 primary follicles
rapid proliferation of
granulosa cells
formation of theca cells
Primordial follicle
Primary follicle
Preantral follicle
N G D
O T E
N P
E
N
D
E
N
T
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Female Physiology
Follicular Phase of theOvarian Cycle
the rapidly proliferating
granulosa cells secrete
follicular fluid ( very rich in estrogen )
Primordial follicle
Primary follicle
Preantral follicle
ANTRAL FOLLICLE
antral follicle
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Female Physiology
Follicular Phase of theOvarian Cycle
FSH
Primordial follicle
Primary follicle
Preantral follicle
antral follicle
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Female Physiology
Follicular Phase of theOvarian Cycle
VESICULAR FOLLICLEaccelerated growth in the
antral follicle due to FSH
estrogen granulosa cells
FSH + estrogen LH receptors
LH + estrogen growth of theca cells
Primordial follicle
Primary follicle
Preantral follicle
Antral follicle
(+)
↑↑ FSH receptors
(+)
(+)vesicular follicle
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Female Physiology
Follicular Phase of theOvarian Cycle
FULL MATURATION OF ONLY1 FOLLICLE, ATRESIA OF
THE REMAINDER
Intrinsic positive feedback onthe one dominant follicle
↑↑↑ estrogen hypothalamus
atresia of the
other follicles
Primordial follicle
Primary follicle
Preantral follicle
Antral follicle
(-)
↓ FSH
vesicular follicle
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Female Physiology
Ovulation
FOLLICULARPHASE
LUTEALPHASE
O
V
U
LA
TI
O
N
Follicular phase
Lutealphase
Ovulation
LH
P4
E2
FSH
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Female Physiology
Ovulation
- occurs 14 days before the onset of
menstruation
St f l ti b i i ith d t i di l
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Female Physiology 39
Steps of ovulation, beginning with dormant primordial
follicle that grows and matures and is eventually released
from the ovary into the fallopian tube
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Female Physiology
Stages of ovulationMotta P. Dept Of Anatomy, University "La Sapienza", Rome. Science Photo Library
False-color scanning electronmicrography of the ovary
C
Germinalepithelium
Surface of ovary atovulation
Ovulationprocess
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Female Physiology
Need for LH in Ovulation
Necessary for final follicular growth and ovulation
Primordial follicle
Primary follicle
Preantral follicle
Antral follicle
vesicular follicle
LH
Ovulation
FSH
E2
P4
Follicular phase
Lutealphase
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Female Physiology
Need for LH in Ovulation
LH SURGECause:
sudden estrogen peak
beginning progesterone
secretion
2 days before ovulation: ↑LH
peak: 10-12 hours before
ovulation
Primordial follicle
Primary follicle
Preantral follicle
Antral follicle
vesicular follicle
LH
Ovulation
FSH
E2
P4
Follicular phase
Lutealphase
O l i
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Female Physiology
Temporal relationship
between estradiol and LHsurges and ovulation
Ovulation34-36
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
Ovulation
P4
LH
E2
FSH
Follicular phase
Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUAL
CYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
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Female Physiology
Luteal Phase of the Ovarian Cycle
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Female Physiology
granulosa cell:progesterone > estrogen
theca cell: androgensandrostenedione
testosterone
Luteal Phase of the Ovarian Cycle
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Female Physiology
granulosa cells
theca cells
progesterone > estrogen
Luteinizing Functions of LH
LH
ovulation LUTEIN CELLS
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
Ovulation
P4
LH
E2
FSH
Follicular phase
Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUAL
CYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
Involution of the Corpus Luteum &
8/3/2019 Final Female Physiology Handout for Med Studes Part i
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Female Physiology
estrogen
progesterone
↓ FSH and LH
Inhibin FSH
Involution of the Corpus Luteum &
Onset of the Next Ovarian Cycle
(-) Anterior Pituitary
(-)
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
Ovulation
P4
LH
E2
FSH
Follicular phase
Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUAL
CYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
Involution of the Corpus Luteum &
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Female Physiology
↓ FSH & LH
corpus albicans
Involution of the Corpus Luteum &
Onset of the Next Ovarian Cycle
corpus luteum
regresses
(12th day after ovulation)
h C
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Female Physiology
corpus luteum7-8 days
1.5 cm
t corpus albicans12th day
( day 26 of menses)
The Corpus Luteum A B
EndoscopeimagesDevelopment of
follicle (A);
Graafian follicle(B); rupture scar
after ovulation(C,D); corpus
luteum after
ovulation (E)
D E
A B C
D E
Involution of the Corpus Luteum &
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Female Physiology
Involution of
the corpus luteum
MENSTRUATION
Involution of the Corpus Luteum &
Onset of the Next Ovarian Cycle
↓ estrogen and
progesterone
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
Ovulation
P4
LH
E2
FSH
Follicular phase
Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUAL
CYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
H l h i th f l
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Female Physiology 55
Hormonal changes in the female
reproductive system
Ovarian cycle
Uterine cycle
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
Ovulation
P4
LH
E2
FSH
Follicular phase
Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUALCYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
The Monthl Endometrial C cle and
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Female Physiology
2 Phases
proliferative
secretory
The Monthly Endometrial Cycle andMenstruation
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Female Physiology
begins on day 1 of menstruation
stroma and epithelial cells
proliferate rapidly
progressive growth of
endometrial glands which
secrete thin mucus into the
cervical canal
Proliferative Phase (Estrogen Phase)
Proliferativephase
Secretoryphase
Follicular phase
Lutealphase
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Female Physiology
occurs after ovulation
estrogen: additional
cellular proliferation in
the endometrium
progesterone: marked
swelling and secretory
development of the
endometrium
Secretory Phase (Progesterone Phase)
Proliferativephase
Secretoryphase
Follicular phase
Lutealphase
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Female Physiology
↑↑ in blood supply
PURPOSE:
to prepare the
endometrium for possible
implantation of a
fertilized ovum
Secretory Phase (Progesterone Phase)
Proliferativephase
Secretoryphase
Follicular phase
Lutealphase
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Female Physiology
2 days before menses(day26):
CL regresses: ↓ E / P
no support to endometrium
vasospasm of blood vessels
due to prostaglandins
Menstruation
Proliferativephase
Secretoryphase
Follicular phase
Lutealphase
Ovulation
LH
E2
P4
FSH
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Female Physiology
endometrial necrosis
slough off from the uterus
hemorrhage
MENSES
Menstruation
Proliferativephase
Secretoryphase
Follicular phase
Lutealphase
Ovulation
LH
E2
P4
FSH
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Female Physiology
40 ml of blood lossnon-clotting due to
fibrinolysin
ceases after 4-7 days due
to re-epithelialization
The Menstrual Blood
O l ti
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
Ovulation
P4
LH
E2
FSH
Follicular phase
Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUAL
CYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
Th O i S id
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Female Physiology
Estrogen
Progestins
The Ovarian Steroids
Th E
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Female Physiology
Sources:
ovaries
placenta
adrenal cortex
The Estrogens
3 T f E t
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Female Physiology
ß- estradiol major estrogen produced by
the ovaries
Estronemajority comes from the
peripheral conversion of
androgens; some from the ovaries
Estriol oxidative product of estradiol
and estrone
3 Types of Estrogens
P t
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Female Physiology
The most important progestin
Sources:
ovaries ( 2nd half )
placenta
adrenal cortex
Progesterone
Biosynthesis of Estrogen and Progesterone
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Female Physiology
AcetateCholesterol
Pregnenolone
Progesterone
17-Hydroxyprogesterone
Androstenedione
Estrone
P450scc
P450c1717αOHlase
3β-OHSDΔ5,4 isomerase
17-Hydroxypregnenolone
Dehydroepidandrosterone
P450c17, 20 lyase P450c1717αOHlase
P450c17
17, 20 lyase
17β-OHSD
17βHSD
Δ5 pathwayDHEA
pathway
Δ4 pathwayProgesterone
pathway
P450arom
Testosterone
Estradiol
P450arom
Biosynthesis of Estrogen and Progesterone
3β-OHSD
Δ5,4
isomerase
Graafian follicle showing arrangement of
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Female Physiology
Graafian follicle showing arrangement of
follicle cells around the Oocyte
Hormone production inthe graafian follicle
Theca cells Androstenedione
Testosterone
Granulosacells
Estrone
Estradiol
Corpusluteum
ProgesteroneEstrogen
Follicular Phase of the
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Female Physiology
Follicular Phase of theOvarian Cycle
VESICULAR FOLLICLE
accelerated growth in the
antral follicle
estrogen granulosa cells
FSH + estrogen LH receptors
LH + estrogen growth of theca cells
Primordial follicle
Primary follicle
Preantral follicle
Antral follicle
(+)↑↑ FSH receptors
(+)
(+)vesicular follicle
OVARIAN STEROIDOGENESIS
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Female Physiology
OVARIAN STEROIDOGENESIS
Speroff L, et al. Clinical
Gynecologic Endocrinology
and Infertilty, ed 6, Lippincott
Williams & Wilkins, Baltimore,
1999
LH
Andros-tenedione
Theca cell
FS
H Aromatization
Estrone
Granulosa
cell
Two-cell two-gonadotropin
hypothesis
Compartmentalization of
steroid hormone
synthesis in the
developing follicle
Cholesterol
Estradiol
Testosterone
Testosterone
Andro-
stenedione
Andro-
stenedione
Estrone
cp450
Ovulation
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
Ovulation
P4
LH
E2
FSH
Follicular phase Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUAL
CYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
Biosynthesis of Estrogen and Progesterone
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Female Physiology
AcetateCholesterol
Pregnenolone
Progesterone
17-Hydroxyprogesterone
Androstenedione
Estrone
P450scc
P450c1717αOHlase
3β-OHSDΔ5,4 isomerase
17-Hydroxypregnenolone
Dehydroepidandrosterone
P450c17, 20 lyase P450c1717αOHlase
P450c1717, 20 lyase
17β-OHSD
17βHSD
Δ5 pathwayDHEA
pathway
Δ4 pathwayProgesterone
pathway
P450arom
Testosterone
Estradiol
P450arom
Biosynthesis of Estrogen and Progesterone
3β-OHSD
Δ5,4
isomerase
Fate of Estrogen and Progesterone
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Female Physiology
Estrogen liver
urine
Progesterone liver
urine
Fate of Estrogen and Progesterone
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Development and
maturation of the
female reproductive
organs – uterus
tubes
ovaries
external genitalia
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Development and
maturation of the
secondary female sexual
characteristics
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Promotes proliferative
changes in the uterine
endometrium
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Extra fat deposition into
the subcutaneous tissue
of the breasts, buttocks
and thighs
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Increase skin
pigmentation of the
nipples, areola and
pubic region
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Stromal / ductal growth
of the breasts
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Maintenance of the
normal structure of the
skin and blood vessel
Accelerates growth and
closure of the epiphyses
of long bones
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Growth of the ovarian
Follicles
Production of cervical
mucus that is clear,
watery, and slightly
alkaline
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Osteoblastic activity
↓ osteoclastic activity
At menopause:
* ↑ osteoclastic activity
* ↓ bone matrix
* ↓ deposition of bone
calcium and P04-
Female Hormonal System
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Female Physiology
Female Hormonal System
Estrogen
Increased protein
synthesis in the liver
Enhances blood
coagulation
sodium and water
retention
Female Hormonal System
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Female Physiology
Female Hormonal System
Progesterone
Glandular and
secretory development
in reproductive organs
Lobuloalveolar growth
of the breasts
Female Hormonal System
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Female Physiology
Female Hormonal System
Progesterone
Promotes secretory
changes in the uterine
endometrium
↓ frequency and
intensity of the uterine
contractions
Female Hormonal System
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Female Physiology
Female Hormonal System
Progesterone
Promotes secretory
changes in the mucuosal
lining of the fallopian
tube necessary for the
nutrition of the fertilized
ovum as it travels the
tube
Female Hormonal System
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Female Physiology
Female Hormonal System
Progesterone
Production of cervical
mucus that is scanty,
viscous and acidic
Increases the basal body
temperature
Ovulation
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Female Physiology
Endo-crinecycle
Ovarianhisto-
logy
Endo-metrial
histo-
logy
Menses 14 28
P4
LH
E2
FSH
Follicular phase
Lutealphase
Proliferativephase
Secretoryphase
Palter SF, Olive DL.In Berek JS, et al.
Novaks Gynecology,
ed 12, Williams andWilkins, 1996
MENSTRUAL
CYCLE
Relative pattern
of ovarian,
uterine, and
hormonal
variation along
the normal
cycle
Control of the Female Hormonal System
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Control of the Female Hormonal System
HYPOTHALAMUS
GnRH
ANTERIOR PITUITARY
FSH LH
OVARIES
ESTROGEN PROGESTERONE
(+)
(+)
(+)
(-)
(-)
(-)
(-) (-)