Hormones controlling folliculogenesis and the menstrual cycle

lesson 4, week 9, unit 7

The HPG axis plays a central role in regulating the menstrual cycle, which consists of two major synchronized processes:

1. Folliculogenesis – The growth and maturation of ovarian follicles leading to ovulation.

2. Endometrial Changes – The thickening and preparation of the uterine lining for potential implantation.

3. Each cycle, hormonal communication between the hypothalamus, pituitary gland, and ovaries ensures that an egg is matured and released, and that the uterus is prepared for pregnancy.

Step-by-Step Regulation of the Menstrual Cycle by the HPG Axis

1. Hypothalamus Releases GnRH (Gonadotropin-Releasing Hormone)

• The hypothalamus releases GnRH in pulses, which travels to the anterior pituitary gland through the hypothalamic-hypopheseal portal system.

• The frequency of these pulses changes throughout the cycle, controlling the release of FSH and LH.

2. Pituitary Gland Releases FSH and LH

• Follicle-Stimulating Hormone (FSH):

  • Stimulates folliculogenesis, leading to the growth of several ovarian follicles.

  • One dominant follicle emerges and produces estrogen.

• Luteinizing Hormone (LH):

  • Works with FSH to mature the dominant follicle.

  • A sudden LH surge triggers ovulation, releasing the egg.

3. Ovaries Produce Estrogen and Progesterone

• Growing follicles release estrogen, which has two effects:

  • Stimulates the thickening of the endometrial lining to prepare for implantation.

  • Provides feedback to the brain to regulate FSH and LH levels.

• After ovulation, the empty follicle becomes the corpus luteum, which secretes progesterone:

  • Progesterone stabilizes the endometrial lining, making it receptive for a fertilized egg.

4. Feedback Loops Regulate the Cycle

• Negative Feedback: High estrogen and progesterone inhibit FSH and LH production to prevent multiple ovulations.

Estrogen’s Positive Feedback Loop on LH

During most of the menstrual cycle, estrogen provides negative feedback to the hypothalamus and pituitary, suppressing FSH and LH release. However, just before ovulation, estrogen briefly switches to a positive feedback loop, leading to the LH surge that triggers ovulation.

5. If Pregnancy Does Not Occur:

   • The corpus luteum breaks down, progesterone and estrogen levels drop, and the endometrial lining sheds (menstruation).

   • The cycle restarts, and the hypothalamus releases GnRH again.

LH surge that triggers ovulation.

1. As the dominant follicle matures, it produces high levels of estrogen.

2. When estrogen reaches a critical threshold (around day 12–14 of the cycle), it stimulates (rather than inhibits) the hypothalamus and pituitary.  It does this by acting on different neurons that have a positive effect on the hypothalamus and pituitary.

3. This positive feedback causes a rapid surge in LH, along with a smaller FSH increase.

4. The LH surge triggers ovulation, releasing the egg from the follicle.

5. After ovulation, estrogen drops, and progesterone from the corpus luteum restores negative feedback, suppressing further LH release.

This temporary positive feedback mechanism ensures that ovulation occurs at the right time in the cycle.

2 gonadotropin model

theca cells express LH receptors while the granulosa cells express FSH receptors. the theca cells in response to LH is they convert cholesterol into androgen precursors which then produces androgens like testosterone. the testosterone moves into the granulosa cells. in the granulosa cells have an enzyme (aromatase) which converts testosterone into estrogen. this is when the follicle really starts to produce high levels of estrogen needed in order to stimulate the LH surge

Hormones and how they affect the uterine lining.

Estrogen stimulates the thickening of the endometrial lining during the first half of the menstrual cycle, preparing the uterus for potential implantation. After ovulation, progesterone from the corpus luteum stabilizes the lining, but if fertilization does not occur, hormone levels drop, causing the endometrial lining to shed (menstruation).

How does the birth control pill take advantage of these hormonal regulations?

The combined birth control pill contains synthetic estrogen and progestin, which work together to prevent pregnancy by suppressing ovulation. The constant levels of estrogen and progestin provide negative feedback to the hypothalamus and pituitary, preventing the LH surge that triggers ovulation. Progestin also thickens cervical mucus, making it difficult for sperm to reach an egg, and thins the endometrial lining, reducing the chances of implantation. By maintaining stable hormone levels, the pill overrides the natural menstrual cycle and prevents the hormonal fluctuations needed for follicle development and ovulation. When taken correctly, it is highly effective, but missing doses can allow hormone levels to drop, potentially leading to ovulation and pregnancy.

Hormonal Changes in Menopause: How the HPG Axis is Affected

Menopause is the natural decline in reproductive hormones that occurs in people with ovaries, typically around the age of 45–55 years. It marks the end of ovulation and menstrual cycles. The changes in hormone levels occur because the ovaries stop responding to signals from the brain, primarily due to the depletion of ovarian follicles and reduced hormone production.

What Happens to Hormone Levels? Menopause

GnRH: Still released by the hypothalamus No major changes, but becomes less effective because the ovaries don’t respond to stimulation

FSH: Increases significantly Tries to stimulate the ovaries, but they no longer respond due to follicle depletion

LH: Increases significantly No ovulation occurs, despite the high levels

Estrogen: Decreases, Leads to symptoms like hot flashes, mood changes, and bone loss

Progesterone: Decreases, No ovulation means no corpus luteum, so less progesterone is produced

Why Do These Hormones Change? Menopause

As a person with ovaries ages, their ovaries become less responsive to FSH and LH due to the following reasons:

• People with ovaries are born with a finite number of follicles.

• Over time, most follicles are lost through ovulation and natural degeneration (atresia).

• By menopause, almost no functional follicles remain, so estrogen and progesterone production drops.

1. Loss of Estrogen & Progesterone Production

   • Since estrogen is produced by developing follicles, fewer follicles mean less estrogen.

   • Progesterone is produced by the corpus luteum (formed after ovulation), but since ovulation stops, progesterone levels drop too.

2. Why FSH & LH Increase but the Ovaries Don’t Respond

   • Normally, high estrogen provides negative feedback to the brain to regulate FSH & LH.

   • With low estrogen, this feedback loop fails, so the pituitary releases more FSH & LH to try to stimulate the ovaries.

   • However, the ovaries can’t respond because:

     • No functional follicles remain.

     • Ovarian cells become less sensitive to hormonal signals.

Effects of Menopause on the Body

The drop in estrogen and progesterone leads to several changes:

1. Hot flashes & night sweats – Due to the hypothalamus misinterpreting body temperature.

2. Irregular or absent periods – Ovulation stops, so menstrual cycles become irregular and eventually stop.

3. Bone loss (osteoporosis risk) – Estrogen helps maintain bone density, so its decline increases fracture risk.

4. Mood changes & sleep disturbances – Estrogen affects neurotransmitters in the brain, influencing mood and sleep.

5. Vaginal dryness & changes in skin – Estrogen maintains vaginal and skin elasticity, so its loss can cause dryness and thinning.