Chapter 9. Hormonal Control of Reproduction Part II

Female Reproductive System

Contents

• Part 1. Structure of Ovary

• Part 2. Ovarian Hormones

• Part 3. The Menstrual Cycle

• Part 4. The Endocrinology of Pregnancy

STRUCTURE OF OVARYPart 1

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Structure of Ovary• Fibrous capsule - tunica albuginea• Outer cortex houses developing gametes, the oocytes （卵母细胞） , within follicles （滤泡）

• Inner medulla is loose connective tissue with largest vessels and nerves

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• Follicular phase– 1st approx 14 days but variable– Egg develops in a follicle– Stimulated by FSH– Estrogen produced

• Ovulation– Egg released from follicle (LH surge) – Egg in abdominal cavity– Picked up by fimbria ( 伞部） of fallopian tube

Ovarian Cycle

Ovarian Cycle (cont.)• Luteal phase– Postovulatory phase 14 days (more constant)– Corpus luteum develops from exploded follicle– Produces progesterone as well as estrogen• Progesterone stimulates uterus to be ready for baby

– If no pregnancy, corpus luteum degenerates into corpus albicans

Stages of Follicular Development in the Ovary

OogenesisGeneration of eggs

• Starts in fetal period– No more oocytes made after

about 7th month– Developed only to early stage

of meiosis I by birth and stops (called primary oocyte)

• 6-12 primordial oocytes each cycle selected to develop for ovulation (most die)– Only then is meiosis I

completed– Secondary oocyte is then

arrested in meiosis II• Meiosis II not completed (now

an ovum) unless sperm penetrates its plasma membrane

• Of the 4 daughter cells, only one becomes ovum (needs a lot of cytoplasm)– The other 3 become “polar

bodies”

Primordial Follicle （原始卵泡）

The primordial follicle can be identified by its single layer of follicular cells (red arrow). To the right are two atretic follicles （闭锁卵泡） (blue arrows). Notice the wavy stroma （基质） . Bar = 50 Microns

Primary Follicle（初级卵泡）

At least two layers of follicular cells identify the primary follicle (red arrow). A primordial follicle (in another plane and therefore slightly out of focus) lies alongside (blue arrow). Bar = 50 Microns

Primary Follicle

secondary follicle

The secondary follicle shows the beginning of a fluid-filled space known as the antrum (A). Notice that the oocyte proper (arrow) is embedded within the follicular cells. Bar = 50 Microns

Graafian (vesicular) Follicle

卵丘

卵母细胞

透明带

内膜层

外膜层

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Nearly mature follicle

• Oocyte develops the zona pellucida （透明带）– Glycoprotein coat– Protective shell (egg shell)– Sperm must penetrate to fertilize the oocyte

• Thecal cells stimulated by LH to secrete androgens• Granulosa cells (with FSH influence) convert androgens to

estrogen (follicular cells called granulosa cells now)• Clear liquid gathers to form fluid-filled antrum: now a secondary

follicle• Surrounding coat of granulosa cells: corona radiata （放射冠）• Fully mature, ready to ovulate, called: ”Graafian follicle”

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Ovulation

• Signal for ovulation is LH surge

• Ovarian wall ruptures and egg released– surrounded by its

corona radiata

corpus luteum

Progesterone from the corpus luteum maintains the uterus for implantation. Notice the fullness of the granulosa luteal cells (GL) and positioning of the theca luteal cells (TL). Bar = 50 Microns

corpus luteum

Corpus albicans （白体）

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Fallopian (uterine) tubesFimbriae (fingers) pick up egg

Beating cilia and muscular peristalsis propel egg to uterus

Empties into superior part of uterus*

____Fallopian tubes__

Fimbriae *

Cross section through entire tube

Enlargement of mucosa layer showing ciliated columnar epithelium

PID

Part 2 Hormones Secreted from Ovary

Cases: Imbalanced Sex Steroids• Joanna Jones, 24 years old woman presented with– Increased facial and body hair, acne– Skin greasy– Irregular periods

• Began at the age of 11 years• Always unpreditcable• Miss one or two periods every 3 months since 15 years

– Planning marriage in the next 12 months and hoped to start a family

• Physical Examination– Weighted 85 kg, height 163 cm, body mass index 32kg/cm2

– Hirsutism – Skin: greasy and marked by acne– Fundoscopy, visual fields and eye movement were normal

Imbalanced Sex Steroids

Questions

• What is the differential diagnosis?• Which tests should be performed to confirm

the diagnosis?• How will her symptoms and tests guide

treatment?• Will the couple be infertile?

Secretion of

Progesterone and Estrogen by Ovary

Hypothalamus Pituitary Ovary Axis

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• Pituitary hormones– FSH: follicle stimulating

hormone – LH: luteinizing hormone

• Ovarian hormones– Estrogen– Progesterone

Time: one cycle (approx 28 d.)

*ovulation

Follicular phase Luteal phase

Intracellular Signalling Pathways Activated by Progesterone and Estrogens

Biological Actions of Estrogens and Progesterone

Target Organ

Estrogen Progesterone

Uterus 1. Endometrial thickening2. Make cervical mucus thinner

and more alkaline

1. Increasing vascularization of the endometrium during the luteal phase

2. Make cervical mucus more viscous

Vagina 1. More comified vaginal epithelium

2. Induce synthesis of pheromones’ in vaginal secretion

1. Induces thick mucus secretions from the vaginal epithelium

2. Causes epithelium to thicken and become infiltrated with leukocytes

Breast 1. Promote growth and proliferation of mammary ducts

2. Enlarge breasts at puberty3. Antagonize milk-producing

effect of prolactin

1. Increases growth of breast lobules and alveoli

2. Induces differentiation of ductal tissue

Biological Actions of Estrogens and Progesterone (conti.)

Target Organ

Estrogen Progesterone

Central Nervous System

1. Inhibits FSH secretion2. Brief exposure of the pituitary to

estrogens decreases its sensitivity to GnRH

3. Prolonged exposure of the pituitary to oestrogens increases its sensitivity to GnRH

4. 4. Increase libido possible by direct effect on hypothalamic neurons

5. induce dendrite proliferation in neurons

1. Inhibits secretion of LH2. Cause a rise in body

temperature and is probably responsible for the slight increase in body temperature at time of ovulation

3. Stimulates ventilation and thereby lowers alveolar pCO2 in both the luteal phase of the monthly cycle and in pregnancy

Biological Actions of Estrogens and Progesterone (conti.)

Target Organ

Estrogen Progesterone

Metabolism 1. Exert protein anabolic effect by increasing androgen output from the adrenals

----

Bone and Cartilage

1. Cause epiphysial closure -

Other 1. Partly responsible for female secondary sex characteristics

2. Renal retention of salt and water3. Inhibit atherogenesis by lowering plasma cholesterol,

inhibiting vascular smooth muscle proliferation, and increasing NO synthesis

4. Can promote thrombosis at high levels

Hormonal Regulation of Ovarian Function

• FSH – Stimulates the growth of the

developing follicle– Promote the conversion from

androgen to oestrogen (through aromatase)

• LH – stimulates steroid production

by the corpus luteum and the developing follicle

– stimulate ovulation (LH surge)

Imbalanced Sex Steroids

Differential diagnosisImbalanced sex steroids

• During puberty of the women– breast development - Requires estrogen– pubic hair development - Requires androgens

• Joanna’s symptoms suggest a disruption of the sex steroid: • excess male hormone

– Polycystic ovary syndrome– Androgen secreting ovarian or adrenal tumours– Genetic condition congenital adrenal hyperplasia

• Reduced female hormones– Disease of pituitary/hypothalamus– Ovarian failure

• Which test should be performed to confirm the diagnosis

Section 3. Hormonal Control of the Menstrual Cycle

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The Uterine Wall*• Three basic layers– Perimetrium: outer serous membrane– Myometrium: middle muscle– Endometrium: inner mucosal lining

*

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Endometrium (inner mucosal lining of uterine cavity)

• Simple columnar epithelium containing secretory and ciliated cells

• Lamina propria of connective tissue

2 main layers (Strata)1. Functionalis (functional zone)2. Basalis (basal zone)

(not shed)

(shed if no implantation of baby)

Note:Uterine glandsUterine arteries

Endometrium

• Functional zone – layer closest to the cavity – contains majority of glands – undergoes changes with

monthly cycle• Basal zone – layer just under

myometrium– attaches functional layer to

myometrial tissue– has terminal ends of glands – Remains constant

The Menstrual Cycle ： Menstruation

• Loss of egg and uterine tissue via vagina if fertilization does not occur

The Menstrual Cycle ： Proliferative Phase

• lasts 10 days• FSH & LH

levels increase • egg matures• follicle

secretes estrogen to prepare uterus

The Menstrual Cycle: Ovulation

• High level of estrogen detected by hypothalamus– increased LH– decreased FSH – follicle bursts – egg

released

Estrogens

The Menstrual Cycle: Luteal Phase

• LH converts follicle to corpus luteum – – secretes estrogen

& progesterone. – Progesterone

prepares uterus – Increased

progesterone keeps LH & FSH low

子宫内膜周期性变化

Amenorrhoea• Primary amenorrhoea ： Menarche （初

潮） nerve occurred– Absence of menses by age 16 with normal secondary sexual

characteristics.– Absence of menses by age 14 without secondary sexual development.

• Secondary amenorrhoea– Failure of three or more menstrual periods in

succession in a woman– Cause:

• Pregnancy• Ovarian failure• Pituitary failure• Hypothalamus failure

Hypothalamic Amenorrhea

• Disorder of GnRH secretion, and subsequent failure of FSH and LH secretion

• 1/3 of non-pregnant amenorrhea• Causes– Psychological stress– Anorexia nervosa ( 厌食症） , weight loss– Increased exercise levels– drug-induced amenorrhea – Space-occupying lesion of CNS

Pituitary Amenorrhea

• tumor• Hyperprolactinaemia• Empty sella syndrome ( 空鞍综合征）• Sheehan syndrome ( 席汉氏综合征 )

Ovarian Amenorrhea• Premature ovarian failure

– Ovarian failure occurs before 40 years– Caused by:

• Turner syndrome: absence of one X chromosome• Autoimmune destruction of the ovary

• Polycystic ovarian syndrome– Enlarged ovaries containing numerous cysts– Excessive androgen secretion

Polycystic Ovarian Syndrome

Questions

• What is the differential diagnosis?• Which tests should be performed to confirm

the diagnosis?• How will her symptoms and tests guide

treatment?• Will the couple be infertile?

Section 4 Pregnancy

I. Fertilization and Implantation

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Fertilization

Hormones Changes during Pregnance

• Human Chorionic Gonadotropin (HCG)• Progesterone and Estrogen• Human Chorionic Somatommotropin (HCS)• Relaxin• Aldosterone • Parathyroid hormone (PTH)

Human Chorionic Gonadotropin (HCG)

• Glycoprotein with a molecular weight of 39,000

• Secreted by the syncytial trophoblast cells• can be measured in the blood 8 to 9 days

after ovulation• Function:

• identical to LH in its effect • maintain the corpus letum

Progesterone and Estrogen• Secreted by corpus luteum

before 5-6 weeks of pregancy and by placenta later

• maintain the endometrium and prevent menstruation

• Estrogen: cause enlargement of uterus, breasts and mother’s female external genitalia

• Progesterone: decrease the contractility of pregnant uterus, inhibit release of FSH and LH from anterior pituitary gland (preventing ovulation)

Progesterone and Estrogen

Human Chorionic Somatommotropin (HCS)

• Also called human placental Lactogen (hPL) • Protein with molecular weight of 38,000• Begins to be secreted by the placenta at the 5th week of

pregnancy• Secretion in direct proportion to the weight of placenta.• Function

– stimulates growth of fetus – regulates metabolism of carbohydrate, fat and protein in both the

fetus and the mother– Stimulate mammary gland

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• Relaxin （松弛素） – From placenta, chorion,

and decidua.– Inhibits uterine

contractions and relaxes ligaments of pelvis

– promote cervical ripening

• Aldosterone – From adrenal gland– Increases sodium and

water retention

• Parathyroid hormone (PTH)– Helps maintain high

calcium levels in the blood

Hormonal Changes during Pregnancy (cont.)

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Childbirth

Dilation of cervis; head enters true pelvis

Late dilation with head rotation to AP position

Expulsion: head first safest as is largest part

Delivery of the placenta

Hormones Involved in LaborHormones Involved in Labor

• Labor Initiation:Labor Initiation:• Increasing CRH at the end of the Increasing CRH at the end of the

gestationgestation• the resulting secretion of the resulting secretion of

prostaglandinprostaglandin• Decline of progesteroneDecline of progesterone

• Relaxin, promote cervical ripeningRelaxin, promote cervical ripening