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RED > HPG Axis > Flashcards

HPG Axis Flashcards

1
Q

GnRH

A 
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
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2
Q

Pituitary

A

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)

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3
Q

LH

A

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)

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4
Q

FSH

A

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

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5
Q

hCG

A

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)

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6
Q

What cells does FSH act on?

A

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

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7
Q

What will continuous release of GnRH cause?

A

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

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8
Q

How does the hypothalmus communicate with the pituitary?

A

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

Direct: Neural to post pituitary

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9
Q

What is Kallman Syndrome?

A

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

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10
Q

How does the HPG axis differ in men and women?

A

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

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11
Q

What are sex steroids derived from?

A

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

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12
Q

What are the types of sex steroid?

A

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

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13
Q

Describe the progestagens from most potent to least

A

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

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14
Q

Describe the androgens from most potent to least

A

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

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15
Q

Describe the oestrogens from most potent to least

A

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

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16
Q

How does Mifepristone (RU486) work?

A

Anti-progestagen, anatagonist causing abortion

17
Q

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

A

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

18
Q

What determines the potency of sex hormones?

A

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

19
Q

How are sex steroids carried and how do they act?

A

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

20
Q

How are sex steroids regulated?

A

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)

21
Q

Central hypogonadism

A

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

22
Q

Primary hypogonadism

A

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

23
Q

Prolactin

A

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

24
Q

Gametogenesis in males v females

A

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

25
Q

Menopause

A

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

26
Q

What are the phases of the menstrual cycle?

A

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

27
Q

When is the fertile period?

A

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

28
Q

Oligomenorrhea

A

< 9 cycles in 12 months

29
Q

Amenorrhea

A

primary - never

secondary - ceased (no bleed in previous 6 months)

30
Q

How can HPA axis be used?

A 
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

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