HPO Axis and Uterine Phases Quiz

Hypothalamus-Pituitary-Ovary (HPO) Axis and Uterus

• The HPO axis includes the hypothalamus, pituitary gland, and ovaries.
• The uterus is a critical reproductive organ.
• The menstrual cycle can be understood through changes in the uterus.
• The follicular phase is equivalent to the proliferative phase (uterine perspective).
• The luteal phase is equivalent to the secretory phase (uterine perspective).

Follicular Phase (Proliferative Phase)

• Characterized by estrogen's growth-promoting effects.
• Estrogen stimulates growth of the uterine lining (endometrium).
• Promotes growth of blood vessels within the endometrium.
• Encourages growth of glands within the uterus.
• Prepares the uterus for possible pregnancy after ovulation.
• The non-pregnant uterus has a thin lining that thickens during each cycle.
• This phase supports growth of endometrium, blood vessels, and glands.

Luteal Phase (Secretory Phase)

• Characterised by increased glandular activity and secretion in the uterus.
• Uterine glands secrete nutrients to support a fertilized embryo if conception occurs.
• Progesterone promotes secretion from these endometrial glands.
• These effects occur regardless of pregnancy, but prepare the uterus for pregnancy.

Menstruation

• At the end of the luteal phase, the drop in estrogen and progesterone causes the endometrial lining to break down.
• The endometrium, blood supply, and glands are shed.
• Menstruation is the combined tissue and blood loss.
• Each month, changes in hormones, follicular development, and uterine cycles happen.

Endometrial Changes (Diagram)

• The endometrium thickens during the follicular phase due to cell proliferation and blood vessel growth.
• The luteal phase shows increased secretion, but no further layer growth.
• Corpus luteum regression leads to endometrial shedding and menstruation.
• The first day of menstruation marks the start of the menstrual cycle and follicular phase.
• This triggers an increase in FSH, restarting follicular development.

Ovarian and Uterine Phases

• The ovarian and uterine phases are linked.
• Key hormones regulate these phases.
• Events during each phase are distinct:
  • Early cycle (Follicular Phase/Proliferative Phase): Characterized by estrogen production which causes endometrial growth, blood vessel growth, and gland formation.
  • Mid-cycle (Ovulation): Ovum release and corpus luteum formation, not a phase but a transition.
  • Late cycle (Luteal Phase/Secretory Phase): Progesterone and estrogen cause glandular secretion.
  • End of cycle: Transition to follicular phase, menstruation, and hormonal withdrawal.

Estrogen Action at Puberty

• Estrogen is not essential for fetal reproductive organ development.
• Fetal feminization depends on the absence of male hormones.
• During puberty, estrogen influences:
  • Uterus, vagina, and fallopian tube growth.
  • Secondary sex characteristics (fat distribution, breasts, genitals).
  • Bone growth, with androgens from the adrenal gland, leading to earlier epiphyseal closure in females.
• Males produce estrogen locally in bones; females have more circulating estrogen.

Estrogen and Progesterone in Adults (Reproductive Tract)

• Estrogen:
  • Induces endometrial proliferation (blood vessels, glands).
  • Maturation of vaginal epithelium.
  • Causes clear cervical mucus.
  • Maintains progesterone receptors.
• Progesterone:
  • Stimulates endometrial and fallopian tube gland secretions.
  • Secretion of thick cervical mucus (inhibiting sperm penetration).
  • Decreases myometrial estrogen receptors (not endometrial).

Estrogen and Progesterone Effects Outside the Reproductive Tract

• Brain:
  • Estrogen inhibits GnRH, LH, and FSH.
  • Affects brain development, serotonin, and mood (positive and negative effects).
  • Potential protective effects on responses to neural injury.
  • Progesterone may also affect mood and neural responses.
• Body Temperature: Progesterone increases body temperature.
• Cardiovascular System: Estrogen influences blood pressure (vasodilation), blood flow to the uterus, and indirect protection.
• Liver:
  • Estrogen increases production of binding globulins (SHBG, TBG, CBG).
  • Increases angiotensinogen production.
  • Decreases cholesterol and LDL, increases HDL.

Menopause

• Menopause may result from follicle depletion and/or reduced brain responsiveness.
• Ovarian estrogen production, particularly estradiol, decreases.
• Estradiol levels drop, but some estrogen production from stromal tissue remains.
• Aromatase levels also decrease.
• Androgen-to-estrogen ratio increases, but some estrogen remains.
• The adrenal gland produces androgens (DHEA, androstenedione), which can convert to estrone.
• Estrone acts on estrogen receptors.
• Adrenal and fat tissue produce estrogen.
• Aromatase in fat isn't regulated by FSH like in the ovary.
• Lower estradiol leads to increased LH and FSH.

Consequences of Reduced Estrogen and Progesterone After Menopause

• Estrogen and progesterone levels decrease, but not to zero.
• Decreased estrogen leads to atrophy of estrogen-dependent tissues.
• Menopause symptoms vary, including: vaginal dryness, mammary atrophy, osteoporosis, urinary incontinence, hot flashes, and increased risk of depression and coronary heart disease.
• Increased LH and FSH due to reduced feedback.

Summary of Key Concepts

• The menstrual cycle relies on interactions between hypothalamic, pituitary, and ovarian hormones, with both positive and negative feedback loops.
• Ovum production involves a dominant follicle with high aromatase/estrogen production.
• Follicular/proliferative phase is characterized by estrogen.
• Luteal/secretory phase is characterized by progesterone and estrogen.
• Estrogen supports diverse systems (reproductive tract, breasts, brain, bone, and cardiovascular system).
• Post-menopause changes in estrogen have associated risks.

Comparison of Follicular and Luteal Phases