Female endocrinology 2

Question 1

What occurs in the luteal phase…? How can these events be categorised?

Answer 1

Follicular cells -> luteal cells
Dev. of CL & prod. of P4 (lutenisation)
Destruction of CL & resumption of follicular phase (luteolysis)
Categorised as events following ovulation

Question 2

First part of the luteal phase? (Directly after ovulation)

Answer 2

metestrus

Question 3

What occurs during metestrus…?

Answer 3

formation of CL (gradual increase in P4)

Question 4

What phase follows metestrus?

Answer 4

diestrus

Question 5

What occurs during diestrus…?

Answer 5

P4 dominating hormone produced by functioning CL

Question 6

Thecal cells have receptors for… and produce…?

Answer 6

LH and produce testosterone

Question 7

Granulosa cells have receptors for… and produce…?

Answer 7

FSH and produce oestrogen

Question 8

In the pre-ovulatory follicle (oestrus), what happens to the basement membrane?

Answer 8

Starts to deteriorate allowing granulosa & thecal cells to contact each other (because of increased pressure build up within follicle - antrum)

Question 9

What happens to corpus haemorrhagicum (CH) during ovulation…?

Answer 9

Follicular walls collapse due to deteriorated basement membrane
Local haemorrhage
Ruptured blood vessels
Gland is formed consisting of thecal & Granulosa cells & connective tissue -> (CL)

Question 10

What does the corpus luteum (CL) consist of…?

Answer 10

Mix of large luteal cells (LLC - granulosa cells) & small luteal cells (SLC - thecal cells)

Question 11

When does the CL begin to increase in size?

Answer 11

Day 3-5

Question 12

What determines the amount of progesterone produced by the CL?

Answer 12

The maximum size of the CL

ie. the bigger the CL, the more P4 produced by it.

Question 13

Luteal formation in the cow…? What happens to CL, LLCs, SLC…?

Answer 13

CL begins to increase in size until halfway thru Luteal phase
Hypertrophy of LLCs, Hyperplasia of SLCs, peak P4 production (diestrus), orange CL colour reflects high beta carotene

Question 14

Functional capability of CL & progesterone production depends on…?

Answer 14

Number of functioning luteal cells

Degree of vascularisation within CL (hormone delivery)

Question 15

Insufficient luteal function results in…?

Answer 15

Reduced ability of uterus to support pregnancy

Reproductive failure

Question 16

How would you treat insufficient luteal function results in…?

Answer 16

Supplement with progesterone

Question 17

Describe progesterone synthesis…?

Answer 17

1. LDL-CHOL bind to membrane receptors -> 2. LH binds to LH receptor on membrane -> 3. activates protein kinase -> 4. CHOL moves into mitochondria -> 5. CHOL -> pregnenolone -> into cytoplasm -> preg -> progesterone -> out of cell to target tissue

Question 18

Physiological effects of progesterone…?

Answer 18

Hypothalamus
- -ve feedback on GnRH
- supression of LH & FSH & oestrogen -> behaviour
Uterus
- glandular edometrium -> maximal secretion (in preparation for embryo…fetus…birth)
- Muscular myometrium (muscle layer within uterus) -> inhibition of motility (stop uterine contractions/still/calm)
Mammary gland
- alveolar development (ready for milk production at end of gestation)

Question 19

Describe the events in luteolysis…

Answer 19

• disintegration of CL
• occurs near end of luteal phase (1-3 days)
• significant reduction of P4 production
• regulated by oxytocin, prog. & prostaglandin (PGF2alpha)

Question 20

In sheep studies, what occurred to CL lifespan when uterus was 1. left intact, 2. underwent uterectomy, 3. partial uterectomy contralateral to CL, 4. partial uterectomy ipsilateral to CL?

Answer 20

1. 15 - 17 d
2. 148 d
3. 15 - 17 d
4. 35 d

Question 21

THMessage from sheep uterectomy studies…?

Answer 21

Local circulation of PGE 2alpha important for proper CL destruction, if no PGE 2alpha released from uterus -> CL was NOT destructed

Question 22

How does PGE 2alpha get to the ovary?

Answer 22

via a vascular counter current exchange system

PGF 2a produced by uterine endometrium -> uterine vein & lymph -> ovarian artery via passive diffusion -> ovary

Question 23

What happens to PGF 2a in normal circulation?

Answer 23

denatured thru pulmonary system

Question 24

Why is counter current mechanism important in the cow & sow?

Answer 24

As it allows adequate levels of PGF 2a to exert lytic effects directly on functional CL

Question 25

When is PGF 2a effective on the CL in the cow & sow?

Answer 25

cow (5-6 days after ovulation) | sow (12-14 days after ovulation)

Question 26

Why would exogenous PG be administered?

Answer 26

To artificially lyse CL to syncronise oestrus & induce parturition (eg. sheep to give birth to lamb)

Question 27

What is oxytocin's role in luteolysis...? Where is it produced & stored? How & when is it released?

Answer 27

Produced by luteal cells, stored in secretory granules until threshold is reached. Released in pulsatile manner towards end of luteal phase -> causes release of PGF 2a from endometrial cells

Question 28

Where & when do oxytocin receptors form?

Answer 28

Endometrial cells, 10-12 days after ovulation

Question 29

What blocks formation of oxytocin receptors?

Answer 29

progesterone (P4)

Question 30

Requirements for luteolysis in the cow...?

Answer 30

- presence of oxytocin receptors in endometrium - presence of critical secretion of oxytocin via LLCs - PGF synthesised by endometrium, released in pulsatile secretion & critical number of pulses required for luteolysis - presence of PGF 2a receptors on CL

Question 31

Events that occur after luteolysis...?

Answer 31

- Reduction of P4 - CL forms Corpus Albicans - Macrophages & lymphocytes phagocytise damaged luteal cells - New follicular dev. & recruitment of antral follicles

Question 32

Main difference between luteolysis in humans/primates compared to other domestic breeds...?

Answer 32

- controlled by hypothalamus & ovary NOT uterus (not required) - PGF 2a produced by ovary in response to oxytocin release from posterior pituitary - reduction in P4 -> PGF 2a synthesis from endometrium of ovary -> endometrial vasoconstriction, necrosis & sloughing -> MENSES (discharge of blood & cellular debris)

Question 33

What effects does exogenous progesterone have...?

Answer 33

- mimics the luteal phase (lengthen or reduce) - provides -ve feedback on hypothalamus -> supress GnRH release - suppress oestrus behaviour (horses) - allows synchronisation of individuals -> in AI or ET programs - contraceptive in humans -> block ovulation & minimise pregnancy

Question 34

What is CIDR?

Answer 34

controlled internal drug release

Question 35

How does synchronisation in cows work?

Answer 35

``` via CIDR (P4 as drug) inserted into vagina & releases P4 diffuses across vaginal mucosa -> blood stream -> suppresses GnRH, follicular dev. & ovulation eg. administer CIDR for 7 days to all cows then remove => all cows synchronised so that when [P4 plasma] levels fall -> PGF 2a can be injected -> luteolysis in all cows -> proestrus phase -> oestrus phase ```

Question 36

How can synchronisation be achieved without CIDR?

Answer 36

By single injections with PGF2a between day 7 & 18 -> luteolysis -> oestrus 2-3 days later (Days 1-7 the CL is refractory to PGF2a & will NOT respond)

Question 37

When would a double injection (PGF2a) protocol be used?

Answer 37

When a small % of cows aren't responsive to a single PGF2a dose (14 days apart) -> all cows should cycle together

Question 38

What mechanism does PGF2a use to reach ovary in domestic spp.?

Answer 38

utero-ovarian vascular countercurrent diffusion system

Question 39

Which hormone can be used to cause letenisation?

Answer 39

LH or hCG (has LH-like activity)