Endocrine 5

Female Reproductive System: Ovarian Function & Ovulation

Ovarian Role

• Principal functions of the ovaries include:

  • Production of mature eggs (ova)

  • Secretion of steroid hormones regulating the reproductive tract and sexual behavior

• At birth, ovaries contain a non-proliferating pool of approximately 2 million germ cells (oocytes).

  • At puberty, only ~400,000 ova remain.

• Oocytes surrounded by granulosa cells and a basement membrane form primordial follicles, the basic reproductive units of the ovary.

Follicular Growth

1. Initial Stages:

   • Primordial follicles begin growth towards primary follicles following an unknown stimulating event.

   • Growth is controlled by gonadotropins (FSH and LH) and steroid hormones until the follicles either ovulate or degenerate (astresia)

2. Primary Follicle Development:

   • Zona pellucida grows

   • Granulosa cells divide, increasing to two or more layers

   • Influenced by FSH and estrogen; FSH helps express LH receptors on granulosa cells.

3. Secondary Follicle:

   • Develops under FSH and LH influence, expressing receptors for these hormones and the appearance of a follicular antrum.

   • Granulosa cells produce follicular fluid, which expands the preovulatory follicle (Graafian follicle).

4. Theca Cell Development:

   • As the follicle matures, surrounding ovarian stroma differentiates into theca cells, which collaborate with granulosa cells to synthesize estrogen (exponentially).

Outcomes of Follicular Development

1. Follicular Atresia:

   • Usually, only one follicle ovulates; others undergo degeneration (atresia).

2. Ovulation:

   • Mechanism is unclear; possible factors include increased intrafollicular pressure and breakdown of the ovarian wall.

Post-Ovulation: Luteinization

• Ruptured follicle transforms into corpus luteum due to a rise in LH, which secretes progesterone and estrogens.

• Both theca and granulosa cells contribute to the corpus luteum, which temporarily produces estrogen and progesterone which thicken the endometrial wall and turn it to specialized tissue that allows the implantation of an embryo, respectively

• Without fertilization (in the absence of an implantation signal), the corpus luteum degenerates after a few days, leading to decreased hormone levels and initiation of the next reproductive cycle.

• If the corpus luteum implants, it becomes the corpus luteum of pregnancy and maintains the production of hormones

The Menstrual Cycle

• Endometrium thickens under estradiol's influence.

• Menses occurs on Day 1, marked by bleeding due to low estradiol and progesterone resulting in reduced blood supply to the endometrium.

Hormonal Changes

• Low estradiol and progesterone lead to increased FSH secretion from the pituitary and decrease in inhibin (which inhibits FSH release)

• A cohort of ovarian follicles is stimulated by FSH to develop, granulosa cells proliferate, producing estrogen, causing further granulosa proliferation

• By Day 8, one follicle becomes dominant, causing others to undergo atresia.

  • The dominant follicle produces increasingly more estradiol, stimulating uterine endometrium proliferation later in the cycle

• By day 13, the endometrium is very thick and estradiol induces production of endometrial progesterone receptors

• The ovaries produce androgens which are rapidly converted to estradiol by aromatase

Estradiol's Effects on the Brain and Pituitary

• Moderate estradiol concentrations:

  • Negative feedback on FSH release

  • Stimulate LH synthesis and increase pituitary sensitivity to GnRH.

• Elevated estrogen concentrations:

  • Induce an LH surge around Day 14, which facilitates ovulation.

  • Increase sensitivity of the anterior pituitary to GnRH, leading to increased LH synthesis by anterior pituitary known as estrogen positive feedback control mechanism

Contraception and Hormonal Regulation

• Oral contraceptives maintain moderate levels of estradiol and progesterone to prevent LH and FSH release, inhibiting ovulation with 99% success if taken correctly.

• The luteal phase lasts 14 days; if no fertilization occurs, hormone levels drop, leading to menstruation.

• Maintained nursing stimulates prolactin production, which inhibits the secretion of FSH and LH

  • This was used as birth control before the pill

Fertilization and Implantation

• Unfertilized egg is collected by the fimbria of the oviduct (fallopian tube) and transported to the lumen of the uterus.

• Once fertilization takes place, the egg begins dividing into a blastocyst, which later differentiates into a trophoblast (which becomes the placenta) and the inner cell mass (which becomes the embryo)

  • Fertilization typically occurs in the oviduct during the journey to the uterus, where the egg starts dividing.

• Around the time of implantation, trophoblast starts to synthesize human chorionic gonadotropin (HCG) which has LH-like properties. This is the signal that maintains the corpus luteum

  • HCG is what is tested on pregnancy tests

• After about the 12th week of pregnancy, the placenta becomes a autonomous endocrine organ, rendering the corpus luteum unnecessary

  • Together the placenta and developing fetus form the fetoplacental unit

Lactation

• Lactation refers to the secretion of milk, requiring normal mammary development under endocrine control.

• Hormones such as estrogen and prolactin are important for mammary gland development and milk production.

• Progesterone stimulates the growth of alveoli, where the milk is held

Nursing and Milk Production

• After childbirth, estrogen levels drop, but prolactin levels stay high

• Oxytocin induce uterine contractions during childbirth, meaning oxytocin is present right after childbirth

• Prolactin induces milk production while oxytocin causes milk ejection through its action on smooth muscle.

• Suckling

  • Decreases the production of dopamine (prolactin inhibiting hormone) in the hypothalamus, increasing prolactin secretion from the anterior pituitary

  • Increases oxytocin secretion from the posterior pituitary

• Composition of breast milk includes water, proteins, fats, carbohydrates, and antibodies.

• Infectious agents can be transmitted through breast milk.

Menopause

• Characterized by the loss of estrogen and progesterone production and depletion of follicles.

• Symptoms may include hot flashes and bone loss due to loss of estrogen

• High FSH levels indicate the onset of menopause and respond well to estrogen replacement therapy.