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4/ RED > HPG Axis > Flashcards

HPG Axis Flashcards

1
Q

What is the HPG axis in women?

A

hypothalamus (GnRH) –> a. pituitary (LSH/FH) –> ovary (oestrogen/progesterone)

  • oestrogen provides negative/positve feedback to a.pituitary
  • progesterone provides negative feedback to a/pituitary
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2
Q

What is the HPG axis in men?

A

hypothalamus (GnRH) -> a. pituitary (FSH/LH) –> testis (inhibin and testosterone)
- inhibin and testosterone provide negative feedback to a. pituitary

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3
Q

What is the hypothalamus?

What does it control?

A

region found at the base of the brain between midbrain and forebrain
collection of brain nuclei or centres
controls endocrine function via pituitary gland

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4
Q

What is the hormone released from the hypothalamus on the HPG-axis?

A

GnRH

gonadotropin releasing hormone

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5
Q

What type of hormone is GnRH?

What is Kallmann Syndrome?

A

a peptide hormone. decapeptide, from a 92 aa prepropeptide

Kallmann Syndrome = failure of GnRH secreting neurones to migrate during development –> infertility

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6
Q

What kind of GnRH secretion triggers gonadal activation

A

pulsatile GnRH secretion at puberty

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7
Q

What is the effect of continuous GnRH secretion?

A

leads to down regulation of GnRHR on surface of gonadotroph cells - no stimulation of FSH/LH release

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8
Q

It is possible to block GnRH effects using an antagonist and an agonist. TRUE/FALSE

A

TRUE

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9
Q

What is secreted by the pituitary gland?

A 
LH/FSH
GH
ACTH
FSH
Prolactin

ADH
oxytocin

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10
Q

What are the 3 gonadotropins?
What kind of hormones are they?
How do they interact with their target cells?

A

FSH LH hCG
glycoproteins
bind receptors on cell surface and signal via GPCRs

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11
Q

LH:

  • what is it secreted by?
  • what cells does it act on? where are these cells?
  • what is its structure?
  • what is its receptor?
A
  • gonadotrophs (a. pituitary)
  • leydic cells (testis), theca/granulosa cells (ovary)
  • common alpha chain, unique B chain, one carb chain
  • LHCGR
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12
Q

FSH:

  • what is it secreted by?
  • what does it act on?
  • what is its structure?
  • what is its receptor?
A
  • gonadotrophs (a.pituitary)
  • sertoli cells (testis), granulosa cells (ovary)
  • common alpha chain, unique B chain, two carb chains
  • FSHR
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13
Q

hCG:

  • what is it secreted by?
  • what does it act on?
  • what is its structure?
  • what is its receptor?
A
  • trophoblast cells (embryo)
  • luteal cells (corpus luteum)
  • common alpha chain, unique B chain, two carb chains
  • LHCGR
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14
Q

What are the two forms of communication between the hypothalamus and pituitary?

A

Direct i.e. neural to posterior pituitary

Indirect i.e. vascular to anterior pituitary

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15
Q

Where are all sex steroids derived from? and via?
What are the characteristics of sex steroids?
What do they act on?
What are they bound to in the blood?

A

all derived from cholesterol (via acetate)
lipid soluble, nuclear receptors
act via steroid response elements (SREs)
bound to carrier proteins - albumin, sex hormone binding globulin (SHBG), androgen binding protein (ABP)

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16
Q

What are the 3 families of sex steroids?

What are they responsible for?

A

progestogens - pregnancy (plancenta/ovary)
androgens - maleness
oestrogens - femaleness (liver, adrenals, adipose, placenta)

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17
Q

What is the order of cleavage for the 3 classes of sex hromenss?

A

progestogens
androgens
oestrogens

18
Q

What are the 3 progestogens?

A

Progesterone (P4)
17a-hydroxyprogesterone (17a-OHP)
20a-hydroxyprogesterone (20a-OHP)

19
Q

What are the reproductive functions progestagens?

A
  • preparation of uterus
  • maintenance of uterus during pregnancy
  • growth of mammary glands
  • suppression of lactation
  • catabolic effects
  • regulation of gonadotrophin
20
Q

What are the receptors for progestagens?

A

PR-A and PR-B

activate different genes

21
Q

What are the 4

androgens?

A

5a-dihydrotestosterone (DHT)
testosterone (T)
androstenedione (A4)
dehydroepiandrosterone (DHEA)

22
Q

What are the reproductive functions of androgens?

A
  • development and maintenance of male reproductive system
  • secondary sexual characteristics
  • sexual function
  • support spermatogenesis
  • regulation of gonadotrophins
23
Q

What are the receptors for androgens?

A

AR

polymorphoc in exon 1 with isoforms showing differing sensitivities to androgen levels

24
Q

What are the 3 oestrogens?

A

oestradiol 17B (E2)
oestriol (E3)
oestrogen (E1)

25
Q

What are the reproductive functions of oestrogens?

A
  • secondary sexual characteristics
  • stimulate growth and activity of mammary glands
  • stimulation proliferation of endometrium fro progesterone action
  • regulate gonadotropins
26
Q

What are the receptors for oestrogens?

A

ERalpha and ERbeta

27
Q

Which of the 3 oestrogens are dominant in each of the following:

  • puberty to menopause
  • pregnancy
  • post-menopause
A
  • puberty to menopause = oestradiol
  • pregnancy = oestriol
  • post-menopause = oestrone
28
Q

What determines potency?

A

depends on how well steroid ‘fits’ binding site on receptor

29
Q

Some steroids fit receptors from other classes. Give an example

A

synthetic progestogens in contraceptive pill can be androgenic - side effects e.g. acne

30
Q

Some steroids bind but don’t activate. Give an example

A

act as antagonists e.g. Mifepristone (RU486)

- anti-progestogen / abortion pill

31
Q

In what two ways can steroid action be regulated?

How does this affect measuring hormone levels?

A
  1. alter amount of steroid produced
  2. alter amount or structure of receptor
    - sex steroids are both regulated by and regulate gonadotrophin of the anterior pituitary via feedback loops
    - only measuring hormone levels will not give complete picture
32
Q

What is central hypogonadism?

What is primary hypogonadism?

A

central - hypothalamus/pituitary –> low FSH/LH

primary - ovary/testis –> high FSH/LH

33
Q

Why is GnRH rarely measured?

A

pulsatile and short halflife

34
Q

What are the functions of prolactin?

A
  • stimulates milk production
  • inhibits gonadal activity through central suppression of GnRH (and thus decreased LH/FSH) –> induces lactational amenorrhea
35
Q

What are the 3 phases of the menstrual cycle?

A

follicular/proliferative
ovulation
luteal/secretory

36
Q

What is the normal duration of the menstrual cycle?
What is the normal duration of luteal phase?
When is Day 1?
When is FSH/LH tested for?
When is ovulation tested?

A 
26-32 days (28 days)
14 days
first day of menses
day 2 or 3
P4, tested on day 21
37
Q 
What is oligomenorrhea?
What is primary amenorrhea?
What is secondary amenorrhea?
What is menorrhagia?
What is dysmenorrhea?
A 
irregular periods
no bleed ever
no bleed in last 6 months 
heavy periods 
painful periods
38
Q

What is menopause?

A

females are born with a finite number of oocytes
around the age of 50, ovarian reserve is depleted and ovulation ceases
no production of progesterone or oestrogen by ovary
removal of negative feedback leads to high FSH/LH levels

39
Q

How does hormonal contraception work?

A

synthetic progestogens and oestrogens - suppresses ovulation, thickens cervical mucus, thin endometrium

40
Q

How does fertility treatment work?

A

IVF –> ovarian stimulation

down regulate HPG axis with GnRH agonist/antagonist. stimulate with FSH, induce oocyte maturation with hCG

41
Q

What is the treatment for prostate cancer?

A

GnRH antagonists to suppress T production

4/ RED (19 decks)

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