10-03-23 - Menstrual cycle & hormonal control Flashcards
Learning outcomes
- Define menarche and menopause
- Explain the role of gonadotrophic hormones in the development of ovarian follicles and the corpus luteum
- Describe the effects of FSH and LH in the early and mid-follicular phases of the menstrual cycle
- Describe the role of the corpus luteum in a normal menstrual cycle
- Describe the effects of oestrogen and progesterone on the menstrual cycle
- Describe other physiological effects of oestrogen and progesterone
- Explain the changes that occur in the endometrium during the menstrual cycle (follicular, secretory, menstrual phases)
What are the 3 physiological systems that regulate the female reproductive (menstrual) cycle?
- 3 physiological systems that regulate the female reproductive (menstrual) cycle:
1) Hypothalamic-pituitary-ovarian axis
2) Ovarian cycle (events in ovary)
* Follicular, Ovulation, Luteal
3) Endometrial cycle (events in endometrium)
* Menstrual, Proliferative, Secretory
How long does the human menstrual cycle last?
What is menarche?
When does it occur?
What does it mark the end of?
What is POF?
When can POF occur?
How can symptoms be treated?
- Menstrual Cycle length - mean 28 days (+/- 3.95) for about 40 years
- Menarche is defined as the first menstrual period in a female adolescent.
- Menarche typically occurs between the ages of 10 and 16, with the average age of onset being 12.4 years
- Menopause occurs around 45 - 55 yrs (average 51 yrs ) and marks end of natural fertility
- Menopause marks the “Exhaustion” of primordial follicles so primarily ovarian
- POF is Premature Ovarian Failure (POF)
- This is when menopause occurs in women under the age of 40 (idiopathic, autoimmune disorders, genetic disorders such as Fragile X, chemotherapy, radiation)
- Symptoms can be treated with oestrogen replacement (hormone replacement therapy – HRT)
Gonadotropin Levels Throughout Female Life.
What are gonadotropins?
Describe LH and FSH levels throughout the female life.
When do gonadotropin levels in females rise to very high levels?
What is required to suppress gonadotropin output in children and adolescents/adults?
- Gonadotropin Levels Throughout Female Life
- Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates
- LH and FSH peak during foetal life and again during early infancy, before falling to low levels throughout the rest of childhood.
- At the onset of puberty, LH and FSH levels slowly rise and begin to oscillate at regular monthly intervals.
- At menopause, gonadotropin levels rise to very high levels.
- In childhood very low sex steroid levels are sufficient to fully suppress gonadotropin output.
- In adolescence and adults higher levels of sex steroids are required to suppress gonadotropin release.
The Hypothalamic-Pituitary Axis.
What is another name for Gonadotrophin releasing hormone (GnRH)?
What is GnRH released by?
What is it secreted into?
Where does GnRH bind?
What does this lead to?
- The Hypothalamic-Pituitary AxiS
- Gonadotrophin releasing hormone (GnRH) is also known as luteinising hormone releasing hormone (LHRH)
- GnRH is secreted by small body neurons in arcuate nucleus & preoptic area of hypothalamus
- It is secreted into median eminence and hypophyseal portal system
- GnRH binds to receptors on gonadotophic cells of the anterior pituitary
- This binding leads to release of follicle-stimulating hormone (FSH) and luteinising hormone (LH)
How often do GnRH neurons release GnRH?
What is GnRH half-life in blood?
What family of compounds are FSH and LH from?
What receptors do theca and granulosa cells have?
Describe the diagram for the Hypothalamic-pituitary ovarian axis (in picture).
When is the feedback in this pathway positive/negative?
- GnRH neurons release GnRH in rhythmic pulses (about 1/hr)
- GnRH half-life in blood is 2-4mins
- Theca cells have LH receptors
- Granulosa cells have LH and FSH receptors
- Diagram for the Hypothalamic-pituitary ovarian axis (in picture)
- Most of the time, this pathway has a negative feedback, but just before ovulation, it swithces to a positive feedback system, leading to an LH surge
6) Describe processes in the menstrual cycle in the following days:
1) Day 1-7
2) Day 7-14
3) Day 14
4) Day 14-25
- Processes in the menstrual cycle in the following days:
1) Day 1-7: multiple follicles develop, by Day 7 one follicle becomes dominant
2) Day 7-14: Dominant follicle develops
3) Day 14: Ovulation
4) Day 14-25: corpus luteum develops/functions, degenerates between Day 25-28
Describe the changes in the following hormone concentrations during the menstrual cycle:
1) FSH
2) LH
3) Oestradiol
4) Progesterone
5) Inhibin
- Changes in the following hormone concentrations during the menstrual cycle:
1) FSH
* Increases in early part of follicular phase, then steadily decreases throughout remainder of cycle except small mid-cycle peak
2) LH
* Constant most of follicular phase, then large midcycle increase (LH surge) peaking ~18h before ovulation Then rapid decrease with further slow decline during the luteal phase
3) Oestradiol
* Low and stable for 1st week, increases rapidly in 2nd week, starts to decline before LH peak.
* Second increase due to corpus luteum in last few days of cycle
4) Progesterone
* Low level due to ovary release during follicular phase with small increase just before ovulation.
* Soon after ovulation, large increase due to corpus luteum formation, then similar pattern to oestrogen
5) Inhibin
* Similar pattern to oestrogen ie increases in late follicular phase, remains high during luteal phase, decreases as corpus luteum degenerates
What is the endometrial cycle?
What occurs during this cycle?
What happens during the secretory phase?
What denotes day 1 of the menstrual cycle?
What change in body temperature do we see during ovulation?
- The endometrial cycle is the portion within the menstrual cycle that has to do with the endometrium, the lining of the uterus
- During this cycle, an environment needs to be created that allows for a fertilised egg to implant
- During the secretory phase, there is secretion of substances that produce a good environment for a fertilised egg to develop before the placenta develops
- The first day of menstrual bleeding denotes day 1 of the menstrual cycle
- There is a discernible increase in body temperature (1oF or 0.5oC) at ovulation
Where are theca cells located? What type of receptors do they have?
What is their role?
Where are granulosa cells located?
What happens to this layer of cells during follicle development?
What receptors do granulosa cells have?
What is their role?
How do granuloma and theca cells compare to Sertoli and Leydig cells?
- Theca cells are located on the superficial layer of follicle
- They have LH receptors
- Theca cells convert cholesterol to pregnenolone
- They also produce androstenedione and testosterone
- Theca cells are equivalent to Leydig cells in males.
- Granulosa cells are located deep to the follicle
- This layer increases in size markedly during 1° to 2° follicle development due to granuloma cells multiplying
- Granulosa cells have LH and FSH receptors
- They also convert cholesterol into pregnenolone + activate aromatase
- Granulosa cells are homologous to the Sertoli cells of the testis (similar in position, structure, and evolutionary origin but not necessarily in function)
When does the concentration of FSH in the blood rise to its maximum?
What does it stimulate in the first week of the follicular phase?
When do granuloma cells express FSH receptors?
How do levels of LH fluctuate during the menstrual cycle?
What is the role of LH during the secretory phase of the menstrual cycle?
Why do LH levels rise 12 hours before ovulation?
- FSH
- The concentration of FSH in the blood rises to its maximum during the follicular phase of the menstrual cycle.
- In the first week of the follicular phase, it stimulates the growth of medium sized follicles.
- Granulosa cells of the ovary express FSH receptors during the follicular phase of the menstrual cycle.
- LH
- The levels of LH vary during the follicular and secretory phases of the menstrual cycle.
- During the secretory phase of the menstrual cycle, LH stimulates steroid hormone synthesis by the corpus luteum
- 12 hours before ovulation LH rises dramatically, stimulated by an increasing rate of secretion of oestrodiol-17β.
Feedback of Ovarian Steroids.
What is the role of Oestrogen and progestins during most of the menstrual cycle?
When does positive feedback occur?
How does this occur?
What will this lead to?
- Feedback of Ovarian Steroids
- During most of the menstrual cycle, oestrogen and progestins have negative feedback on pituitary and hypothalamus, which reduces LH and FSH production
- Positive feedback occurs near ovulation (end of follicular phase)
- This occurs when Oestradiol levels gradually increase after reached a certain threshold for a min of 2 days, Hypothalamic-pituitary ovarian axis reverses its sensitivity to oestrogens
- Leads to oestrogen positive feedback and an increased sensitivity of anterior pituitary to GnRH leads to LH surge, which triggers ovulation
Hypothalamic-pituitary ovarian axis diagram
What are Activins, Inhibins & Follistatins produced by?
What is their role?
- Activins, Inhibins & Follistatins are peptide hormones produced by the ovaries
- They selectively affect FSH production and secretion:
1) Inhibins (inhibit FSH)
* Inhibins specifically reduce FSH mRNA levels, do not affect LH mRNA levels
2) Activins (activate FSH)
* Activins specifically increase FSH mRNA levels, do not affect LH mRNA levels
3) Follistatins (bind to activins inactivating them, so inhibiting FSH)
What are 6 locations of action of oestradiol?
- 6 locations of action of oestradiol:
1) Prepare female reproductive tract for fertilisation and implantation
2) Induces expression of progesterone receptors in target tissues
* Required for corpus luteum to work
3) Tubal epithelium – Stimulates proliferation of epithelial lining
* Secretes sugar-rich fluid (can be used by sperm mitochondria for energy)
4) Endometrium
* Stimulates hyperplasia and hypertrophy of epithelial lining
* Glands elongate and spiral arteries grow
5) Smooth muscle
* Up regulates receptors for prostaglandins and oxytocin
* Spontaneous activity increased
6) Cervix
* Increases mucous volume (allows sperm to swim through)
* Decreases mucous viscosity
