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7.8. Female sexual endocrinology. Flashcards

1
Q

I. Anatomy of female gonads (just take a look)
1. What are the features of female gonads?

A
  • The female gonads are the ovaries, and these are connected to the uterus via the fallopian tubes.
  • In the ovary there is a cortex, medulla, and hilum.
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2
Q

I. Anatomy of female gonads (just take a look)
2. What are the structures in female ovary?

A
  • In the ovary there is a cortex, medulla, and hilum.
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3
Q

I. Anatomy of female gonads (just take a look)
3. What is the cortex of ovary lined with? What is the function?

A
  • The cortex is lined with germinal epithelium and the female’s oocytes – each egg within its own follicle.
  • The dominant follicle is the site of steroid hormone synthesis, which can be paracrine or endocrine in function.
    => Both functions act to support the ova development and potential fertilization, as well as acting on tissues such as the breasts, uterus, and bones (increases OPG activity => resulting in bone formation)
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4
Q

II. Cyclic reproductive function – menstrual cycle
1. What are the main features of Cyclic reproductive function – menstrual cycle?

A
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5
Q

II. Cyclic reproductive function – menstrual cycle
2A. What are the phases of ovarian cycle?

A

I – Follicular phase
- Development of follicles stimulated by FSH
- Rise in ovarian [estradiol] triggers a LH surge, which causes ovulation
- Duration is quite variable (~14 days)

II – Luteal phase
- Follicle transforms into a corpus luteum
- Length of this phase is constant = 14 days
- w/o pregnancy, the corpus luteum dies -> menses

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6
Q

II. Cyclic reproductive function – menstrual cycle
2B. What happen in follicular phase of ovarian cycle?

A
  • Development of follicles stimulated by FSH
  • Rise in ovarian [estradiol] triggers a LH surge, which causes ovulation
  • Duration is quite variable (~14 days)
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7
Q

II. Cyclic reproductive function – menstrual cycle
2C. What happen in Luteal phase of ovarian cycle?

A
  • Follicle transforms into a corpus luteum
  • Length of this phase is constant = 14 days
  • w/o pregnancy, the corpus luteum dies -> menses
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8
Q

II. Cyclic reproductive function – menstrual cycle
3A. What are 3 phases of endometrial cycle?

A

I – Menses
II – Proliferative phase
III – Secretory phase

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9
Q

II. Cyclic reproductive function – menstrual cycle
3B. In endometrial cycle,
what happen in I – Menses?

A
  • 2 to 6 days
  • Marked by menstrual bleeding
    => decline of estrogen and progesterone levels; the endometrial functional layer will be destroyed
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10
Q

II. Cyclic reproductive function – menstrual cycle
3C. In endometrial cycle,
what happen in II – Proliferative phase?

A
  • Endometrium proliferates thanks to progesterone
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11
Q

II. Cyclic reproductive function – menstrual cycle
3D. In endometrial cycle,
what happen in III – Secretory phase?

A
  • Stroma cells of endometrium enlarge and become more eosinophilic – necessary during pregnancy
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12
Q

III. Ovarian hormone synthesis
1. What happen during Ovarian hormone synthesis?

A
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13
Q

III. Ovarian hormone synthesis
2. How is free cholesterol transferred into the mitochondrial matrix?

A
  • Free cholesterol is transferred into the mitochondrial matrix in a steroidogenic acute regulatory (StAR) protein dependent manner
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14
Q

III. Ovarian hormone synthesis
3. What happen during Androgen production in the ovary?

A
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15
Q

IV. Regulation of Ovarian hormone synthesis
1. What happen in Regulation of Ovarian hormone synthesis?

A
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16
Q

IV. Regulation of Ovarian hormone synthesis
2. What is the first important hormone produced in Regulation of Ovarian hormone synthesis?

A
  • Neurons in the arcuate nucleus and the pre-optic area of the HT secrete GnRH
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17
Q

IV. Regulation of Ovarian hormone synthesis
3. What is the molecular mechanism of GnRH?

A
  • GnRH binds to Gq-coupled receptors on the gonadotroph membrane, which cause the release of the gonadotropic cells (LH + FSH)
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18
Q

IV. Regulation of Ovarian hormone synthesis
4. What is the role of gonadotropic
cells (LH + FSH)?

A
  • LH binds to receptors (Gs) on theca cells
  • FSH binds to receptors (Gs) on granulosa cells
    +) PKA stimulates synthesis of enzymes: activins + inhibins
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19
Q

IV. Regulation of Ovarian hormone synthesis
5. The role of activins and inhibins

A
  • FSH binds to receptors (Gs) on granulosa cells
    => PKA stimulates synthesis of enzymes: activins + inhibins
  • The activins and inhibins feed back only on FSH production by the anterior pituitary
    +) Activin = positive feedback, inhibin = negative feedback
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20
Q

IV. Regulation of Ovarian hormone synthesis
6. The role of The estrogens and progestins in hormone synthesis regulation

A
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21
Q

IV. Regulation of Ovarian hormone synthesis
7. What is the consequence of High level of estradiol (during the late follicular phase)

A

High level of estradiol (during the late follicular phase) enhances the sensitivity of gonadotrophs to GnRH

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22
Q

IV. Regulation of Ovarian hormone synthesis
8. What are the hormones regulate LH + FSH production?

A

CRH, β-endorphin, PRL and leptin/ghrelin regulate LH + FSH production

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23
Q

IV. Regulation of Ovarian hormone synthesis
9. Make a schematic diagram of Regulation of Ovarian hormone synthesis

A
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24
Q

V. Regulation of gonadotropin synthesis
1. What happen in Regulation of gonadotropin synthesis?

A
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25
Q

V. Regulation of gonadotropin synthesis
2. What happen after Binding of GnRH to the receptor?

A

Binding of GnRH to the receptor on the gonadotrophic membrane activates the PLC pathway:
Gq -> ↑PLC
-> IP3 -> ↑[Ca2+]IC
=> LH + FSH release

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26
Q

V. Regulation of gonadotropin synthesis
3. What is the role of PKC in Regulation of gonadotropin synthesis?

A
  • PKC stimulates gene transcription and synthesis of gonadotropins (LH + FSH) by phosphorylation
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27
Q

V. Regulation of gonadotropin synthesis
4. What is the role of estradiol In the late follicular phase?

A

In the late follicular phase, estradiol enhances the GnRH sensitivity in the anterior pituitary, which causes a much larger release of LH

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28
Q

VI. Oocyte maturation
1. What are the events in Oocyte maturation?

A
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29
Q

VI. Oocyte maturation
2. What does Primordial germ develop into?

A

Primordial germ cells develop into oogonia
-> oogonia undergo mitotic divisions
-> some enter meiosis 1 and become primary oocytes

(- Meiosis 1 arrest at prophase 1 (initially, this arrest is caused by the lack of proteins required for meiosis 1 to occur – later, higher levels of cAMP maintains arrest))

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30
Q

VI. Oocyte maturation
3. How does Primordial follicles form?

A

Primordial follicles form when primary oocytes are surrounded by pre-granulosa cells

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31
Q

VI. Oocyte maturation
4. What happen when Primary follicles form?

A

Primary follicles form granulosa cells (cuboidal)
- Zona pellucida formscontains ZP1, 2, 3 (proteins)
- Number of FSH receptors on the granulosa cells increase

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32
Q

VI. Oocyte maturation
5. What happen when secondary follicles form?

A
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33
Q

VI. Oocyte maturation
6. What happen when Tertiary (antral) follicles form?

A

antrum develops within
(fluid-filled space)

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34
Q

VI. Oocyte maturation
7. What are the 3 types of Granulosa cells of the tertiary and Graafian follicle?

A
  1. Mural granulosa cells:
    - farthest away from oocyte, most
    metabolically active, large quantities of LH receptors
  2. Cumulus granulosa cells (cumulus oophorus):
    - innermost = corona radiata, shed with oocyte upon ovulation
  3. Antral granulosa cells:
    - faces the antrum, after ovulation they become luteal cells
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35
Q

VI. Oocyte maturation
7B. What are the features of Mural granulosa cells

A

farthest away from oocyte, most
metabolically active, large quantities of LH receptors

36
Q

VI. Oocyte maturation
7C. What are the features of Cumulus granulosa cells?

A

Cumulus granulosa cells (cumulus oophorus): innermost
= corona radiata, shed with oocyte upon ovulation

37
Q

VI. Oocyte maturation
7C. What are the features of Antral granulosa cells?

A

faces the antrum, after ovulation they become luteal cells

38
Q

VI. Oocyte maturation
8. A few hours before ovulation, what happen to primary oocyte? What is the molecular mechanism?

39
Q

VI. Oocyte maturation
9. A few hours before ovulation, primary oocyte completes meiosis 1 due to LH surge
=> Make a schematic diagram to demonstrate this

A

A few hours before ovulation, primary oocyte completes meiosis 1 due to LH surge
- LH surge inhibits inhibitory effects of the cGMP on the PDE (disinhibition) -> ↓cAMP -> meiotic resumption
- MAPK pathway proteins arrest meiosis at metaphase 2meiosis 2 completed upon fertilization

40
Q

VI. Oocyte maturation
10. What is dominant follicle?

A

The one that has the most FSH receptors remaining = dominant follicle

41
Q

VII. Steroidogenesis in the dominant follicle
1. What are the 2 types of cells participating in Steroidogenesis in the dominant follicle?

A
  1. Theca cells
  2. Mural granulosa cells
42
Q

VII. Steroidogenesis in the dominant follicle
2A. What are the features of theca cells?

43
Q

VII. Steroidogenesis in the dominant follicle
2B. What are the effects of LH on theca cells?

44
Q

VII. Steroidogenesis in the dominant follicle
3. What are the featues of mural granulosa cells

45
Q

VIII. Ovulation
1. What are the 5 steps of ovulation?

46
Q

VIII. Ovulation
2. What happen prior to ovulation?

A

Prior to ovulation, the large pre-ovulatory follicle presses against the ovarian surface and generates a stigma ( a poorly vascularized bulge)

47
Q

VIII. Ovulation
3. What is the consequence of LH surge?

A

LH surge induces release of inflammatory cytokines and
hydrolytic enzymes from theca + granulosa cells
=> these enzymes break down the follicle wall, tunica albuginea and surface epithelium

48
Q

IX. Corpus luteum
1. What happen after ovulation?

49
Q

IX. Corpus luteum
2. What is Regression of corpus luteum involved?

A
  • Regression of corpus luteum appears to involve release of prostaglandin (PGF2α) from both the lutein cells and the uterus
50
Q

IX. Corpus luteum
3. What will Corpus luteum turn into?

A
  • Corpus luteum ultimately turns into corpus albicans (scar), and it is later absorbed
    => If pregnancy occurs, hCG is released by syncytiotrophoblasts and maintains corpus luteum
51
Q

IX. Corpus luteum
4A. What happen during Steroidogenesis in the corpus luteum?

52
Q

IX. Corpus luteum
4B. What is the role of Theca lutein cells?

A

Uptake of cholesterol and induce production of androstenedione
=> will diffuse into the granulosa cell and produce estradiol-17β

53
Q

IX. Corpus luteum
4C. What is the role of Granulosa lutein cells?

A

Uptake of cholesterol
-> pregnenolone
-> progesterone (LH signal) + estradiol

54
Q

X. Ovarian cycle - Follicular phase
1. What happen at the end of luteal phase?

55
Q

X. Ovarian cycle - Follicular phase
2A. What happen at the Start of follicular phase?

56
Q

X. Ovarian cycle - Follicular phase
2B. At the start of Follicular phase, what will FSH do?

A
  • FSH will recruit preantral follicles
    => 20 antral follicles are recruited
57
Q

X. Ovarian cycle - Follicular phase
2C. At the start of Follicular phase, what is the fate of follicles?

A
  • Follicles will mature into dominant follicles and produce more estrogen (granulosa cells)
    => [estradiol] is below 200pg/mL = threshold (+)-feedback of LH + FSH
58
Q

X. Ovarian cycle - Follicular phase
2D. At the start of Follicular phase, what is the role of Estradiol + inhibin?

A

Estradiol + inhibin will have an inhibitory effect on FSH production
- Only those follicles will keep developing, which express enough FSH receptors
- Only 1 dominant follicle will be selected
Will produce a huge amount of estradiol (peak) and inhibin ( => FSH production↓)

59
Q

X. Ovarian cycle - Follicular phase
2E. At the start of Follicular phase, what happen When estradiol production exceeds 200pg/mL?

A
  • When estradiol production exceeds 200pg/mL, it will indue (+)-feedback for LH production (+ a little bit for FSH as well)
    => rapid ↑ in LH production before ovulation (peak of estradiol is PRIOR to the peak of LH)
60
Q

X. Ovarian cycle
3. What happen during Ovulation?

A
  • Luteinization takes place
    -> progesterone production↑ + estradiol production↑
    -> (+)-feedback to LH production is reduced
    => ending of LH surge after ovulation
61
Q

X. Ovarian cycle
4A. What happen during luteal phase?

62
Q

X. Ovarian cycle
4B. What will corpus luteum do during luteal phase?

A

produces high amount of progesterone and estrogen (+ inhibin)

63
Q

XI. Endometrial cycle
1. What happen during Proliferative phase?

64
Q

XI. Endometrial cycle
2. What is the role of estrogen during proliferative phase?

A
  • Proliferation and differentiation of the endometrium stimulated by estrogen secreted by developing follicles -> endometrial glands formed, covered with secretory epithelial cells
    => Estrogen induces the synthesis of growth factors, which causes the development of components of the endometrium = IGF, TGF, EGF
65
Q

XI. Endometrial cycle
3. What is the consequence of the increase in progestin receptor expression during proliferative phase?

A
  • Myometrium: ↑sensitivity to oxytocin receptor induced by estrogen
  • Body temperature slightly decreases before ovulation
66
Q

XI. Endometrial cycle
4A. What happen during Secretory phase?

67
Q

XI. Endometrial cycle - Secretory phase
4B. What happen in early secretory phase?

A

Early secretory phase: development of nucleolar channel system

68
Q

XI. Endometrial cycle - Secretory phase
4C. What happen in Middle-late secretory phase?

A
  • Pre-decidualization: enlargement of stromal cells
  • ↑ vascularization of the endometrium
  • ↑ secretory capacity of the endometrial glands
  • Functional layer of the endometrium form
    => Zona compacta: upper (less glandular) layer
    => Zona spongiosa: lower (more glandular) layer
69
Q

XI. Endometrial cycle
5A. What happen during menstrual phase?

70
Q

XI. Endometrial cycle
5B. What do cells produce during menstrual phase?

A
  • Cells start to produce PGF2α and matrix metalloproteases
71
Q

XII. Effects of estrogen
1. What are the 6 effects of estrogen?

A
  1. Bone formation
  2. Liver
  3. Cardiovascular
  4. Integument (skin)
  5. Adipose tissue
  6. CNS
72
Q

XII. Effects of estrogen
2. What is the effect of estrogen on Bone formation?

A
  • Promotes the survival of osteoblasts, apoptosis of osteoclasts, closure of epiphyseal plate
  • Calciotropic, intestinal absorption of Ca2+
73
Q

XII. Effects of estrogen
3. What is the effect of estrogen on Liver?

A
  • LDL receptor↑
  • Circulating HDL↑
  • CBG, TBG, SHBG↑
74
Q

XII. Effects of estrogen
4. What is the effect of estrogen on Cardiovascular?

75
Q

XII. Effects of estrogen
5. What is the effect of estrogen on Integument (skin)?

A
  • Proliferation of keratinocytes
  • Collagen synthesis (with progesterone, by inhibiting matrix metalloproteinases)
  • Glycosaminoglycan – wound healing
76
Q

XII. Effects of estrogen
6. What is the effect of estrogen on Adipose tissue?

A

Adipose tissue: LPL↓, HLP↓
=> lipolysis↑ (long-run)

77
Q

XII. Effects of estrogen
7. What is the effect of estrogen on CNS?

A

neuroprotection

78
Q

XIII. What are the Effects of progesterone?

A
  • Setpoint of thermoregulation (↑body temperature during ovulation)
  • Pre-menstrual dysphoria (rapid drop in progesterone = mood change)
  • Sensitize ventilation response to PCO2
79
Q

XIV. Transport and metabolism of estrogen and progesterone
1. How is estrogen transported? (give %)

A
  • Free = 2-3%
  • Bound: albumin = 60% + SHBG = 38%
80
Q

XIV. Transport and metabolism of estrogen and progesterone
1. How is Progesterone transported? (give %)

A
  • Free = 2-3%
  • Bound: albumin = 80% + CBG = 18% (corticosteroid binding globulin)
81
Q

XV. Sexual intercourse of the female
1. What is the neural pathway of Sexual intercourse of the female?

A

Afferentation is through sacral somatosensory fibers

82
Q

XVI. Menopause
1. What is Menopause?

A
  • Termination of reproductive function in women
  • Menstruation comes to an end (only a few functional follicles remain the ovaries)
83
Q

XVI. Menopause
2. What is the molecular mechanism of menopause?

A
  • ↓estradiol and progesterone production (mood changes)
  • Lack of (-)-feedback: LH + FSH levels may be higher due to an increased GnRH production
84
Q

XVI. Menopause
3. What are the symptoms of Menopausal syndrome?

A

Menopausal syndrome: hot flashes, night sweats, mood changes, loss of libido

85
Q

XVI. Menopause
4. What are the physical changes due to menopause?

A

Physical changes: atrophy of the vaginal epithelium, osteoporosis, ↓vaginal
secretions

A Physiology (88 decks)

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