Female Physiology

Outline of the Lecture

I. Anatomy II. Female Hormonal System III.Physiology of Menstruation IV.Hormones of Pregnancy and Lactation

Female Physiology

External Female Genitalia

Female Physiology

Internal Female Genitalia

Female Physiology

Uterus

Female Physiology

Fallopian Tube

Female Physiology

The Ovary

Female Physiology

The Ovarian Follicle

Female Physiology

Mature Graffian Follicle

Female Physiology

OVARIAN DEVELOPMENT: CHRONOLOGY

6 weeks
46 xx

Primordial germ cells migrate Genital ridge

46 xx

12-24 weeks

Mitotic Division

Oogonia proliferation Primary oocytes in meiotic arrest 2,000,000 oocytes A T R E S I A

7,000,000

1st Meiotic Division arrested at diplotene stage (Prophase)

46 xx

Birth Puberty
Resumption of the 1st Meiotic Division

23 x

400,000 oocytes 400 oocytes

23x

Reproduction span 13 46 y/o

Female Physiology

Female Physiology

Secondary oocyte, 23x

Female Physiology

NORMAL GAMETOGENESIS

Female Physiology

The Ovary

Female Physiology

Hypothalamus and pituitary gland

Neurosecretory cells in hypothalamus For posterior pituitary gland For anterior pituitary gland

Mammilary body

Artery Anterior pituitary gland

Capillary bed around terminals of neurosecretory cells; hypothalamic hormones released here Artery Posterior pituitary gland

Terminals release posterior pituitary hormones Secretory cells; release anterior pituitary hormones

www.driesen.com/pituitarygland.jpg Female Physiology

Female Hormonal System

Hypothalamus
GnRH

Anterior Pituitary Gland

FSH LH

Ovaries
Estrogen Progesterone
Female Physiology

Female Hormonal System

GnRH
Produced in the arcuate nucleus in the medial 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 Physiology

GnRH Route of secretion:

Hypothalamus, Anterior hypothalamus Medial basal / tuberal hypothalamus, (Arcuate Nucleus)

Hypothalamic Hypophysial Tract

Anterior lobe of the pituitary

Female Physiology

Female Hormonal System

G O N A D O T R O P I N S

F S Small glycoprotein with a molecular H weight of 30,000 L H

Same subunits for FSH, LH, TSH and hCG

Basophilic cells of the anterior pituitary gland

Female Physiology

Gonadotropins: FSH and LH

Structural similarity
FSH LH

Identical subunits Different subunits

Secretion
Basophilic cells

Common cell type: basophilic cells

Hall JE. Neuroendocrine control of reproduction. Symposium on Frontiers in Reproductive Endocrinology, Washington, 1997 Female Physiology

Female Hormonal System FSH

Acts on the granulosa cells stimulate follicular growth Production of estrogen, FSH and LH receptors

Female Physiology

Female Hormonal System LH

Acts synergistically with FSH for follicular maturation Ovulation Acts on the theca cells for production of androgens Acts on the granulosa cell for production of progesterone
Female Physiology

Female Hormonal System

Female Physiology

The Menstrual Cycle

Average duration: 28 7 days < 21 days polymenorrhea > 35 days oligomenorrhea

Female Physiology

The Menstrual Cycle

Ovarian Cycle

Endometrial Cycle

Female Physiology

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Endometrial histology Menses 14 28 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

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)
Female Physiology

The Ovarian Cycle

2 Phases

Follicular Luteal

Follicular phase

Luteal phase

Female Physiology

Follicular Phase of the Ovarian Cycle

Primordial follicle

At birth: ovum + single layer of granulosa cell

PRIMORDIAL FOLLICLE (2M)

nourishment for the ovum

oocyte maturation inhibiting factor
Female Physiology

Follicular Phase of the Ovarian Cycle

Primordial follicle Primary follicle

At puberty: FSH > LH meiosis proceeds enlargement of the ovum additional layer of granulosa cells

PRIMARY FOLLICLE (400,000)

Female Physiology

Follicular Phase of the Ovarian Cycle

N G D O T E N P E N D E N T

Primordial follicle Primary follicle

Pre-antral follicle

rapid proliferation of granulosa cells formation of theca cells

PRE-ANTRAL FOLLICLE

Female Physiology

Follicular Phase of the Ovarian Cycle

N G D O T E N P E N D E N T

Primordial follicle Primary follicle

FSH accelerated growth of 6-12 primary follicles rapid proliferation of granulosa cells formation of theca cells

Preantral follicle

Female Physiology

Follicular Phase of the Ovarian Cycle

Primordial follicle Primary follicle

Preantral follicle

the rapidly proliferating granulosa cells secrete follicular fluid ( very rich in estrogen )

antral follicle

ANTRAL FOLLICLE

Female Physiology

Follicular Phase of the Ovarian Cycle

Primordial follicle Primary follicle

Preantral follicle

FSH

antral follicle

Female Physiology

Follicular Phase of the Ovarian Cycle

Primordial follicle Primary follicle

VESICULAR FOLLICLE accelerated growth in the antral follicle due to FSH estrogen
(+)

Preantral follicle

granulosa cells
FSH receptors

Antral follicle

FSH + estrogen
vesicular follicle

(+)

LH receptors

LH + estrogen

(+)
growth of theca cells

Female Physiology

Follicular Phase of the Ovarian Cycle

Primordial follicle Primary follicle

FULL MATURATION OF ONLY 1 FOLLICLE, ATRESIA OF THE REMAINDER Intrinsic positive feedback on the one dominant follicle estrogen
(-)
hypothalamus

Preantral follicle

Antral follicle

vesicular follicle

atresia of the other follicles

FSH

Female Physiology

Ovulation
Ovulation LH O V U FSH L A T I O N P4

E2

FOLLICULAR PHASE Follicular phase

LUTEAL Luteal PHASE phase

Female Physiology

Ovulation
- occurs 14 days before the onset of menstruation

Female Physiology

Steps of ovulation, beginning with dormant primordial follicle that grows and matures and is eventually released from the ovary into the fallopian tube

Female Physiology

39

Stages of ovulation
Motta P. Dept Of Anatomy, University "La Sapienza", Rome. Science Photo Library

False-color scanning electron micrography of the ovary

Germinal epithelium
Female Physiology

Surface of ovary at ovulation

Ovulation process

Need for LH in Ovulation

Primordial follicle Ovulation Primary follicle LH P4 E2 Preantral follicle FSH

Necessary for final follicular growth and ovulation

Follicular phase

Luteal phase Antral follicle

vesicular follicle

Female Physiology

Need for LH in Ovulation

Primordial follicle Ovulation Primary follicle LH P4 E2 Preantral follicle FSH

Follicular phase

Luteal phase Antral follicle

LH SURGE Cause: sudden estrogen peak beginning progesterone secretion 2 days before ovulation: LH peak: 10-12 hours before ovulation

vesicular follicle

Female Physiology

Ovulation
34-36

Temporal relationship between estradiol and LH surges and ovulation

Female Physiology

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Endometrial histology Menses 14 28 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

Female Physiology

Luteal Phase of the Ovarian Cycle

Female Physiology

Luteal Phase of the Ovarian Cycle

granulosa cell: progesterone > estrogen theca cell: androgens androstenedione testosterone

Female Physiology

Luteinizing Functions of LH
granulosa cells theca cells
LH ovulation

LUTEIN CELLS

progesterone > estrogen

Female Physiology

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Endometrial histology Menses 14 28 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

Female Physiology

Involution of the Corpus Luteum & Onset of the Next Ovarian Cycle

estrogen progesterone

(-)

Anterior Pituitary

FSH and LH

Inhibin
Female Physiology

(-)

FSH

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Endometrial histology Menses 14 28 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

Female Physiology

Involution of the Corpus Luteum & Onset of the Next Ovarian Cycle

FSH & LH

corpus luteum regresses

corpus albicans
(12th day after ovulation)

Female Physiology

The Corpus Luteum

A A B B C

corpus luteum 7-8 days 1.5 cm

t
Endoscope images
Development of follicle (A); Graafian follicle (B); rupture scar after ovulation (C,D); corpus luteum after Female Physiology ovulation (E)

corpus albicans 12th day

( day 26 of menses)

D D

E E

Involution of the Corpus Luteum & Onset of the Next Ovarian Cycle

Involution of the corpus luteum

estrogen and progesterone

MENSTRUATION

Female Physiology

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Endometrial histology Menses 14 28 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

Female Physiology

Hormonal changes in the female reproductive system

Ovarian cycle

Uterine cycle

Female Physiology

55

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

Endometrial histology Menses 14 28

Female Physiology

The Monthly Endometrial Cycle and Menstruation

2 Phases
proliferative secretory

Female Physiology

Proliferative Phase (Estrogen Phase)

begins on day 1 of menstruation stroma and epithelial cells
Follicular phase Luteal phase Secretory phase

proliferate rapidly progressive growth of endometrial glands which secrete thin mucus into the cervical canal

Proliferative phase

Female Physiology

Secretory Phase (Progesterone Phase)

occurs after ovulation estrogen: additional cellular proliferation in
Follicular phase Luteal phase Secretory phase

the endometrium progesterone: marked swelling and secretory development of the endometrium

Proliferative phase

Female Physiology

Secretory Phase (Progesterone Phase)

in blood supply PURPOSE: to prepare the
Follicular phase Luteal phase Secretory phase

endometrium for possible implantation of a fertilized ovum

Proliferative phase

Female Physiology

Menstruation
Ovulation LH P4 E2 FSH

2 days before menses (day26): CL regresses: E / P

Luteal phase Secretory phase

Follicular phase

no support to endometrium vasospasm of blood vessels due to prostaglandins

Proliferative phase

Female Physiology

Menstruation
Ovulation LH P4 E2 FSH

endometrial necrosis

slough off from the uterus

Luteal phase Secretory phase

Follicular phase

Proliferative phase

hemorrhage MENSES

Female Physiology

The Menstrual Blood

40 ml of blood loss non-clotting due to fibrinolysin ceases after 4-7 days due to re-epithelialization

Female Physiology

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Endometrial histology Menses 14 28 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

Female Physiology

The Ovarian Steroids Estrogen Progestins

Female Physiology

The Estrogens
Sources:

ovaries placenta adrenal cortex

Female Physiology

3 Types of Estrogens
- estradiol major estrogen produced by
the ovaries

Estrone

majority comes from the peripheral conversion of androgens; some from the ovaries

Estriol
Female Physiology

oxidative product of estradiol and estrone

Progesterone
The most important progestin Sources: ovaries ( 2nd half ) placenta adrenal cortex
Female Physiology

Biosynthesis of Estrogen and Progesterone

Cholesterol P450scc
P450c17 17OHlase 5 pathway DHEA pathway

Acetate

Pregnenolone

4 pathway Progesterone pathway

3-OHSD 5,4 isomerase

17-Hydroxypregnenolone
P450c17, 20 lyase

Progesterone
P450c17 17OHlase

Dehydroepidandrosterone
3-OHSD 5,4 isomerase P450c17 17, 20 lyase

17-Hydroxyprogesterone

Androstenedione P450arom
Female Physiology Estrone

17-OHSD

Testosterone P450arom

17HSD

Estradiol

Graafian follicle showing arrangement of follicle cells around the Oocyte

Hormone production in the graafian follicle
Theca cells Androstenedione
Testosterone

Granulosa cells Corpus luteum

Estrone Estradiol Progesterone

Estrogen

Female Physiology

Follicular Phase of the Ovarian Cycle

Primordial follicle Primary follicle

VESICULAR FOLLICLE accelerated growth in the antral follicle estrogen

(+)

Preantral follicle

granulosa cells
FSH receptors

Antral follicle

FSH + estrogen
vesicular follicle

(+)

LH receptors

LH + estrogen

(+)
growth of theca cells

Female Physiology

OVARIAN STEROIDOGENESIS
Theca cell

Two-cell twogonadotropin hypothesis Compartmentalization of steroid hormone synthesis in the developing follicle
Speroff L, et al. Clinical Gynecologic Endocrinology and Infertilty, ed 6, Lippincott Williams & Wilkins, Baltimore, 1999 F S H L H

Cholesterol

cp450
stenedione
AndrosAndrotenedione

Testosterone

Granulosa cell

AndroTestosterone stenedione
Aromatization Estrone

Estrone Female Physiology

Estradiol

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Endometrial histology Menses 14 28 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

Female Physiology

Biosynthesis of Estrogen and Progesterone

Cholesterol P450scc
P450c17 17OHlase 5 pathway DHEA pathway

Acetate

Pregnenolone

4 pathway Progesterone pathway

3-OHSD 5,4 isomerase

17-Hydroxypregnenolone
P450c17, 20 lyase

Progesterone
P450c17 17OHlase

Dehydroepidandrosterone
3-OHSD 5,4 isomerase P450c17 17, 20 lyase

17-Hydroxyprogesterone

Androstenedione P450arom
Female Physiology Estrone

17-OHSD

Testosterone P450arom

17HSD

Estradiol

Fate of Estrogen and Progesterone

Estrogen Progesterone liver urine liver urine

Female Physiology

Female Hormonal System

Estrogen Development and maturation of the female reproductive organs uterus tubes ovaries
external genitalia
Female Physiology

Female Hormonal System

Estrogen Development and maturation of the secondary female sexual characteristics

Female Physiology

Female Hormonal System

Estrogen Promotes proliferative changes in the uterine endometrium

Female Physiology

Female Hormonal System

Estrogen Extra fat deposition into the subcutaneous tissue of the breasts, buttocks and thighs

Female Physiology

Female Hormonal System

Estrogen Increase skin pigmentation of the nipples, areola and pubic region

Female Physiology

Female Hormonal System

Estrogen Stromal / ductal growth of the breasts

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 Physiology

Female Hormonal System

Estrogen Growth of the ovarian Follicles Production of cervical mucus that is clear, watery, and slightly alkaline
Female Physiology

Female Hormonal System

Estrogen Osteoblastic activity osteoclastic activity At menopause: * osteoclastic activity * bone matrix * deposition of bone calcium and P04Female Physiology

Female Hormonal System

Estrogen Increased protein synthesis in the liver Enhances blood coagulation sodium and water retention
Female Physiology

Female Hormonal System

Progesterone Glandular and secretory development in reproductive organs Lobuloalveolar growth of the breasts

Female Physiology

Female Hormonal System

Progesterone Promotes secretory changes in the uterine endometrium frequency and intensity of the uterine contractions
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 Physiology

Female Hormonal System

Progesterone Production of cervical mucus that is scanty, viscous and acidic Increases the basal body temperature

Female Physiology

Ovulation

MENSTRUAL CYCLE
E2

LH P4

Relative pattern of ovarian, uterine, and hormonal variation along the normal cycle
Palter SF, Olive DL. In Berek JS, et al. Novak s Gynecology, ed 12, Williams and Wilkins, 1996 Endometrial histology Menses 14 28 Ovarian histology Endocrine cycle Follicular phase FSH

Luteal phase

Proliferative phase

Secretory phase

Female Physiology

Control of the Female Hormonal System

(-)

HYPOTHALAMUS GnRH
(+) (-) (+)

ANTERIOR PITUITARY FSH

(-) (+)

(-)

LH
(-)

OVARIES ESTROGEN PROGESTERONE

Female Physiology

INHIBIN