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Functional luteolysis
-PGF2a producing in the CL and the uterus
-PGF2a travels to the ovary
-PGF2a binds to receptor on large luteal cell
-Increase oxytocin
-binding to large luteal cell causes calcium channels to open
-PGF2a signaling reuslts in LDL receptor reduction
All of this ultimately leads to a decrease in progesterone
What does functional luteolysis result in?
a decrease in progesterone
Structural luteolysis
-calcium channels open causing polarity change within luteal cells which leads to apoptosis of luteal cells
a. small luteal cells and endothelial cells die first
b. large luteal cells die second
c. immune cells digest and remove cells
d. there will only be CT left (corpus albicans)
What happens if the female does not become pregnant?
Luteolysis
What is luteolysis?
disintegration of CL
When does luteolysis occur?
1-3 day period at end of diestrus
When does lysis of the CL have to occur?
before entering the follicular phase
What is PGF2a?
hormone sourced from the CL on the ovary and uterus
What is oxytocin?
hormone sourced from the hypothalamus and CL
Where does oxytocin come from?
First from the hypothalamus and after luteolysis it comes from CL
What is progesterone?
hormone sourced from the CL on the ovary and placenta
T/F: the uterus is required for successful luteolysis in many species
true
If the female loser her uterus completely how long will CL be maintained?
148 days
What hormone released from the uterine horn plays a major role in luteolysis?
PGF2a
T/F: PGF2a is local and stays in the reproductive tract
true
Where is PGF2a produced?
uterine endometrium
How does PGF2a enter the CL?
without dilution
Where is PG metabolized at a high rate?
the lungs
What % of PG is metabolized in the lungs in cows/ewe?
90%
What % of PG is metabolized in the lungs in sows?
40%
How does PGF2a signal luteal cells?
-PGF2a binds to receptors on luteal cells (specifically large)
-PGF2a receptor complex opens calcium channels
-high intracellular calcium leads to apoptosis
-PGF2a complex also activates protein kinase c that inhibits progesterone synthesis
Luteal regression in ruminants
-oxytocin released from posterior pituitary stimulate pulses of PGF2a from uterus
-PGF2a from uterus stimulates OT from CL which stimulates uterine PGF2a
-If there is no conceptus present, then there will be an increase in oxytocin receptors
-oxytocin is produced in the brain and binds to receptors in the endometrium
-binding to receptors in endometrium triggers PGF2a production
-PGF2a will be kept at tonic release and oxytocin receptors will be limited
How many spikes/pulses of PGF2a kill a CL?
5
What be present for a hormone to cause a response?
receptor
What phase of estrous does a CL produce progesterone?
diestrus
How does the CL produce progesterone?
-Cholesterol is imported to the luteal cell by LDL
-LH binds to LH receptors on the membrane of luteal cells
-LH binding causes protein kinase to be released
-LH receptor complex activates intracellular cascade that stimulates adenylate cyclase which stimulates production of 2nd messenger cAMP
-mitochondria enzymes convert cholesterol to pregnenolone
-pregnenolone is converted to progesterone in the smooth ER
What is tonic release?
slow drip, comes in episodes
What is surge release?
high frequency or amplitude
What is negative feedback?
reduce the change
What is positive feedback?
increase the change
What does the hypothalamus produce?
GnRH
Where does GnRH have an effect?
anterior pituitary
What does the anterior pituitary produce?
LH and FSH
Where does LH and FSH have an effect?
ovarian structures (follicle, CL)
What type of feedback loop are GnRH, LH, and FSH?
positive
When the female is pregnant, what type of feedback loop is initiated and why?
negative b/c when a female is pregnant some hormones need to be in smaller quantity. The CL will cause the follicle not to ovulate and produce progesterone
How do hormones produced in the brain play a role in the 2 cell theory?
LH and FSH are released from the anterior pituitary and stimulate the release of different enzymes to cause a reaction
Where is estrogen produced?
follicle
What does estrogen cause?
estrus (standing heat)
Where is progesterone produced?
corpus luteum
What is the function of progesterone?
maintain pregnancy
Where is testosterone produced?
theca cells
How do hormones play a role in the development of the CL?
-progesterone reduces the release of LH
-progesterone stimulates the production of collagenase to bread down the basement membrane ultimately leading to the follicle "imploding" and forming the CH. (CH develops into CL)
-progesterone decreases the number of GnRH receptors on ant pit causing a reduction in LH and FSH secretions
How hormones play a role in the regression of the corpus luteum?
-PGF2a is produced in the uterus when oxytocin binds to itns receptor. PGF2a tavels locally and without dilution to the CL where it causes luteolysis
-When PGF2a binds to its receptors on the large luteal cells it reults in decrease in LDL and LH receptors, increases oxytocin, and causes the complex to open calcium channels (leads to apoptosis) and to activate protein kinase (inhibits progesterone production)
What takes away the function of the CL?
functional luteolysis
What destroys the structure of the CL and leaves a corpus albicans?
structural luteolysis
How do hormones play a role in behavioral changes during estrus?
When estrogen is the dominant hormone, behavioral and physiological changes take place.
Ex: increased locomotion, vocalization, nervousness, mounting, receptive to male
How do estrogen, LH and FSH work together?
-Increase in estrogen stimulates GnRH secretions
-The increases GnRH causes an effect on ant pit leading to larger amounts of FSH and LH being released
What does an increase in estrogen concentrations do?
causes a surge of GnRH
How do progesterone, LH and FSH work together?
-When there are large amounts of progesterone, GnRH concentrations are low
-This low GnRH leads to reduced levels of FSH and LH
-follicular growth is decreased and the development of CL occurs
What portion of the estrous cycle does the follicular phase comprise of?
20%
What are the 2 stages of the follicular phase?
proestrus and estrus
Describe the proestrus stage
-Lasts 2-5 days and begins when progesterone declines due to luteolysis
-transition from progesterone dominance to estrogen dominance
-antral follicles mature for ovulation
Describe the estrus stage
-dominant hormone is estrogen
-behavioral changes occur
-standing heat
-antral follicle ovulates
What causes the shift from the follicular phase to the luteal phase?
-shift from estrogen dominance to progesterone dominance
-shift from follicle being dominant structure to the CL
What are the 2 stages of the luteal phase?
metestrus and diestrus
Describe the metestrus stage
-period between ovulation and functional CL
-estrogen and progesterone concentrations are low
-remaining follicular cells undergo remodeling (luteinization)
-progesterone secretion increases later in stage (2-5 days after ovulation)
What is luteunization?
follicle -> CH -> CL
Describe the diestrus stage
-10-14 days
-longest stage of estrous
-CL fully functional
-progesterone dominant hormone
-uterus prepares for early embryonic development
-diestrus ends when CL is destroyed
What are the 2 different ways a female does not display estrus?
-apparent anestrus
-true anestrus
Describe gestational anestrus
-lack of cyclicity (pregnant)
-elevated progesterone
What is a photoperiod?
period of time during the day when there is daylight
What does an increase in kiss - 10 hormone cause?
An decrease in GnRH
Short day breeders
Decrease in gonadotropins
How long is the follicular phase of the menstrual cycle?
50%
When does ovulation occur during the estrous cycle?
Beginning and end of the cycle
How long is the fertile period in the estrous cycle?
24 hours or less
What causes luteolysis in the estrous cycle?
Uterine PGF2a
Is there an increase or decrease in progesterone after luteolysis?
decrease
T/F: progesterone causes a positive feedback on the hypothalamus?
false
What is the function of progesterone in regards to the utereus?
Causes endometrial glands to coil and branch, stimulates "uterine milk" secretions
When does myometrial contractions and enzymatic activity shrink the uterus back to normal size in cows?
occurs 30-50 days after
Why is important for the vagina to have numerous layers of protection?
Is the copulatory structure (meaning that it is susceptible to tearing so it needs numerous layers of protection to prevent this from happening)
What are the major events of the follicular phase?
-luteolysis
-reduction in P4
-GnRH surge
-FSH and LH surge
-follicular development
-estrogen production
-preovulatory LH surge
T/F: follicles can still frow during the luteal phase, but cannot reach dominant or ovulatory status
True
What type of receptors do antral follicles contian?
FSH and LH
What are the 5 events of folliculogenesis?
-initiation and progression of preantral follicles
-recruitment of small antral follicles
-selection of growing cohort of recruited antral follicles
-dominance of 1 or more follicles
-follicular atresia occurring throughout
At what stage of the estrous cycle does recruitment of small antral follicles occur?
start of proestrus
At what stage of the estrous cycle does the selection of the growing cohort of recruited antral follicles occur?
Transition into proestrus and later in proestrus
At what stage of the estrous cycle does dominant 1 or more follciel occur?
during estrus
Is preantral growth gonadotropin independent or gonadotropin dependent?
gonadotropin independent
What causes the antral follicles to develop?
increased levels of FSH
What happens when FSH is increased?
-FSH causes antral follicles to grow
-as follicles grow they release larger amounts of estrogen
-larger amounts of estrogen stimulates GnRH secretion
-GnRH causes more gonadotropins
This is a positive feedback loop
Is recruitment FSH or LH dependent?
FSH dependent
What is the function of gap junctions?
communication between granulosa cells and oocyte
What does the LH surge do?
Stimulates the cumulus oorphus cells to produce hyaluronic acid which causes expansion of the COC, this increases surface area
What are histamines?
specific type of WBC that function to increase blood flow
stimulated by the LH surge reaching the follicle
What are angiogenic factors?
factors that produce new blood vessels from the preexisting blood vessels
What is the function of collagenase?
break down collagen or tissue fibers, ultimately breaking down the tunica albuginea
What is the function of proteases?
digest proteins. allows for a way the oocyte can leave the follicle to ovulate
What does inhibin do and what produces inhibin?
inhibits the amount of FSH being produced, is produced by the dominant follicle
During the dominance stage, what does the negative feedback loop cause?
Inhibin causes a negative feedback loop on ant pit which decreases FSH and increase LH levels
Right before ovulation, what happens to the receptors on the follicles and what hormone is produced?
-Granulosa cells will have LH and FSH receptors
-Shift from estrogen to progesterone production
-critical for ovulation to occur
Why is LH surge so important?
without LH surge, ovulation will not occur
The negative feedback on the hypothalamus brought on progesterone causes what?
follicular development to be reduced
What type of receptors do antral follicles have?
LH and FSH
Describe how dominant follicles develop in cattle, sheep, and horses
sequential waves during both the follicular and luteal phases of the estrous cycle
Describe how dominant follicles develop in swine, primates, and rodents
only develop during the follicular phase of the cycle
When does follicular atresia occur?
continuously throughout all stages of follicular development
2 cell theory
- LH and FSH are released from the brain (anterior pituitary) and travel through the blood to the ovarian follicle
- Aromatase: the enzyme that converts testosterone to estradiol (travels to the brain's surge center which causes a release of GnRH and then causes a surge of LH)
- The pre-ovulatory LH surge initiates a cascade of events necessary for ovulation - C-amp serves as a second messenger that stimulates the cells to turn on the enzymes to produce the steroid hormones
- During selection, the dominant follicle will receive the surge of LH (a granulosa cell that has the LH receptor, right before ovulation, granulosa cells have both the LH and FSH receptors)
What is luteolysis?
The process whereby luteal tissue (CL) undergoes regression and cell death