Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Science of Repro > GnRH > Flashcards

GnRH Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

GnRH background (3-5)

A
  • Master controller of reproduction
  • Characterised in 1971
  • Gene on chromosome 8
  • 23 isoforms in vertebrates
  • Most vertebrates- GnRH I (GnRH) and GnRH II
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

GnRH roles: (4)

A

Roles include:
* Neuroendocrine - HPG
* Paracrine (placenta/gonads)
* Autocrine (prostate/breast cancer)
* Neurotransmitter (Regions of the brain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

GnRH Structure (3)

A
  • peptide - initially synth. as pre-pro hormone
  • Cleavage steps-= Mature GnRH and GAP
  • GAP peptide- co-secreted with GnRH, unknown function
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The migratory path of GnRH neurones (3)

A
  • Embryonic period: Originate (outside CNS) in medial olfactory placode
  • Cells migrate: (Nasal region = brain = medio-basal) hypothalamus

*Numerous
genes involved

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Known mutations causing HH

A

HH due to regulatory gene mutations:

KAL1, FGFR1, FGF8, PROK2, PROKR2, NELF, CHD7,
GNRH1, GNRHR, GPR54, TAC3, TAC3R, NKB/NK3R, WDR11.

Kallmann Syndrome
» Mutation in KAL-1 gene
» Premature termination of migration
= anosmia & hypogonadotrophic hypogonadism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

GnRH release (7)

A

1) GnRH is processed and packaged into storage granules

2) transported down the
axons to external zone of the median eminence + released in synchronized
pulses from the GnRH nerve endings into hypophyseal portal system.

  • Rhythmic pulses- every 30-120 minutes – “circhoral pulses”
  • GnRH Pulse generator
    – collection of hypothalamic neurons producing endogenous secretory rhythms
  • GnRH - 2-4 minutes = v short 1/2 life = degraded v quickly
  • GnRH stimulates synthesis and secretion of gonadotrophins.
  • Differential frequency and amplitude alter pattern of FSH and LH secretion, therefore impact gonadal response.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

GnRH receptor (5)

A
  • G-protein-coupled receptor (GPCR)
  • Two variants Type I and II GnRHR
  • Type 1- full length, Type 2 - missense truncation (humans - mRNA expressed + transcribed but protein receptor isn’t correct)
  • absence of carboxyl terminal tail = Resistant to desensitisation (some exceptions) (evolutionary benefit)
  • Expressed on gonadotroph cells of anterior pituitary
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does GnRH regulate Gonadotrophin production? (5)

A

1) binds to Glycoproteins with α & β chains (LHr + FSHr)
= sec. of FSH, LH, GnRH

2) Rhythm & pulsatility of GnRH:
- Slow frequency or low amp GnRH pulse ⇒ ⇧FSHb gene
expression
- Fast frequency GnRH pulse ⇒ ⇧LHb transcription
– Determines dimerisation of subunits (coming together to form hormone)
– Determines glycosylation (addition of sugar residues)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

GnRH & gonadotrophins (male) - variance (3)

A

-GnRH pulses – constant frequency every 2hr

  • amplitude will vary over period of time, despite regular pulse (consistent presence)

~15% of normal men w/mean testosterone levels in
normal range had considerable variability in LH pulses & low serum T recordings

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

GnRH & gonadotrophins (female) - cyclical differences (3)

A

»Higher + faster frequency GnRH pulse (every 30min) = favours LH secretion

> > Cyclical pulses bought about by menstrual cycle

»Lower frequency/amplitude GnRH pulse (every 90-120min) = favours FSH
synthesis and secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does GnRH differentially regulate FSH + LH production? - Anovulatory phenotype in female DKO (ERK1/2-/-) mice (4)

A
  • prominent study - ERK signalling(crucial for LH secretion) in pituitary required for females not male fertility

-ERK knockout mice: injected saline + monitored menstrual cycle (epithelial cell count)

=CLEAR DISRUPTION IN MC compared to control (downreg. of LH - FSH not really effective -> largely constitutive element, and no ovulation)

-LHbeta expression is decreased because of ERK-MAPK needed for LHbeta transcription + translation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

MoA ERK + LHb (6)

A

1)GnRHR
2)G-alphaS + G-alphaq/11
3) PKA + PKC
4) ERK1/2
5)Egr1 (upreg.)
6) LH-Beta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Differential GnRH receptor signalling summary - High/Faster GnRH: (LH +FSH) (6)

A

images

1) GnRH binds to receptor = GQ signalling
2) Activates ERK1/2 pathway = (upreg. Egr1)
3)Egr1 binds to promoter on LHb gene = upreg. of LHb

1) GnRH binds to receptor = GQ signalling
2) Activates ERK1/2 pathway = (upreg. ICER)
3) = Inhibiting FSH transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Differential GnRH receptor signalling summary - Low/Slow GnRH: (LH + FSH) (5)

A

1) GnRH binds to receptor = GQ signalling
2) Activates ERK1/2 pathway = (upreg. Egr1) - but not enough because of low pulses

1) GnRH binds to receptor = GQ signalling
2) Activates ERK1/2 pathway + CREB pathway (cAMP-> PKA->)
3) binds to FSHb gene (because of no ICER) = upreg. of FSHb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

GnRH and menstrual cycle

A

(1) Early Follicular
phase – pulses slow
(every 90-120mins)
»FSH

(2) Mid-late F phase
– pulse freq increases
(every hr.) »LH

(3) After ovulation –
pulses slow (every 3-
5h) »FSH production

(4) End of luteal phase
– increase in GnRH pulse
secretion » FSH release

images

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Feedback by gonadal steroids (male) (3)

A

In MALES:

LH: driver of Testosterone from Leydig cells-> -tve feedback reduces LH secretion (Rhesus monkey
experiments )

FSH:
– Inhibin ↓FSH secretion from pituitary
– Activin ↑FSH secretion from pituitary

17
Q

Feedback by gonadal steroids (female) (5)

A

In FEMALES through most of
menstrual cycle:
GnRH -> FSH/LH -> oestr./ Proges. - uses -ve feedback except OVULATION

-Proges. & low plasma oestr. = -tive feedback
= (Net effect) reduced LH & FSH

-High sustained (48h) plasma [E2] = enhanced LH & FSH = +ve feedback

*P4 feedback = ↓GnRH pulse freq
*E2 feedback =↓GnRH pulse amplitude

18
Q

Where is the site of feedback? (3)

Is it direct/indirect action? (2)

(5)

A

Where would the site of steroid feedback be?
»Either anterior pituitary or hypothalamus
»Oestr. & proges. receptors on both
»Inhibin receptors found only in pituitary

How would this occur?
»In anterior pituitary by direct reg. of GnRHR
»In hypothalamus by directly affecting GnRH neurones or indirectly by changing activity of other neural system that influence GnRH release (e.g. kisspeptin)

19
Q

Evidence of Steroid feedback site -pituitary (4)

A

Rhesus Monkeys:
1) created lesions in hypo. (= X GnRH) + carried out Ovx (= X steroids: downreg. FSH +LH)

2) exogenous GnRH pulses = anterior pituitary created pulses of FSH +LH

3) exogenous E2 injection = downreg. FSH + LH (= -ve feedback)

4)increased E2 (mimic +ve feedback) = FSH + LH surge

PROOF

20
Q

Mechanisms of feedback - Pituitary (4)

A

Positive feedback:
-E2 induces & maintains GnRHR by increasing GnRHR mRNA in pre-ovulatory phase
-E2 sensitises “self-priming” effect i.e. enhances interaction b/w GnRH & GnRHR

Negative feedback:
(-E2 ??
-Inhibin?? (they may affect the stability of GnRHR - not confirmed)

-Progesterone ↓ GnRHR mRNA, also evidence of P4 response element in GnRHR gene

21
Q

Evidence of Steroid feedback site - hypothalamus (4)

A

1) Ovx sheep
2) large boluses of E2
3) canulated it directly into the hypothalamus circulation (assay generated levels of GnRH directly instead of LH as proxy)
4) = inc. freq. of GnRH pulses ( +LH surge)

22
Q

Mechanisms of feedback - Hypothalamus

A

-GnRH neurones only express ERβ
- BUT Need ERα for +ve feedback (kisspeptin)

-Erα is crucial for reproductive function -Erα knock-out mice

  • absence of ERA receptor = E2 must act on other afferents that project onto GnRH neurones

E2 indirectly stimulates GnRH neurones via other neuronal
inputs:
»Kisspeptin
»Other hypothalamic neurotransmitters e.g.GABAnergic neurons

Science of Repro (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions