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Physio Endocrinlogy Quiz 1 > Female Reproduction > Flashcards

Female Reproduction Flashcards

1
Q

INTRODUCTION

The adult ovary is a compound organ with the dual function of producing ova and the female sex hormones, estradiol and progesterone. Both hormones play important regulatory roles in the development, growth and maintenance of the various organs that are essential for the continuation of the species. Each ovarian cycle is characterized by the development of a group of follicles, the release of a single ovum, and the development of a corpus luteum that is maintained for a limited period of time. During each cycle the endometrium of the uterus proliferates under the influence of estradiol and progesterone. With the decline of the corpus luteum and the resulting fall in hormone production a new set of follicles develops beginning a new ovarian cycle. The menstrual cycle reflects the cyclic hormonal secretory activity of the ovary preparatory to the implantation of the blastocyst in the uterus. Cyclic ovarian activity, in turn, depends upon the integration of activity between the hypothalamus, hypophysis, and ovary. Thus, ovarian and uterine function is ultimately regulated by the central nervous system via gonadotropin releasing hormone (GnRH). This hormone controls the secretion of pituitary follicle stimulating hormone (FSH) and luteinizing hormone (LH), which in turn stimulate the ovarian production of estradiol and progesterone.

A

INTRODUCTION

The adult ovary is a compound organ with the dual function of producing ova and the female sex hormones, estradiol and progesterone. Both hormones play important regulatory roles in the development, growth and maintenance of the various organs that are essential for the continuation of the species. Each ovarian cycle is characterized by the development of a group of follicles, the release of a single ovum, and the development of a corpus luteum that is maintained for a limited period of time. During each cycle the endometrium of the uterus proliferates under the influence of estradiol and progesterone. With the decline of the corpus luteum and the resulting fall in hormone production a new set of follicles develops beginning a new ovarian cycle. The menstrual cycle reflects the cyclic hormonal secretory activity of the ovary preparatory to the implantation of the blastocyst in the uterus. Cyclic ovarian activity, in turn, depends upon the integration of activity between the hypothalamus, hypophysis, and ovary. Thus, ovarian and uterine function is ultimately regulated by the central nervous system via gonadotropin releasing hormone (GnRH). This hormone controls the secretion of pituitary follicle stimulating hormone (FSH) and luteinizing hormone (LH), which in turn stimulate the ovarian production of estradiol and progesterone.

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2
Q

Is secretion from female gonads necessary to develop female sex organs?

A
  • No secretion from the fetal ovary is necessary for a female phenotype to develop.
  • The male phenotype is determined by hormones from the fetal testis.
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3
Q

Embryology review:

  • Undifferentiated bipotential gonad is the mesonephric kidney system that consists of a mesonephros proper and a Wolffian duct that terminates in the sexually indifferent urogenital sinus.
  • Just prior to differentiation, the Mullerian duct separates from the Wolffian duct and also terminates in the urogenital sinus.
A

Embryology review:

  • Undifferentiated bipotential gonad is the mesonephric kidney system that consists of a mesonephros proper and a Wolffian duct that terminates in the sexually indifferent urogenital sinus.
  • Just prior to differentiation, the Mullerian duct separates from the Wolffian duct and also terminates in the urogenital sinus.
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4
Q

If the undifferentiated gonad develops into an ovary, then:

A
  1. The Wolffian duct atrophies and the Mullerian system develops.
  2. The Mullerian duct becomes the Fallopian tube uterus and part of the vagina.
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5
Q

If the undifferentiated gonad develops into a testis, then:

A
  1. hormones are produced (See male notes) and the Mullerian duct involutes.
  2. The external genitalia develop from the genital tubercle.
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6
Q

What is the genital tubercle? In females what do the genital tubercle become? What do the urethral fold and groove become? What do the genital swellings become?

A
  • The tubercle is a genital fold into which the urogenital sinus empties to the outside.
  • The genital tubercle becomes the lower part of the vagina and clitoris, the urethral fold and groove become the labia minora, and the genital swellings become the labia majora.
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7
Q

Analogy: Sertoli cells are like Granulosa cells. Thecal cells are like Leydig cells. In what hormones activate them, what the cells do, and what the cells produce.

A

Analogy: Sertoli cells are like Granulosa cells. Thecal cells are like Leydig cells. In what hormones activate them, what the cells do, and what the cells produce.

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8
Q

The biological effects of FSH in women are:

A
  1. Stimulates follicle growth and maturation by its action on granulosa cells, but ovulation does not take place.
  2. For follicular growth to occur, FSH must act in synergism with estradiol and LH.
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9
Q

The biological effects of LH in women are?

A
  1. Acts on the preovulatory follicle to cause its rupture and the release of the ovum.
  2. The midcycle surge of LH is essential for ovum maturation and ovulation
  3. LH stimulates the formation and maintenance of the corpus luteum until fertilization of the egg
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10
Q

How is human chorionic gonadotropin similar to LH?

A

• Human chorionic gonadotropin with its intrinsic LH activity rescues the corpus luteum when fertilization occurs and thereby maintains steroid hormone production.

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11
Q

Where are FSH receptors found?

Where are LH receptors found?

A
  • FSH receptors present on granulosa cells
  • LH receptors are located on thecal, interstitial and luteal cells and to varying degrees in granulosa cells.
  • In the granulosa cells, FSH stimulates LH receptor formation.
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12
Q

When does ovulation occur (how many hours after peak E and peak LH levels?)

A
  • Ovulation occurs 24-36 hr after the peak estradiol levels

* 10-12 hr after the LH peak.

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13
Q

What are estradiol levels before and after puberty?

A
  • During childhood, estrogen levels are too low to cause maturation of reproductive tissues.
  • At puberty, the increases in estradiol secretion by the ovary transform female sex organs from immature to adult.
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14
Q

What are the effects of estradiol on the Oviduct?

A

Increases oviduct motility

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15
Q

What are the effects of estradiol on the Uterus?

A
  • Cell proliferation with transformation of epithelium from cuboidal to columnar
  • growth of the endometrial glands
  • increased vascularity
  • increased protein and RNA synthesis
  • Growth of smooth muscle in the uterus.
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16
Q

What are the effects of estradiol on the Cervix?

A
  • Mucus becomes more alkaline and less viscid.
  • Dried cervical mucus assumes a “fern” pattern that disappears once progesterone is produced. (this is a Dx technique to test for ovulation. See Ovutec online)
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17
Q

What are the effects of estradiol on the boobs?

A
  • hypertrophy of the breast with areolar development and pigmentation
  • promote ductal growth.
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18
Q

Estrogens are responsible for the development of the female secondary sex characteristics, Including what?

A
  1. Changes include a rounding of the body contour by the deposition of a layer of subcutaneous adipose tissue in the breasts, buttocks, hips and thighs.
  2. Pubic hair assumes a characteristic triangular pattern that differs from the male (male hair rises to the level of the umbilicus and is in a diamond shape).
  3. The female larynx is small with shorter vocal cords and a resultant higher voice.
  4. Shape of the pelvis. In the female, the inlet assumes a more oval or roundish shape, whereas, in the male, it tends to be spade shaped.
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19
Q

Compare and contrast the effects of E and T on bone growth.

A
  • Both stimulate the closure of the epiphyses of long bones at puberty and terminate linear bone growth.
  • When given to children, androgens stimulate linear bone growth indirectly by their actions on growth hormone.
  • In contrast, estrogens have inhibitory effects on bone growth.
  • Bone growth during puberty in females is mainly due to the actions of adrenal androgens.
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20
Q

What are the effects of progesterone on the endometrium? How is E involved?

A
  • Preparation of the endometrium for implantation of the blastocyst.
  • Stimulates the development, growth and secretory activity of the glands of the endometrium.
  • Most if not all progesterone effects are expressed only after the endometrium has been primed by estrogen.
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21
Q

What are the effects of progesterone on the Oviduct?

A
  • Decreases muscle contractions therefore decreases oviduct motility
  • Tubular block (squeezing of the fallopian tube to hold onto the egg for a day or so while getting the endometrium ready for implantation
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22
Q

What is the effect of P on uterine cells?

A
  • Increases glycogen in uterus to provide nutrients for the blastocyst.
  • Inhibits spontaneous uterine contractions by altering ionic gradients across the myometrial cell membrane and increasing the resting membrane potential.
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23
Q

What is the effect of P on oxytocin receptors?

A
  • P inhibits the estrogen-induced sensitization to oxytocin.

* Removal of “progesterone block” may be a contributing factor to the initiation of parturition.

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24
Q

What is the effect of P on cervical mucus?

A
  • In contrast to estrogen-stimulated mucus, mucus becomes scant, more viscid and infiltrated with lymphocytes.
  • The ferning pattern of dried mucus disappears and mucus becomes resistant to penetration by spermatozoa.
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25
Q

Recap:
What are the effects of E on the Cervix?
What are the effects of P on the cervix?

A
  • E: Mucus becomes more alkaline, less viscid, and more pentrable by sperm
  • P: Mucus becomes scant, more viscid, infiltrated with lymphocytes, and becomes resistant to penetration by sperm.
  • E: produces fern pattern in dried mucus (ovulating)
  • P: produces dot pattern in dried mucus (not ovulating)
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26
Q

What is the effect of P on breast?

A

• progesterone acts with estrogen to induce acinar-lobular development on the previously estrogen stimulated breast.

27
Q

What is the effect of P on sodium levels? P effects on aldosterone and A II?

A
  • natriuretic effect, acting on the distal tubules to cause loss of sodium.
  • Increase in aldosterone excretion and plasma angiotensin II concentration during the luteal phase of the menstrual cycle.
28
Q

What is the structure of an ovary:

A

–Germinal Epithelium
–Cortex: houses the forming gametes or ovarian follicles
–Medulla: contain the largest blood vessels and nerves

29
Q

The ovary produces what two forms of E? Which is more biologically active?
What does the liver and placenta convert these into?

A
  • Estradiol and estrone
  • Estradiol is more active than Estrone
  • Both converted to Estriol in the liver, and by the placenta during pregnancy.
30
Q

Why are Estrogens structurally unique compared to other steroids?

A

• All three estrogens are 18 carbon steroids and are unique because they are the only aromatic (unsaturated A ring) compounds that are synthesized from small acyclic precursors such as acetate.

31
Q

Explain the Two Cell Hypothesis for production of Estradiol in the ovary.

A
  • LH stimulates theca cells to produce androgen (androstenedione)
  • FSH stimulates granulos cells to convert androgen to estradiol (aromatase enzyme)
32
Q

Explain how E is transported in the blood (what proteins are they bound to? What percentage is free?).

A
  • They are transported primarily by albumin.
  • 60% of E is bound to serum albumin
  • 38% of E is bound to testosterone-estradiol-binding globulin (TeBG)
  • 2-3% is free.
33
Q

Explain how P is transported in the blood. (what proteins are they bound to?)

A
  • P and cortisol bind to cortisol binding globulin (CBG) with equal affinity.
  • Since cortisol is 10x higher than that of progesterone, only a small amount of P is bound to CBG.
  • Therefore most P is transported by albumin
  • Free P is biologically active (no percentage given)
34
Q

Recap:

In the blood E is bound to what proteins? P is bound to what proteins?

A
  • Both primarily bound to albumin
  • E is also bound to TeBG, competing with T
  • P is also bound to CBG, competing with cortisol
35
Q

Ovulation correlates with many physical and biochemical measurements including changes in basal body temperature, cervical mucus, vaginal cytology, alkaline phosphatase, and parotid saliva alkaline phosphatase.

A

Ovulation correlates with many physical and biochemical measurements including changes in basal body temperature, cervical mucus, vaginal cytology, alkaline phosphatase, and parotid saliva alkaline phosphatase.

36
Q

Explain the mechanism of ovulation.

A
  • LH surge ==> cAMP rise in the preovulatory follicle ==> oocyte maturation, luteinization of granulosa cells and a parallel increase in production of progesterone and prostaglandins.
  • progesterone ==> collagenase synthesis ==> degrades collagen in follicular wall and formation of a stigma, which is often hemorrhagic.
  • (we used to think that increasing follicular osmotic pressure from synthesis of compounds resulted in ovulation, but recent studies have shown that pressure declines slightly as ovulation approaches).
37
Q

Note: Estrogen has three categorical effects (ie receptors)

A

• cell surface receptors
• Nuclear receptors ER alpha and ER beta
• Indirect production of other hormones that cause effects
Note: ERalpha and ERbeta only have 20% similar effects. They are very different. This has chemotherapy importance.

38
Q

Mechanism of Hormone Action of E and P (ie, receptors and actions)

A

• similar to all steroid hormones, except that E also has cell surface receptors
• Details follow if you want to read them:
Estradiol, like the other steroid hormones, binds to receptors on the cell membrane and in the nucleus. Following binding of steroid to receptors, a conformational change occurs and the receptor complex binds to the nucleus (nonhistone proteins and DNA) to stimulate RNA polymerase, chromatin template activity, synthesis of all classes of RNA’s as well as replication of DNA followed by cell division.

39
Q

In what tissues are P receptors found? How is P receptor expression affected by E?

A
  • P receptors in the uterus and other tissues of the body.

* Progesterone receptor expression increases with estrogen stimulation.

40
Q

How do E and P affect uterine fibroblasts?

A

• act indirectly through receptors in uterine fibroblasts (ie, uterine fibroblasts secrete other compounds in response to E and P and these other compounds have biological effect)

41
Q

What is Hepatocyte Growth Factor and its relation to estrogen?

A
  • made by uterine fibroblasts in response to estradiol stimulation
  • stimulates epithelial cell growth, morphogenesis, migration, and motility of uterus
42
Q

What is TGFbeta and its relation to estrogen?

A
  • made by uterine epithelial cells in response to estradiol

* regulates NK cell activity and antigen presentation by macrophages and dendritic cells in the reproductive tract

43
Q

In addition to steroid hormones, what three gonadal protein hormones DO modulate FSH release, but DO NOT modulate LH release.

A

Activin
Inhibin
Follistatin

44
Q

What is Activin?

A
  • stimulates FSH
  • a homodimer consisting of two inhibin β-chains
  • highly potent in stimulating the release of FSH but not LH or any other pituitary hormone
45
Q

What is Inhibin?

A
  • aka folliculostatin
  • found in the follicular fluid.
  • Synthesized by granulosa cells
  • selectively suppresses the secretion of FSH but not LH.
46
Q

What is Follistatin?

A
  • secreted by the developing follicle also suppresses FSH.
  • As a single chain glycosylated polypeptide
  • NOT a member of the inhibin family
  • selectively decreases the levels of FSH mRNA and inhibits FSH secretion
47
Q

Explain the decline of FSH during the follicular phase of the menstrual cycle.

A

• negative feedback of estradiol, inhibin and follistatin secreted by the developing follicle.

48
Q

When is inhibin and inhibin activity highest?

A
  • higher in follicular phase than the luteal phase

* there is a progressive increase in intrafollicular inhibin during the course of follicular maturation.

49
Q

Recap:
Negative Feedback of FSH comes from:
Positive Feedback of FSH (and LH) comes from:

A
  • Neg: Inhibin (Folliculostatin) and Follistatin

* Pos: Estradiol and Activin (Note: E stimulates GnRH in hypothal and both FSH and LH )

50
Q

FYI, Do not need to learn: Nonsteroidal Factors Produced by the Ovary that Regulate
Endocrine-Autocrine and -Paracrine Ovarian Function

 Activin
Adenosine
Angiogenic factors
Catecholamines
Eicosanoids
Follicular-regulating protein
Follistatin
FSH-binding inhibitor
LHRH-like molecules
Growth factors:
Epidermal growth factor
Fibroblast growth factor
Insulin-like growth factors
Platelet-derived growth factor
Transforming growth factors (a and b) 
Inhibin
LH-binding inhibitor
Luteinization stimulator
Antimullerian hormone
Oocyte maturation inhibitor
Oxytocin
Pro-opiomelanocortin-derived peptides
Relaxin
Renin-angiotensin
A

FYI, Do not need to learn: Nonsteroidal Factors Produced by the Ovary that Regulate
Endocrine-Autocrine and -Paracrine Ovarian Function

 Activin
Adenosine
Angiogenic factors
Catecholamines
Eicosanoids
Follicular-regulating protein
Follistatin
FSH-binding inhibitor
LHRH-like molecules
Growth factors:
Epidermal growth factor
Fibroblast growth factor
Insulin-like growth factors
Platelet-derived growth factor
Transforming growth factors (a and b) 
Inhibin
LH-binding inhibitor
Luteinization stimulator
Antimullerian hormone
Oocyte maturation inhibitor
Oxytocin
Pro-opiomelanocortin-derived peptides
Relaxin
Renin-angiotensin
51
Q

Menstrual Cycle. By convention, the first day of menstrual bleeding is cycle day one, and all subsequent days are numbered serially until the next menstrual bleeding. Although the mean cycle length is 28 - 29 days, cycle lengths between 21 and 35 days are normal. Each menstrual cycle is divided into proliferative, midcycle and secretory phases.

A

Menstrual Cycle. By convention, the first day of menstrual bleeding is cycle day one, and all subsequent days are numbered serially until the next menstrual bleeding. Although the mean cycle length is 28 - 29 days, cycle lengths between 21 and 35 days are normal. Each menstrual cycle is divided into proliferative, midcycle and secretory phases.

52
Q

When is the Proliferative phase? Midcycle? Secretory phase?

A
  • Proliferative is between the first day of menses and the day of ovulation.
  • Midcycle is the time interval around ovulation.
  • The secretory phase extends from ovulation to the start of menstruation.
53
Q

Name the events of the menstrual cycle. See ppt for schemata of the numbers listed below.

A
  1. Just prior to the onset of menses, blood levels of FSH rise, stimulating the gradual maturation of a new set of follicles. Increased levels of FSH and activin, which augments FSH, lead to an increase in estradiol secretion by granulosa cells.
  2. Estradiol produced by a maturing follicle increases FSH receptor expression and causes that follicle to be more responsive to FSH. This synergistic relationship between FSH and estradiol is an intraovarian-positive autoregulatory feedback mechanism that is responsible for the rapid follicular growth.
  3. As the follicular phase progresses, estradiol along with inhibin and follistatin, produced by granulosa cells, feed back negatively to inhibit pituitary FSH.
  4. As the follicle matures, estradiol levels in blood rise to a critical concentration at which, estradiol feedback on the hypothalamus and pituitary turns from negative to positive and GnRH is released.
  5. GnRH in turn stimulates the pituitary surge of LH and FSH that initiates ovulation. Prior to ovulation, there is a detectable increase in plasma progesterone. Progesterone acts in synchrony with LH to initiate follicular rupture.
  6. When the follicle ruptures, the ovum with its surrounding layer of granulosa cells is released. Remaining granulosa cells in the follicle in response to LH become the corpus luteum that secretes progesterone and some estradiol. Both progesterone and estradiol act at the hypothalamus and pituitary to suppress luteal phase FSH and LH.
  7. Maturation of the corpus luteum is reached in 8 to 9 days after which regression occurs if fertilization has not occurred. As the corpus luteum regresses, plasma estrogens and progesterone decrease.
  8. The beginning of a new menstrual cycle is signaled by increased secretion of pituitary FSH ; this increase is the result of the removal of the negative feedback of estrogen and progesterone on the hypothalamus.
54
Q

What is the Implantation Window? When does it occur? How long does it last?

A
  • that period when the uterus is receptive for implantation of the free-lying blastocyst.
  • It occurs about 5-7 days after the LH peak (surge) at midcycle and lasts about 4 days.
  • It is at this time that the blastocyst is immobilized as a result of contact with the endometrium
55
Q

What is the Window of Vulnerability? How long does it last? Why is it here?

A
  • 7- to 10-day interval lasting from ovulation into the secretory phase of the cycle when the immune protection is partially suppressed, making it more likely for women to be infected sexually transmitted diseases including HIV.
  • Suppression by the endocrine system prevents the immune system from attacking sperm and the fertilized egg, both of which are allogeneic.
56
Q

Where and which are adaptive immune cells located in the cervix and vagina? Where and which are they located in the uterus? How do their numbers vary during the menstrual cycle? (I think we just need to know the general principles and not the details)

A
  • In the cervix and vagina, CD4+ and CD8+ T cells are distributed throughout the stroma
  • In the uterus, these cells form lymphoid aggregates, consisting of a B cell core surrounded by CD4+ or CD8+ T cells with a halo of macrophages.
  • Aggregates vary in size with stage of the menstrual cycle: proliferative phase (300-400 cells) vs secretory phase (3000-4000 cells).
57
Q

During the Secretory phase, immune suppression takes place in which parts of the female genitals (ie uterus, cervix, vagina)? What cells of the immune system are suppressed?

A

• suppression in the uterus, but not the vagina
• suppression of cytotoxic T lymphocytes (CTL)
o which kill cancer cells
o infected cells
o allogeneic cells (blastocyst).

58
Q

During the midcycle phase, immune suppression takes place in which parts of the female genitals (ie uterus vs vagina)?

A
  • Suppression of cervical-vaginal of

* cytokines, chemokines, and antimicrobials secretions.

59
Q

Explain the steps of fertilization.

A
  • The acrosome, releases enzymes that penetrate the Zona Pelucida (outer egg membrane).
  • The egg cell membrane changes its electrical characteristics.
  • This electrical signal causes release of cortical granules into the Perivitelline space (space between egg and Zona Pelucida).
  • The Perivitelline Space swells preventing other sperm from entering
  • This process is called the Cortical Reaction
  • Depolarization caused by sperm penetration results in one last round of division in the egg’s nucleus, forming a pronucleus containing one set of genetic information.
  • The pronucleus from the egg merges with the nucleus from the sperm. Once the
  • two pronuclei merge, cell division begins.
60
Q

What is the Cortical Reaction in fertilization?

A

• The process by which the egg seals itself from being penetrated by a second sperm.

61
Q

After fertilization, the nuclei of the sperm and egg fuse to form a new cell (the zygote) that contains 46 chromosomes, 23 from each parent cell. As the zygote travels to the uterus, it divides, forming a cluster of cells (the morula) at about 3 days after fertilization. The morula develops a cavity and is now known as a blastocyst, which will become the embryo. This blastocyst floats freely within the uterine cavity for about 48hr before attaching itself to the uterine lining. About 10 days following fertilization, the blastocyst is completely imbedded into the endometrium, and forms the placenta.

A

After fertilization, the nuclei of the sperm and egg fuse to form a new cell (the zygote) that contains 46 chromosomes, 23 from each parent cell. As the zygote travels to the uterus, it divides, forming a cluster of cells (the morula) at about 3 days after fertilization. The morula develops a cavity and is now known as a blastocyst, which will become the embryo. This blastocyst floats freely within the uterine cavity for about 48hr before attaching itself to the uterine lining. About 10 days following fertilization, the blastocyst is completely imbedded into the endometrium, and forms the placenta.

62
Q

What does prolactin do in females?

A
  • Stimulates milk production by mammary gland

* Helps to maintain Corpus Luteum (in rats)

63
Q

What does Oxytocin to in females?

A
  • Milk letdown

* Uterine contractions during labor

Physio Endocrinlogy Quiz 1 (6 decks)

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