HPG Axis Flashcards
HPG Axis diagram
Hypothalamus to Pituitary
structures
General Kisspeptin (KISS1/Kiss1) role
what was it also known as?
metastin
role: gatekeeper of puberty
Controls synthesis and secretion of GnRH in GnRH neurons
Upstream of GnRH
GNRH neurones are expressed in which two regions?
- Arcuate Nucleus
- Medial preoptic nucleus
GNRH that is synthesised and secreted move through the what?
to get to the anterior pituitary
The hypophyseal portal system
Where is Kisspeptin expressed?
Two spots in something*
In the hypothalamus:
- Arcuate Nucleus (ARC)
- Anterventral Periventricular Nucleus (AVPV)
Kisspeptin receptor (GPR54/KISS1R)
Where is it expressed?
Expressed on GnRH neurons.
Inactivating mutations of KISS1R and Kisspeptin = ?
failure to undergo spontaneous puberty.
Activating KISS1R mutations = ?
Can lead to precocious puberty
Kisspepetin neurons and GnRH neurons diagram interaction
Kisspeptin neurons send projections to GnRH neurons, and binding to KISS1R expressed on GnRH neurons.
A bolus of Kisspeptin correlates with a…
peak of LH secretion
GnRH is secreted in pulses from hypothalamus every…
30-120min
Slow frequency GnRH pulse favours..
FSHb transcription and FSH release,
Rapid GnrH pulse frequency favours..
LHb transcription and LH release
Continuous pulsatile release results in..
cessation of response
What is generating the GnRH pulse ?
A sub-population of Arcuate Nucleus Kisspeptin Neurons (ARNKISS)
Studies showed:
ARNKISS were all found to exhibit intermittent periods of synchronized electrical activity which had a near perfect correlation with pulsatile LH secretion.
Inhibition of ARNKISS in the mid-caudal region of the arcuate nucleus suppressed pulsatile LH secretion
Gonadotrophin hormones: LH, FSH (and hCG)
Features and structure as themselves
- Glycoprotein hormones
- Heterodimeric
- Pulsatile (due to B units)
Follicle-stimulating hormone (via FSHR) function:
Testis?
Regulation of Sertoli cell metabolism
Follicle-stimulating hormone (via FSHR) function:
Testis?
Regulation of Sertoli cell metabolism
Follicle-stimulating hormone (via FSHR) function:
Ovary?
- follicular maturation
- granulosa cell estrogen synthesis
Luteinising-stimulating hormone (via LHR) function:
Testis?
Stimulation of Leydig cell androgen synthesis
Luteinising-stimulating hormone (via LHR) function:
Ovary?
- theca cell androgen synthesis
- ovulation
- progesterone production of corpus luteum
General function of gonadotrophins
Supports germ cell growth, development and maturation
to produce..
oocyte and sperm, competent for fertilisation
Leydig cells?
LHR or FSH expression and why is this then crucial?
LHR expression
->
Androstenedione, DHEA, Testosterone production
Sertoli cells?
LHR or FSH expression and why is this then crucial?
FSHR expression
->
Sertoli cell metabolism (important for spematogenesis)
+ Testosterone –> dihydrotestosterone
Theca cells?
LHR or FSH expression and why is this then crucial?
LHR expression
—>
Testosterone and Androstenedione
Granulosa cells?
LHR or FSH expression and why is this then crucial?
FSHR expression –> through aromatase takes Testosterone and Androstenedione and forms Oestradiol and Oestrone
Corpus luteum?
LHR or FSH expression and why is this then crucial?
LHR (and FSHR) expression
—>
Progesterone (and oestrogens)
Inhibin
Features and structure as themselves
Peptide hormones
Heterodimers
2 isoforms of inhibin: A and B.
Inhibin role
inhibits FSH secretion via direct negative feedback to anterior pituitary
In males which inhibin is invovled?
Inhibin B
In females which inhibin is invovled?
Inhibin expression is cyclical depending on the phase of the menstrual cycle.
Can switch from inhibin B in the follicular phase to Inhibin A in the luteal phase.
Summary of HPG axis in depth
