Lectures 5 & 6 - Female Reproduction -Jan 17 & 20, 2025 Flashcards
(116 cards)
1
Q
What does the cortex of the ovary contain?
A
Developing follicles and corpus luteum at various stages of development
The cortex also includes stroma, which is connective tissue, interstitial cells, and blood vessels.
2
Q
What are the two main components of the ovary?
A
Inner medulla and outer cortex
The cortex surrounds the medulla except at the hilus.
3
Q
What are the stages of follicle maturation?
A
Primordial, graafian (or preovulatory) follicles
4
Q
When do LH and FSH levels peak during a female’s life?
A
During fetal life and again during early infancy
5
Q
What happens to LH and FSH levels at the onset of puberty?
A
They slowly rise and begin to oscillate at regular monthly intervals.
6
Q
What occurs to gonadotropin levels at menopause?
A
They rise to very high levels.
7
Q
True or False: GnRH secretion during puberty is continuous.
A
False
8
Q
What happens to the sensitivity of gonadotrophs to feedback inhibition by estrogens during puberty?
A
It decreases.
9
Q
Fill in the blank: During maturation, the sensitivity of the hypothalamic-pituitary system to inhibition by sex steroids falls to reach the ______ level characteristic of the adult.
A
low
10
Q
What characterizes the release of GnRH?
A
It is released in bursts about once per hour.
11
Q
What is the half-life of GnRH in blood?
A
2 to 4 minutes
12
Q
In the early follicular phase, what is the gonadotrophs’ sensitivity to GnRH?
A
Not very sensitive
13
Q
What happens to gonadotroph sensitivity as the follicular phase progresses?
A
It becomes much more sensitive to GnRH.
14
Q
Where is the pulse generator for GnRH located?
A
In the arcuate nucleus of the medial basal hypothalamus.
15
Q
What is the role of the hypothalamic-pituitary-ovarian axis?
A
It drives the menstrual cycle.
16
Q
What hormones do gonadotrophs synthesize and release?
A
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
17
Q
What do the ovaries produce besides sex steroids?
A
Peptides called inhibins and activins.
18
Q
How do ovarian steroids and peptides affect the hypothalamus and anterior pituitary?
A
They exert both negative and positive feedback.
19
Q
What happens at the end of the follicular phase regarding estrogen levels?
A
They rise, leading to positive feedback on the hypothalamic-pituitary axis.
20
Q
Fill in the blank: GnRH binds to a G-protein-coupled receptor on the gonadotroph membrane, triggering the ______ pathway.
A
IP3/DAG
21
Q
What is the effect of GnRH on gonadotrophin release?
A
It stimulates the synthesis and release of FSH and LH.
22
Q
What is the structure of FSH and LH?
A
Glycoprotein heterodimers comprising common α-subunits and unique β-subunits.
23
Q
What does the rise in intracellular calcium ([Ca2+]i) trigger?
A
Exocytosis and gonadotropin release.
24
Q
What is receptor replenishment?
A
The phenomenon where a portion of the GnRH receptor is shuttled back to the cell surface.
25
What type of feedback do ovarian steroids provide during most of the menstrual cycle?
Negative feedback
26
What is a manifestation of positive feedback by estrogens at the end of the follicular phase?
Increased sensitivity of gonadotrophs to GnRH.
27
What is the role of estrogens in the feedback mechanism of the hypothalamic-pituitary axis?
Estrogens feed back positively on the axis, increasing the sensitivity of gonadotrophs in the anterior pituitary gland to GnRH.
28
What effect do estrogens have on gonadotrophs in the absence of estrogen?
Pituitary cells cultured in the absence of estrogen have suboptimal responses to GnRH.
29
What is the role of progesterone during the late follicular phase?
Rising levels of progesterone produce a positive feedback response and facilitate the LH surge.
30
What type of feedback do estrogens and progestins exert on the hypothalamus and anterior pituitary?
Negative feedback.
31
At what concentrations do estrogens exert negative feedback?
Both low and high concentrations.
32
At what concentrations do progestins exert negative feedback?
Only at high concentrations.
33
How do estrogens inhibit GnRH neurons in the hypothalamus?
Estrogens stimulate interneurons that inhibit GnRH neurons.
34
What neurotransmitter is involved in the inhibition of GnRH neurons in the arcuate nucleus?
Opiates.
35
What neurotransmitter is involved in the inhibition of GnRH neurons in the preoptic area?
GABA.
36
What effect do inhibins have on FSH secretion?
Inhibins inhibit FSH secretion by the gonadotrophs of the anterior pituitary.
37
What is the initial action of inhibins in FSH secretion?
Beyond the Ca2+-mobilization step.
38
Do inhibins affect mRNA levels of βLH?
No, inhibins have no effect on the mRNA levels of βLH.
39
What is the effect of activins on FSH release?
Activins promote marked increases in βFSH mRNA and FSH release.
40
What is the therapeutic use of pulsatile GnRH administration?
To treat clinical problems requiring increased gonadotropin secretion.
41
What condition requires pulsatile GnRH administration?
Kallmann syndrome.
42
What is endometriosis?
A condition caused by the abnormal presence of endometrial tissue outside the uterine cavity.
43
What is the effect of continuous GnRH administration in endometriosis?
Inhibits replenishment of the receptor for GnRH in the gonadotrophs, diminishing gonadotropin secretion.
44
What is the effect of continuous GnRH administration on leiomyomas?
Decreases estrogen levels and reduces proliferation of these estrogen-dependent lesions.
45
What is required for estrogen biosynthesis?
Two ovarian cells and two gonadotropins.
46
What cells synthesize estrogens during the follicular phase?
The follicle.
47
What cells synthesize estrogens during the luteal phase?
The corpus luteum.
48
What is the role of theca cells in estrogen production?
They take up cholesterol and produce adrenal androgens but lack aromatase.
49
What is the role of granulosa cells in estrogen production?
They have aromatase, which converts androstenedione to estradiol.
50
In the follicular phase, how do granulosa cells obtain cholesterol?
By de novo synthesis.
51
What is the major product of the follicle during the follicular phase?
Estradiol.
52
What is the major product of the corpus luteum during the luteal phase?
Progestins.
53
What does the two-cell, two-gonadotropin model involve?
LH stimulates the theca cell to convert cholesterol to androstenedione.
54
What happens to androstenedione in the follicular phase?
It diffuses to the granulosa cell, where it is converted to estradiol.
55
What occurs in the luteal phase regarding progesterone production?
Both theca-lutein and granulosa-lutein cells can produce progesterone.
56
What is necessary for the conversion of progesterone to 17α-hydroxyprogesterone?
17α-hydroxylase activity in the theca-lutein cell.
57
What is the first step in the two-cell, two-gonadotropin hypothesis for estrogen synthesis?
LH stimulates the theca cell via the adenylyl cyclase pathway to increase the synthesis of LDL receptors and side-chain-cleavage enzyme.
58
What occurs in step 2 of estrogen synthesis in the two-cell, two-gonadotropin hypothesis?
The theca cell increases its synthesis of androstenedione.
59
In step 3 of the estrogen synthesis process, what happens to androstenedione?
Androstenedione synthesized in the theca cells freely diffuses to the granulosa cells.
60
What is the role of FSH in the synthesis of estrogen?
FSH stimulates the granulosa cell to produce aromatase.
61
What does aromatase convert androstenedione into?
Aromatase converts androstenedione to estrone.
62
How can testosterone be formed from androstenedione?
17β-HSD can convert androstenedione to testosterone, which is then converted to estradiol by aromatase.
63
What is the effect of weak androgens at low concentrations in the follicle?
They are substrates for estrogen synthesis by granulosa cells and enhance aromatase activity.
64
What happens to weak androgens at high concentrations?
They are preferentially converted by 5α-reductase to more potent androgens like dihydrotestosterone (DHT).
65
True or False: Dihydrotestosterone (DHT) can be converted to estrogen.
False.
66
What effect do androgens have on aromatase activity?
5α-reduced androgens inhibit aromatase activity.
67
What occurs in the luteal phase regarding the corpus luteum?
The formation of the corpus luteum increases vascularity of the granulosa-lutein cells.
68
What is the net effect of increased vascularity in the luteal phase?
Facilitates delivery of LDL cholesterol to the granulosa-lutein cells and increases progesterone biosynthesis.
69
Why can't granulosa-lutein cells directly make 17α-hydroxyprogesterone or estradiol?
They lack the protein that has dual activity for 17α-hydroxylase and 17,20-desmolase.
70
What must happen for 17α-hydroxyprogesterone synthesis?
Progesterone must first move to the theca-lutein cell.
71
What is the role of aromatase in the granulosa-lutein cell?
It converts androstenedione to estradiol.
72
What is the primary function of estrogens?
Stimulation of cellular proliferation and growth of sex organs and other tissues related to reproduction.
73
Approximately what percentage of estradiol in the blood is bound to albumin?
About 60%.
74
What are the two main carrier proteins for estradiol?
* Albumin
* Sex-hormone binding globulin (SHBG)
75
What happens to the estrogen-estrogen receptor complex?
It interacts with steroid-response elements on chromatin to induce transcription of specific genes.
76
What does progesterone induce in reproductive tissue?
Glandular secretion and maturation of estrogen-stimulated tissue.
77
During which phase of the menstrual cycle does progesterone induce final maturation of the uterine endometrium?
The latter half of the menstrual cycle.
78
What are the three major phases of the endometrial cycle?
* Menstrual phase
* Proliferative phase
* Secretory phase
79
What occurs in the proliferative phase of the endometrial cycle?
Endometrium is restored through proliferation of basal stromal and epithelial cells.
80
How thick can the endometrium become during the late proliferative phase?
Thickening from about 0.5 mm to as much as 5 mm.
81
What growth factors are induced by estrogens during the endometrial cycle?
* Insulin-like growth factors (IGFs)
* Transforming growth factor (TGF)
* Epidermal growth factor (EGF)
82
What role do estrogen and progesterone play in the endometrium?
Estrogen induces progestin receptors in endometrial tissue; progesterone opposes estrogen's action on epithelial cells.
83
When do levels of progestin receptors peak in the menstrual cycle?
Levels peak at ovulation, when estrogen levels are highest.
84
What enzymes does progesterone stimulate to exert its anti-estrogen effects?
17β-HSD and sulfotransferase.
85
What is the effect of progesterone on epithelial cell proliferation?
It inhibits proliferation but promotes proliferation of the endometrial stroma.
86
What is predecidualization?
The process where stromal cells surrounding spiral arteries enlarge and develop eosinophilic cytoplasm.
87
What distinguishes the compact area of the endometrium?
Edema of the midzone of the endometrium.
88
Fill in the blank: The functional layer of the endometrium is composed of the superficial zona compacta and the _______.
mid-level zona spongiosa.
89
What happens to the endometrium during the late luteal phase of the menstrual cycle?
Levels of estrogens and progestins diminish, leading to demise of the upper two-thirds of the endometrium.
90
What is the average blood loss during menstruation?
About 30 ml.
91
True or False: Menstrual blood clots due to the presence of fibrolysins.
False.
92
What are the three regimens of contraceptive steroid administration?
* Monophasic
* Multiphasic
* Progestin-only.
93
What is the average age of menopause in American women?
51.5 years.
94
What happens to ovarian steroid levels during menopause?
Levels fall, while gonadotropin levels rise.
95
What is atresia in the context of ovarian follicles?
Degeneration of ovarian follicles that do not ovulate.
96
How many oocytes are estimated to be ovulated during a woman's reproductive life?
More than 400.
97
What biochemical changes occur in decidual cells under the influence of progesterone?
They form secretory products typical of decidual cells.
98
What is the significance of the zona basalis in the endometrium?
It is the layer left after birth or menstruation that gives rise to the proliferation at the start of the next cycle.
99
What is the effect of contraceptive steroids on gonadotropin releasing hormone?
They decrease its secretion at the level of the hypothalamus and gonadotrophs.
100
List some risks associated with oral contraceptives.
* Benign liver tumors
* Cholelithiasis
* Hypertension
* Heart attack
* Stroke
* Deep vein thrombosis
* Pulmonary embolus.
101
What happens to FSH levels as a woman approaches menopause?
FSH levels increase due to decreased ovarian production of estrogen.
102
What is the primary function of the secretory phase of the menstrual cycle?
To prepare for the arrival and implantation of the blastocyst.
103
What happens to ovarian production of estrogen during menopause?
Decreased ovarian production of estrogen
## Footnote
This reduction leads to decreased negative feedback to the anterior pituitary.
104
What is the consequence of decreased estrogen on FSH levels?
Increased levels of FSH
## Footnote
Increased FSH levels can be seen as early as 35 years of age.
105
How does estradiol production in older premenopausal women compare to younger women?
Diminished estradiol production and decreased luteal function
## Footnote
This occurs during natural cycles.
106
What contributes to the rise in FSH levels during the perimenopausal period?
Diminished inhibin production by the aging ovary
## Footnote
This contributes to the sharp rise in FSH levels.
107
List some physical changes associated with menopausal syndrome.
* Vasomotor instability
* Atrophy of the vaginal epithelium
* Hot flashes
* Changes in vaginal pH
* Night sweats
* Decrease in vaginal secretions
* Mood changes
* Decrease in circulation to vagina and uterus
* Short-term memory loss
* Pelvic relaxation
* Sleep disturbances
* Headaches
* Loss of vaginal tone
* Loss of libido
* Cardiovascular disease
* Osteoporosis
* Alzheimer’s disease
108
What is female sexual desire or libido modulated by?
Circulating sex steroids
## Footnote
Libido varies during the ovarian cycle and increases around ovulation.
109
What causes the increase in libido around ovulation?
Increased secretion of androgens
## Footnote
This occurs just before and during ovulation following the LH surge.
110
What are the four distinct phases of the female sex response?
* Excitement
* Plateau
* Orgasm
* Resolution
111
Which part of the nervous system primarily controls the excitement phase of female sexual response?
Parasympathetic fibers emanating from the sacral plexus
## Footnote
These fibers innervate erectile tissues.
112
What causes engorgement and erection of the clitoris?
Dilatation of blood vessels in the erectile tissues due to the release of acetylcholine
113
How is female orgasm coordinated?
Through a spinal cord reflex that results in rhythmic contractions of the perineal muscles
114
What are the afferent pathways for the spinal cord reflex during female orgasm?
Follow the pudendal nerves
## Footnote
These nerves are the primary innervation to the perineum and the female external genitalia.
115
True or False: The female sex response facilitates sperm transport through the female reproductive tract.
True
116
What system controls the female sex response?
Autonomous nervous system
