HPG Axis

Question 1

GnRH

Answer 1

Released by hypothalmus after puberty>gonadotroph cells of ant pituitary>gonadatrophophin (LH/FSH)
Peptide hormone (10 amino acids) cleaved from larger prepropeptide
Release = pulsatile (90min intervals) 
Continuous release > down reg GnRH receptors on surface of gonadtroph cells > no stimulation for release of LH/FSH
Use  GnRH agonist/ antagonist to shut down HPG axis

Question 2

Pituitary

Answer 2

Release hormones in response to hypothalmic signals and -ve feedback loops
Ant pituitary - ACTH from coritcotrophs, GH from somatotrophs, Prolactin from lactotrophs, FSH & LH from gonadotrophs, TSH (not important for reproduction)
Post pituitary - Oxytocin and ADH(not imp for for reproduction)

Question 3

LH

Answer 3

Secreted by: gonadotrophins
Acts on: Leydig cells (testes), theca and granulosa cells (ovaries - oocyte release)
Structure: common alpha chain, unique beta, one carbohydrate chain
Receptor: LHCGR (same receptor as hCG)

Question 4

FSH

Answer 4

Secreted by: gonadotrophins
Acts on: Sertoli cells (testes), granulosa cells (ovaries - oocyte maturation)
Structure: common alpha chain, unique beta, two carbohydrate chain
Receptor: FSHR

Question 5

hCG

Answer 5

Secreted by: synctiotrophoblasts cells (embryo)
Acts on: Luteal cells (ovary)
Structure: common alpha chain, unique beta, two carbohydrate chain
Receptor: LHCGR (same receptor as LH - beta chain similar but slightly longer)

Question 6

What cells does FSH act on?

Answer 6

Sertoli cells in the testes and the granulosa cells in the ovaries

Question 7

What will continuous release of GnRH cause?

Answer 7

> down reg GnRH receptors on surface of gonadtroph cells > no stimulation for release of LH/FSH

Question 8

How does the hypothalmus communicate with the pituitary?

Answer 8

Indirect: Parvocellular neurones > GnRH > axons > primary portel plexus > ant pituitary gonadotroph cell > LH + FSH

Direct: Neural to post pituitary

Question 9

What is Kallman Syndrome?

Answer 9

Failure of GnRH secreting neurones to migrate during development > infertility as gonadotrophs cannot be secreted

Question 10

How does the HPG axis differ in men and women?

Answer 10

Testis secretes testosterone > -ve feedback to an pituitary and hypothalmus & inhibin > -Ve feedback to ant pituitary only
Oesterogen > -ve/+ve feedback loop to ant pituitary AND hypothalmus & Progesterone > -ve feedback to both also

Question 11

What are sex steroids derived from?

Answer 11

Cholesterol via acetate and secreted via gonads, adrenal glands, liver and adipose tissue

Question 12

What are the types of sex steroid?

Answer 12

Progestagens - pregnancy (21C) >enzymes>Androgens - maleness (19C) > Oestrogens - femaleness (18C)

Question 13

Describe the progestagens from most potent to least

Answer 13

Progesterone (P4) - prepares and maintains uterus for pregnancy
17a-OHP - growth of mammary glands
20a-OHP - suppress lactation, catabolic effects and regulates gonadotrophins
All act on PR-A and PR-B receptors and are able to induce to different effects by activating different genes

Question 14

Describe the androgens from most potent to least

Answer 14

5a-testosterone (DHT) - development and maintenance of male reproductive system
Testosterone (T) - development of secondary sexual charcateristics
Androstenedione (A4) - supports sexual function
DHEA - regulates gonadotrophins and supports spermatogenesis
All act on AR (androgen receptor) which are very polymorphoic

Question 15

Describe the oestrogens from most potent to least

Answer 15

Oestradiol 17 beta - secondary sexual characteristics and growth of mammary glands (dominant from puberty to menopause)
Oestriol - stimulates proliferation of endometrium for progesterone action (dominant in pregnancy)
Oestrone - regulates gonadotrophins (dominant after menopause)
Act on ER alpha and beta receptors

Question 16

How does Mifepristone (RU486) work?

Answer 16

Anti-progestagen, anatagonist causing abortion

Question 17

Why do you get SE e.g. acne from progestagen contraceptive pills?

Answer 17

Sex steroids can bind to receptors from other classed e.g. progestagens can be androgenic > acne

Question 18

What determines the potency of sex hormones?

Answer 18

how well they can bind with their receptors (varies within each class)

Question 19

How are sex steroids carried and how do they act?

Answer 19

Lipid soluble therefore carried by proteins in the blood e.g. albumin, SHBG (produced mainly in liver but also at other sites), ABG ( testes produced SHBG)
Act on:
Classical pathway > nuclear receptors (steroid response elements)
Non-classical > cell membrane receptors

Question 20

How are sex steroids regulated?

Answer 20

Altering amount of steroid produces/structure of receptor
> just measuring hormone levels will not give full picture
Also regulate and are regulated by feedback loops (issues with this (primary/central hypogonadism > fertility issues - more common in women than men)

Question 21

Central hypogonadism

Answer 21

Problem with feedback loops at level of pituitary - LH and FSH levels low

Question 22

Primary hypogonadism

Answer 22

Problem with feedback loops at level of gonads - LH and FSH high

Question 23

Prolactin

Answer 23

Increased in pregnancy and during breastfeeding
Centrally suppresses GnRH > Reduced LH and FSH
Lacteal amenorrhea - natural contraceptive (98% effective at preventing pregnancy straight after childbirth)
No -ve feedback

Question 24

Gametogenesis in males v females

Answer 24

M: Continuous
F: cyclic (around 1 oocyte released per month), finite number of oocytes > around 50, ovarian reserve depleted > Menopause

Question 25

Menopause

Answer 25

Ovarian reserve depleted, no longer production of progesterone/oestrogen by ovary > removal of -ve feedback loop > high levels of LH and FSH Diagnosis - test FSH/LH levels, if FSH high > indication close to entering menopause

Question 26

What are the phases of the menstrual cycle?

Answer 26

Normally last 26-32 days (variation from difference in follicular phase) 1) follicular/proliferative phase - generally 14-20 days starting day from from 1st day of menses (oestrogen and LH increase) 2) Ovulation - typically day 14 - Levels of LH and FSH peak just prior and oestrogen begins to decrease. 3) Luteal/secretory phase - always 14 days long. Levels of progesterone increase

Question 27

When is the fertile period?

Answer 27

Oocyte viable 24h and sperm for 5 days | Ovulation in the middle of the luteal phase (around day 21) - can test for high levels of P4 for this

Question 28

Oligomenorrhea

Answer 28

< 9 cycles in 12 months

Question 29

Amenorrhea

Answer 29

primary - never | secondary - ceased (no bleed in previous 6 months)

Question 30

How can HPA axis be used?

Answer 30

``` Hormonal contraceptives - Synthetics progesterones and oestrogens suppress ovulation, thicken cervical mucus and thin endometrium Fertility treatment (IVF/ICSI) - stimulation of oocyte production and hCG stimulate maturation Down-regulation via GnRH agonist (down regulation of GnRH receptors) Stimulation oh HPG axis via FSH Prostate cancer treatment - GnRh agonist (down reg receptors) to suppress testosterone production ```