Lecture 11: The Follicular Phase
General Regulation of Hormonal Pattern in Female (figure 1a,b)
- Hypothalamus secrets GnRH
- Anterior Pituitary secrets LH and FSH
- stimulates follicle and/or CL growth and maintenance
- Follicle produces Estradiol and Inhibin
- estradiol has positive and negative feedback
- inhibin inhibits FSH release
- CL produces progesterone
- progesterone has negative feedback
Preovulatory Hormonal Regulation
- progesterone decreases due to effects of PGF
- in response, FSH and LH increase
- removal of negative feedback by progesterone
- preovulatory follicle produces inhibin and estradiol
- inhibin keeps FSH under check although FSH continues to increase because of estradiol positive feedback effects (see below)
- estradiol has positive feedback effects
- in absence of progesterone, estradiol stimulates the surge center in the hypothalamus
- GnRH and then LH increase
- cycle continues until LH surge occurs to trigger ovulation
- primordial, primary, secondary and tertiary follicles (figure 2)
- atresia can occur at any step (figure 3)
Follicular Growth (figure 4 , figure 5)
- gonadotropin independent phase
- FSH dependent
- recruitment = emergence
- selection
- dominance
- presence of 2 and 3 wave cycles (figure 6)
- FSH triggers the recruitment of follicles into and emergence of a follicular wave (recruitment = emergence)
- species variation
Production of estradiol by antral follicle (figure 15)
- theca interna has LH receptor and produces androgen (testosterone)
- granulosa cell has FSH receptor which when activated causes cell to take testosterone from theca and convert it to estradiol
- FSH causes increased activity of aromatase enzyme (converts testosterone to estradiol)
- after recruitment and selection, dominant follicle has LH receptors on granulosa and granulosa can then respond to principally LH to drive estradiol production.
- layers oocyte must cross to ovulate (figure 9)
- events in follicle which if blocked will prevent ovulation
- protein synthesis
- steroid synthesis
- prostaglandin synthesis (both PGF and PGE)
- plasminogen activator synthesis
Ovulation (in response to LH; figure 10)
- cumulus cells produce hyaluronic acid and proteins to cause cumulus expansion
- the cumulus and oocyte separate from the granulosa cells
- increased blood flow to follicle
- local response mediated by increases in PGE2 and histamine
- follicle also produces angiogenic factors
- increased vascular permeability produces edema in tissue surrounding follicle and increased plasminogen
- follicular pressure increases
- triggers changes in protein synthesis and cellular differentiation within follicle
- steroid biosynthesis shifts to production of progesterone
- triggers production of inactive collagenase from theca interna
- PGE2 and PGF2 are produced
- triggers production of plasminogen activator from granulosa
- steroid biosynthesis shifts to production of progesterone
- plasminogen is converted to plasmin by plasminogen activator
- plasmin converts inactive collagenase to the active form which then weakens the collagen of the tunica albuginea and thecal layer
- granulosa cells also increase production of follicular fluid
- stigma begins to push out and weaken
- follicle ruptures
- PGF stimulates smooth muscle to contract and force the ruptured follicle to empty
Types of Ovulators
- spontaneous
- ovulate with regular frequency and do not require copulation
- induced
- requires vaginal and/or cervical stimulation for ovulation
- even spontaneous ovulators retain some neural control over ovulation
- heifers with clitoral message can shift time of LH surge
- rape leads to more higher pregnancy that expected
- mitotic divisions of primordial germ cells (figure 11)
- nuclear arrest at dictyotene (figure 11 , figure 12)
- cytoplasmic growth
- nuclear maturation
- cytoplasmic maturation
- resumption of meiosis (figure 13 ; figure 14)
Old Coverage of Follicular wave dynamics that might prove helpful if confused or for review (figure 8)
- anovulatory wave
- growing phase
- Initial growth (recruitment) is under influence of FSH
- Inhibin secreted to decrease FSH and development of subordinate follicles (estrogen also; selection)
- Dominant follicle becomes less dependent on FSH for growth
- FSH induces LH receptors in granulosa
- Dominant follicle produces estradiol and androgens in response to LH and FSH
- Androgens, lack of FSH may cause subordinate follicles to become atretic (dominance)
- static phase
- Inhibin production stops
- FSH increase stimulates follicular wave
- Estradiol from dominant follicle decreases and androgens increase, this may initiate atresia of dominant follicle
- regressing phase
- Dominant follicle becomes atretic and looses steroidogenic capability
- growing phase
- ovulatory wave
- growing phase
- same events as in growing phase of anovulatory wave
- LH continues to increase in response to estradiol positive feedback in the absence of progesterone
- Dominant follicle increases in size and estrogen production
- LH surge occurs to trigger ovulation of the dominant follicle
- growing phase
- Figure 1a, b. General hormonal control in the female.
- Figure 12. Meiotic Arrest in the Oocyte
- Figure 13. Effect of the LH Surge on Meiotic Arrest
- Figure 14. Ovulation, Fertilization and Resumption of Meiosis
- Figure 15. 2-Cell 2-Gonadotropin Model for Steroid Production by the Follicle
