Topic 91 - Hormonal changes during the estrus cycle

Question 1

Words to inculde

Answer 1

• Ovulation
  
  • E2 level high
  • GnRH → LH peak → ovulation
• LH peak
  
  • Induces ovulation
  • Luteinization process
• Corpus haemorragicum, luteinization
  
  • E2 and FSH level ↓
  • Luteninization due to previous LH peak
  • PRL level ↑
• Early phase of corpus luteum
  
  • P4 level ↑
• Flourishing corpus luteum
  
  • P$ level ↑

Luteal phase

• Growing phase of corpus luteum
• P4 level ↑
  
  • Due to ovulation and luteinization (ø ca)
• PRL level ↑
• Flourishing corpus luteum
  
  • Plasma E2 low
    
    • Due to negative effect of high P4 on CNS

Luteolysis (end of luteal phase)

• PGF_2α production in uterus → lysis of corpus luteum → plasma P4 ↓
• PGF_2α ​
  
  • Endometrium → ovary
    
    • Ru: v. endometrial → a. ovarica
    • Eq: systemic circulation

Follicular phase

• FSH level ↑
  
  • Induces next ovarian cycle
• Inhibin produced
• High level of E2 and FSH → GnRH peak

Hypothalamus - pituitary - gonad axis

• GnRH secretion
  
  • Tonic releasing center
    
    • Ventromedial hypothalamic nucleus (location)
    • Base levels of GnRH
    • Normal E2 and P4 plasma concentration
    • Negative feedback
  • Pulsatile releasing surge center
    
    • Preoptic area (location)
    • Positive feedback

Estrogen

• The relevance of preovulatory estrogen peak
  
  • Pre-ovulatory E2 levels ↑ → GnRH peak & LH peak → ovulation
  • Negative-positive feedback change of the hypothalamic GnRH cells
• Role of elevated E2 levels
  
  • Positive / negative feedback
  • Diestrus, metestrus: low E2 level
  • Proestrus: elevated E2 level
    
    • Negative feedback → positive feedback → GnRH peak / surge
    • Gonadotropic cells ↑
      
      • Adenohypophysis
      • GnRH ↑ → LH peak

Luteinizing hormone (LH)

• Peptide hormone
• Secretion regulation:
  
  • GnRH
  • Sexual steroids
    
    • Positive: E2
    • Negative: P4
• Role:
  
  • Surge center → GnRH ↑ → LH peak → ovulation, luteinization
  • Induced ovulators: Copulation → neuroendocrine reflex arch → LH peak → ovulation, luteinization
• Supports theca cells
  
  • Provides androgens & hormonal precursors for estradiol production
  • FSH intiates follicular growth affecting granulosa cells
  • E2 level ↑ → LH receptors expressed on maturing follicle → estradiol production ↑
• LH peak / surge
  
  • Trigger ovulation
  • Residual follicle → corpus luteum
    
    • P4 production to prepare endometrium

Refractory period of corpus luteum

• PGF_2α
  
  • No effect on corpus luteum for 2-5 days after ovulation

Regulation of seasonality

• ​Length of diurnal periods (stimulator)
  
  • “Rushing into cycle”
• Melatonin concentrations
• Fall:
  
  • Length of dark period > 9.5 hours
  • Sheep: cycle starts
  • Eq: cycle inhibited
• Spring:
  
  • Length of dark period < 9.5 hours
  • Sheep: cycle inhibited
  • Eq: cycle starts
• Sheep: estrus cycle in short-day periods
• Eq: estrus cycle in long-day periods

Question 2

Topics to include in the essay

Answer 2

1. Review of hormonal events
2. Secretion of Gnrh
3. Hypothalamus-hypohphysis-gonad axis
4. Estrogen
   
   • The relevance of preovulatory E2 peak
   • Role of elevated E2 levels (+ /- feedback)
5. Luteinizing hormone (LH)
6. Refractory period of corpus luteum
7. Regulation of seasonality
   
   • Horse and sheep

Question 3

Figure: a review of hormonal events in cow

Answer 3

• Chagens of plasma hormone leves during estrus cycle
• Ovulation (18-0)​
  
  • High level of E2
  • GnRH then LH peak → ovulation
    
    • ​LH peak incues the ovulation and luteinization process
  • High level of H2
• Corpus haemorragicum, luteinization (0-5)
  
  • Dropping level of E2 and FSH
  • Due to previous LH-peak, luteinization is in progress
  • PRL levels ↑
• Early phase of corpus luteum (5)
  
  • ​P4 levels ↑
  • A new generation of follicular cohort starts developing, but increasing P4 levels stops the process
• Flourishirng corpus luteum (10-15)
  
  • ​High level of P4
  • Other hormones are on a baseline concentration
  • A new generation of follicles starts beveloping, but these follicles soon udergo the stresia
• Luteolysis, early follicular development (15-18)
  
  • ​Non-pregnant animals
  • PGF_2α is produced by the uterus → lysis of corpus luteum
  • P4 level ↓ → FSH level ↑
• Follicular development and selection (17-21)
  
  • Increasing FSH levels stimulate the follicular development
  • Inhibis is produced by the fastest developing follicle (dominant follicle)
    
    • Inhibin blocks the other developing follicles
    • Some species: Inhibin cause a sharp drop in plasma FSH levels (negative feedback)
  • Due to constant high level of E2 and FSH, GnRH peak (followed by LH peak) develops and consequently next ovulation happens

Question 4

Secretion of GnRH

Answer 4

• GnRH: Gonadotropin Releasing Hormone
• GnRH frequency is influenced by:
  
  • Estrous phase (hormones)
  • Season (melatonin)
  • Energy balance
• Integration:
  
  • ​Kisspeptin-containing neurons

Question 5

Hypothalamus-hypophysis-gonad axis

Answer 5

• Feedback mechanism
• Two aspects of GnRH secretion:
  • Tonic releasing center
    
    • Location: ventromedial hypothalamic nuclei​
    • Ensures base levels of GnRH secretion necessary for functioning of the gonads
    • Normal E2 and P4 plasam concentration
    • Negative feedback loop
  • Pulsatile releasing surge center
    
    • Location: preoptic area
    • ​Produces a peak above the base level in every cycle
    • This center is stimulated by the high level of E2, a positive feedback loop
    • P4 in high concentration inhibits this center
    • The cyclic center affects functioning of the toic center

Question 6

Estrogen

Answer 6

• Estrogen = E2

​The relevance of preovulatory estrogen peak

• Rising pre-ovulatory estrogen levels directly prepare the GnRH peak and LH peak and therefore the ovulation
  
  • ​Pre-ovulatory estrogen level → GnRH peak and LH peak → ovulation
  • Negative-positive feedback change of the hypothalamic GnRH cells

Role of elevated E2 levels (+/- feedback)

• E2 levels shows strong fluctation:
  
  • Diestrus, metestrus: low level
    
    • Inhibits the central GnRH secretion that keeps the noral baseling level of GnRH and LH in the circulation
  • Proestrus: elevates rapidly
    
    • Constant high level of E2 changes the feedback state of the GnRH cell from negative feedback to positive feedback → GnRH peak
    • Sensitivity of gonadotropic cells (FSH, LH) in the adenohypophysis icreases, and the elevated GnRH induces LH peak
    • LH peak → ovulation of fully matured follicle

Question 7

Luteinizing hormone (LH)

Answer 7

• Peptide hormone
• Secretion regulated by:
  
  • GnRH
  • Sexual steroids
    
    • ​Positive: E2
    • Negative: P4
• Role:
  
  • Surge center → GnRH ↑ → LH peak → ovulation, luteinization
  • ​Induced ovulators: Copulation → neuroendocrine reflex arch → LH peak → ovulation, luteinization
• LH supports theca cells in the ovaries that provides androgens and hormonal precursors for estradiol production
  
  • FSH initiates follicular growth affecting granulosa cells → E2 increase → LH receptors expressed on the maturing follicle → estradiol production ↑
• GnRH in the hypothalamus stimulates the release of LH from the anterior pituitary → LH peak
• LH surge / LH peak triggers ovulation resulting in:
  
  • Releasing egg from follicle
  • Initiating the conversion of the residual follicle → corpus luteum whic produces P4 for preparation of endometrium for possible implantation

Question 8

Refractory period of corpus luteum

Answer 8

• PGF_2α has no effect on the corpus luteum for 2-5 days after ovulation

Refractory period of corpus luteum, interspecies

• Ru: 4 days
• Sus: 5 days
• Eq: 13 days

Question 9

Regulation of seasonality

Answer 9

• The most important stimulator in seasonality is the length of diurnal periods, that determines the “rushing into cycle” process
• Major role: Melatonin concentrations
• During fall:
  
  • Length of dark period ↑, becomes more than 9.5 hours
  • The “rushing into cycle” starts for those which are sensitive for short day
    
    • Sheep: activated cycle
    • Eq: inhibited cycle
• During spring:
  
  • Length of the dark periods ↓, becomes less than 9.5 hours
  • Cycle starts for those which are sensitive for long day light
    
    • Sheep: inhibited cycle
    • Eq: activated cycle