Female reproductive system

Learning objectives

• Name the key hormones secreted by graffian follicles and corpora lutea of the ovaries.

• Describe the physiologic changes that occur in the female reproductive organs during the ovarian and menstrual cycle.

• Know the general actions of 17-estradiol and progesterone.

FEMALE HORMONAL SYSTEM

OOGENESIS

hundred thousand

• When a female child is born, each ovum is surrounded by a single layer of granulosa cells; the ovum, with this granulosa cell sheath, is called a primordial follicle,

• Throughout childhood, the granulosa cells are believed to provide nourishment for the ovum and to secrete an oocyte maturation-inhibiting factor that keeps the ovum suspended in its primordial state in the prophase stage of meiotic division.

• Then, after puberty, when FSH and LH from the anterior pituitary gland begin to be secreted in significant quantities, the ovaries, together with some of the follicles within them, begin to grow.

OVARIAN CYCLE

FEMALE SEXUAL CYCLE

1. FOLLICULAR PHASE

estrogen increases their proliferation and sensitivity to FSH.

FSH is decreasing because of the inhibitory effect of estrogen on FSH release.

Peripheral Actions

Peripheral effects of estrogen produced by the granulosa cells during the follicular phase include

• Circulating estrogens stimulate the female sex accessory organs and sec-ondary sex characteristics.

• Rising levels of estrogens cause the endometrial cells of the uterine mucosal layers to increase their rate of mitotic division (proliferate).

• Circulating estrogens cause the cervical mucus to be thin and watery, making the cervix easy for sperm to traverse

5-10 developingfollicle

progesterone

LH

Proliferative Phase (Estrogen Phase) of the Endometrial Cycle, Occurring Before Ovulation

• The endometrial surface is re epithelialized• Endometrium increases greatly in thickness, owing to

increasing numbers of stromal cells and to progressive growth of the endometrial glands and new blood vessels into the endometrium.

• The endometrial glands, especially those of the cervical region, secrete a thin, stringy mucus.

2 days prior to ovulation

estrogen begins tofall about 1 day before ovulation

Estrogen

FSH

LH removes the restraint upon meiosis, which has been arrestedin prophase for years. The first meiotic division is completed, and the first polarbody is extruded

2 days

Corpus Luteum

• The process of luteinization occurs following the exit of the oocyte from the follicle.

• The corpus luteum is made up of the remaining granulose cells, thecal cells, and supportive tissue.

• Once formed, the luteal cells are stimulated by LH to secrete considerable progesterone and some estrogen. Progesterone inhibits LH

secretion (negative feedback).

The increased plasma level of progesterone has several actions

• It causes the uterine endometrium to become secretory, providing a source of nutrients for the blastocyst.

• It causes the cervical mucus to become thick, sealing off the uterus from further entry of sperm or bacteria.

• It has thermogenic properties, causing the basal body temperature to increase by 0.5–1.0° F.

Secretory Phase (Progestational Phase) of the Endometrial Cycle, Occurring After Ovulation

• Progesterone causes marked swelling and secretory development of the endometrium.

• The glands increase in tortuosity; an excess of secretory substances accumulates in the glandular epithelial cells.

• Also, the cytoplasm of the stromal cells increases; lipid and glycogen deposits increase greatly in the stromal cells;

• Blood supply to the endometrium further increases in proportion to the developing secretory activity.

• Length of the secretory phase is constant – 14 days

Involution of the Corpus Luteum and Onset of the Next OvarianCycle

• Estrogen and progesterone, secreted by the corpus luteum during the luteal phase of the ovarian cycle, have strong feedback effects on the anterior pituitary gland to maintain low secretory rates of both FSH and LH.

• The lutein cells secrete small amounts of the hormone inhibin, inhibits secretion by the anterior pituitary gland, especially FSH secretion

Final involution

• Occurs at the end of almost exactly 12 days of corpus luteum life.

• At this time, the sudden cessation of secretion of estrogen, progesterone, and inhibin by the corpus luteum removes the feedback inhibition of the anterior pituitary gland, allowing it to begin secreting increasing amounts of FSH and LH again.

Monthly endometrial cycle and mensuration

(1) proliferation of the uterine endometrium; (2) development of secretory changes in the

endometrium (3) desquamation of the endometrium, which is

known as menstruation

Proliferative Phase (Estrogen Phase) of the Endometrial Cycle, Occurring Before Ovulation

• The endometrial surface is re epithelialized• Endometrium increases greatly in thickness, owing to

increasing numbers of stromal cells and to progressive growth of the endometrial glands and new blood vessels into the endometrium.

• The endometrial glands, especially those of the cervical region, secrete a thin, stringy mucus.

Secretory Phase (Progestational Phase) of the Endometrial Cycle, Occurring After Ovulation

• Progesterone causes marked swelling and secretory development of the endometrium.

• The glands increase in tortuosity; an excess of secretory substances accumulates in the glandular epithelial cells.

• Also, the cytoplasm of the stromal cells increases; lipid and glycogen deposits increase greatly in the stromal cells;

• Blood supply to the endometrium further increases in proportion to the developing secretory activity.

• Length of the secretory phase is constant – 14 days

Monitoring the Menstrual Cycle

The amount of sex steroids excreted in the urine can be used to monitor the menstrual cycle. For example:• Low progesterone metabolites and low but slowly

rising estrogen metabo-lites characterize the early follicular phase.

• Low progesterone metabolites and rapidly rising estrogen metabolites characterize the latter part of the follicular phase just before ovulation.

• Elevated levels of progesterone metabolites characterize the luteal phase and pregnancy. In the early luteal phase progesterone is rising, in the latter half it is falling.

ABNORMALITIES

pathological

• Anatomic abnormalities • A hypothalamic–pituitary origin-i. Kallman’s syndrome, ii. Functional hypothalamic amenorrhea,iii. Amenorrhea in female athletes, iv. Eating disorders, v. Hypothyroidism, and vi. Pituitary tumors such as prolactinomas.• Ovarian causes –i. Premature ovarian failure (premature meno-pause),ii. Repetitive ovulation failure, oriii. Anovulation (intermittent bleeding), iv. Polycystic ovary.

Polycystic Ovarian Syndrome• One theory suggests that it originates as an

exaggerated adrenarche in obese girls. • The high extraglandular estrogens (mainly

estrone) selectively suppress FSH. Ovarian follicles do have a suppressed aromatase activity and thus a diminished capacity to convert androgen into estrogen, but the adrenals may also contribute to the excess androgens as well.

• High androgens promote atresia in developing follicles and disrupt feedback relationships.

Polycystic Ovarian Syndrome

• The overall result is anovulation-induced amenorrhea with an estrogen-induced endometrial hyperplasia and breakthrough bleeding.

• Characterized by infertility, hirsutism, obesity, insulin resistance, and amenorrhea or oligomenorrhea

Hirsutism

• Defined as an excessive generally male pattern of hair growth.• Virilization refers to accompanying additional alterations, such as

deepening of the voice, clitoromegaly, increased muscle bulk, and breast atrophy.

• It is often associated with conditions of androgen excess such as con-genital adrenal hyperplasia and polycystic ovarian syndrome.

• Axillary and pubic hair are sensitive to low levels of androgen. Hair on the upper chest, face (scalp region not involved), and back requires more androgen and represents the pattern seen in males.

Hirsutism

• Circulating androgens involved are testosterone, DHEA, DHEAS, and androstenedione in response to LH and ACTH.

• Measurements of DHEAS as well as a dexamethasone suppression test helps in separating an adrenal from an ovarian source.

• Polycystic ovarian syndrome is the most common cause of ovarian androgen excess

Menopause

• At age 40 to 50 years, the sexual cycle usually becomes irregular, and ovulation often fails to occur.

• At about age 45 years, only a few primordial follicles remain to be stimulated by FSH and LH, the production of estrogens by the ovaries decreases as the number of primordial follicles approaches zero.

• When estrogen production falls below a critical value, the estrogens can no longer inhibit the production of the gonadotropins FSH and LH.

• FSH and LH ,are produced after menopause in large and continuous quantities.

physiological changes

(1) “hot flushes”(2) psychic sensations of dyspnea(3) irritability, (4) fatigue,(5) anxiety,(6) occasionally various psychotic states, (7)decreased strength and decreased

calcification of bones throughout the body.

Female hormones

OESTROGEN

Functions of the Estrogens—Their Effects on the Primary and

Secondary Female Sex Characteristics

1. Effect of Estrogens on the Uterus and External Female Sex Organs.

• The ovaries, fallopian tubes, uterus, and vagina all increase several times in size. Also, the external genitalia enlarge, with deposition of fat.

• change the vaginal epithelium from a cuboidal into a stratified type

• marked proliferation of the endometrial stroma and greatly increased development of the endometrial glands,

2. Effect of Estrogens on the Fallopian Tubes3. Effect of Estrogens on the Breasts. (1) development of the stromal tissues of the breasts, (2) growth of an extensive ductile system, and (3) deposition of fat in the breasts

4. Effect of Estrogens on the Skeleton inhibit osteoclastic activity in the bones unite the epiphyses with the shafts of the long bones

5. Effect of Estrogens on Protein Deposition slight positive nitrogen balance

6. Effect of Estrogens on Body Metabolism and Fat Deposition.

increase the whole-body metabolic rate fat in the subcutaneous tissues deposition of fat in the buttocks and thighs

7. Effect of Estrogens on the Skin. Soft, smooth vascular

8. Effect of Estrogens on Electrolyte Balance sodium and water retention by the kidney tubules

PROGESTERONE

Effects of progesterone during pregnancy

PHYSIOLOGICAL ACTION

Relative levels of LH release in human females

throughout life.

During the first few years after menopause, follicles timulating hormone (FSH) levels are normally extremely high. A 56-year-old woman completed menopause 3 years ago. However, she is found to have low levels of FSH in her blood. Which of the following is the best explanation for this finding?

A) She has been receiving hormone replacement therapywith estrogen and progesterone since she completedmenopauseB) Her adrenal glands continue to produce estrogenC) Her ovaries continue to secrete estrogenD) She took birth control pills for 20 years beforemenopause

A female athlete who took testosterone-like steroids for several months stopped having normal menstrual cycles. What is the best explanation for this observation?

A) Testosterone stimulates inhibin production fromthe corpus luteumB) Testosterone binds to receptors in the endometrium,resulting in the endometrium’s failure to develop during the

normal cycleC) Testosterone binds to receptors in the anteriorpituitary that stimulate the secretion of folliclestimulatinghormone (FSH) and luteinizing hormone (LH)D) Testosterone inhibits the hypothalamic secretionof gonadotropin-releasing hormone and the pituitarysecretion of LH and FSH

Seven days after ovulation, pituitary secretion of luteinizing hormone (LH) decreases rapidly. What is the cause of this decrease in secretion?

A) The anterior pituitary gland becomes unresponsiveto the stimulatory effect of gonadotropin-releasinghormone (GnRH)B) Estrogen from the developing follicles exerts a feedback

inhibition on the hypothalamusC) The rise in body temperature inhibits hypothalamicrelease of GnRHD) Secretion of estrogen and progesterone by the corpus

luteum suppresses hypothalamic secretion of GnRH and pituitary secretion of LH

E) None of the above

A young woman is given daily injections of a substancebeginning on the 16th day of her normal menstrualcycle and continuing for 3 weeks. As long as the

injections continue, she does not menstruate. The injected substance could be which of the following?

A) TestosteroneB) FSHC) An inhibitor of progesterone’s actionsD) A prostaglandin E2 inhibitorE) HCG

During the 12-hr period preceding ovulation, which of the following is true?

A) The plasma concentration of estrogen is risingB) A surge of luteinizing hormone is secreted fromthe pituitaryC) The surge occurs immediately after the formationof the corpus luteumD) The surge is followed immediately by a fall in theplasma concentration of progesteroneE) The number of developing follicles is increasing

When do progesterone levels rise to their highest point during the female hormonal cycle?

A) Between ovulation and the beginning of menstruation

B) Immediately before ovulationC) When the blood concentration of luteinizing

hormone is at its highest pointD) When 12 primary follicles are developing to theantral stage

As menstruation ends estrogen levels in the blood rise rapidly. What is the source of the estrogen?

A) Corpus luteumB) Developing folliclesC) EndometriumD) Stromal cells of the ovariesE) Anterior pituitary gland

If a woman has a tumor secreting large amounts of estrogen from the adrenal gland, which of the following will occur?

A) Progesterone levels in the blood will be very low

B) Her luteinizing hormone secretion rate will be totally suppressed

C) She will not have normal menstrual cyclesD) Her bones will be normally calcifiedE) All of the above

A 20-year-old woman is not having menstrual cycles.Her plasma progesterone concentration is found to beminimal. What is the explanation for the low level ofprogesterone?

A) LH secretion rate is elevatedB) LH secretion rate is suppressedC) FSH secretion rate is suppressedD) No corpus luteum is presentE) High inhibin concentration in the plasma has

suppressed progesterone synthesis

Before the preovulatory surge in luteinizing hormone, granulosa cells of the follicle secrete which of the following?

A) TestosteroneB) ProgesteroneC) EstrogenD) Inhibin

Two days before the onset of menstruation, secretionsof follicle-stimulating hormone (FSH) and luteinizinghormone (LH) reach their lowest levels.What is the cause of this low level of secretion?

A) The anterior pituitary gland becomes unresponsiveto the stimulatory effect of gonadotropinreleasinghormone (GnRH)B) Estrogen from the developing follicles exerts afeedback inhibition on the hypothalamusC) The rise in body temperature inhibits hypothalamicrelease of GnRHD) Secretion of estrogen, progesterone, and inhibinby the corpus luteum suppresses hypothalamicsecretion of GnRH and pituitary secretion of FSH

What is the cause of menopause?A) Reduced levels of gonadotropic hormones

secretedfrom the anterior pituitary glandB) Reduced responsiveness of the follicles to thestimulatory effects of gonadotropic hormonesC) Reduced rate of secretion of progesterone

from the corpus luteumD) Reduced numbers of follicles available in theovary for stimulation by gonadotropic hormones