Reproductive Cyclicity - The Follicular Phase Pt.1

What are the four major events of the follicular phase?

1. Elevated gonadotropin secretion from anterior pituitary

2. Follicular growth and preparation for ovulation

3. Sexual receptivity (estrus)

4. Ovulation

What is the major hormone associated with the follicular phase?

• Estradiol

Describe what luteolysis is and what it initiates

• Luteolysis - the regression/destruction of the corpus luteum (CL)

  • CL regression leads to decreased P4

  • Initiates the follicular phase

• Negative feedback by P4 is removed

  • GnRH pulse patterns and frequency to increase

  • FSH & LH increase with greater GnRH secretion

  • Follicular development and increased E2

All of this is preceded by, and dependent on, low P4

Describe the roll of the HPG in the follicular phase

• Increase in GnRH from hypothalamus —→ Increases FSH & LH from anterior pituitary ——→ Increases follicular growth ———→ Increases E2 from follicles —→ Increase E2 and inhibin from follicles

Describe the role of GnRH in the follicular phase. Include the difference between the tonic and surge centers

Elevated GnRH is essential for initiating the follicular phase

• Tonic center produces basal levels of GnRH

  • Controls FSH and LH production, follicular growth

  • Small, pulsatile episodes continuously throughout life

  • Influenced negatively by P4

• Surge center produces surge of GnRH

  • Causes LH surge, ovulation

  • Controlled by combination of high E2, low P4

Review and draw the Follicular phase graph (incude Diestrus, proestrus, estrus, metestrus)

What are the three steps (phases of follicular maturation

Primary —→ Secondary ——→ Tertiary (Antral)

Describe the Tertiary (antral) follicle

• Contains a fluid-filled cavity (antrum) containing follicular fluid

• Consist of 3 distinct layers

  • Theca externa 0support follicle, loose connective tissue

  • Theca interna - produce androgens under control of LH

  • Granulosa cell layer

    • Excress FSH receptors

    • Produce E2,inhibin, and folliclar fluid

Define follicular dynamics

• Follicular dynamics - process of follicular growth and degeneration

  • Occurs continuously throughout the estrous cycle

  • Controlled by LH & FSH

What are the phases of antral follicle dynamics

• Recruitment - high FSH, low LH, low inhibin, low estraiol

• Selection - low FSH, moderate LH, low inhibin

• Dominance - low FSH, high LH, high inhibin

• Atresia - irreversible degeneration of follicles

Describe Recruitment and the hormone profile

A cohort of small antral follicles begins to grow and make estrdiol

Hormone profile:

• High FSH

• Low LH pulse frequency

• Low inhibin

• Low estradiol

Most recruited follicles will undergo atresia

Describe selection and the hormone profile

Follicles that do NOT undergo atresia are “selected”

• Selected follicles may become dominant of under atresia

Hormone profile

• Low FSH

• Moderte LH

• Low inhibin

As selected follicles proceed toward dominance, they produce increasing amounts of E2 and inhibin

• Inhibin= Decrease FSH from anterior pituitary

Describe dominance and the hormone profile. Also differentiate between a monotocous species and polyocous species

These are preovulatory follicles that inhibit the effect on antral follicles from recruited and selected cohorts

Hormone profile:

• Low FSH

• High LH pulse frequency

• High inhibin

Monotocous species (cow, mare, human): a single follicle is selected and develops dominance

Polytocous species (pig, dog,cat): a group of follicles is selected

Describe Atresia

>90% of ovarian follicles undergo atresia… far more follicles become atretic than those that obtain dominance

Recruitment, selection, and dominance are relatively short-term processes when compared to preantral stages

Describe how the different hormones are controlled and what they are used for

FSH & LH are controlled differently

• Inhibin, E2 = Decreased FSH

• GnRH pulse frequency = Increased LH

Primary role of LH:

• Promote final growth and maturation of dominant follicles

• Stimulate ovulation

Preparation of follicle for ovulation:

• Preovulatory follicles are recruited and selected during proestrus and evetually become dominant furing estrus

Describe the roles of FSH & LH in follicular dynamics

• Recruitment and Selection = follicles are FSH-dependent

• Selection, dominance, and preovulatory = follicles are LH dependent

Follicles with more LH receptors will become preovulatory follicles

Describe the 2-cell, 2-gonadotropin model for estradiol synthesis

Theca interna cells contain receptors for LH

• LH binds, initiaiting a cascade of intracellular events (GPCR)

  • Initial substrate: cholesterol

  • 2nd messenger system (cAMP)

  • Ultimately results in testosterone production

• Theca cells produce testosterone that diffuses into the granulosa cells

Granulosa cells have FSH receptors

• Activation of FSH receptors cause synthesis of aromatase, which is responsible for conversion of testosterone ——> estradiol

What are the function of estrogen

• Increased blood flow (hyperemia)

• Genital swelling (edema in vulva)

• Leukocytosis → leukocytes to submucosal region

  • Phagocytose foreign material during copulation

• Increased mucosal secretion

  • Lubrication, flush foreign material post-copulation

• Initiation of uterine gland growth, secretory activity

• Elevated myometrial tone (aid in sperm transport