Brainscape's Knowledge GenomeTM

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


See full index

Physiology 2: Sem 3 > REPRO: Hypothalamic/Pituitary/Gonadal Axis I > Flashcards

REPRO: Hypothalamic/Pituitary/Gonadal Axis I Flashcards

1
Q

HPG axis

A

Hypothalamus-pituitary-gonad axis, the negative feedback loop that regulates sex-hormone production.

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

Practically, what do we need to reproduce?

A
  • correct process of sex determination (genotypic sex) and differentiation (phenotypic sex)
  • sexual maturation (puberty)
  • production and storage of sufficient supply of eggs and sperm
  • sexual intercourse, where the egg and sperm have to be transported and meet
  • fertilisation, implantation, then embryonic and placental development
  • once delivered, we need to nurture the individual until it is capable of ‘independent’ life
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

The HPG axis is known as the master controller of reproduction.

How does it control it?

A

Gonadal function is controlled by feedback by:

  • the hypothalamic and pituitary peptide hormones
  • the gonadal steroid (and peptide) hormones

The hypothalamus releases hormones that positively affect the pituitary, which then releases hormones that positively affect the gonads. The gonads then release hormones that, mostly negatively, affect the hypothalamus and pituitary. Thus, their function is controlled.

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

What are the hormones of the HPG axis?

A

HYPOTHALAMUS (RH):

  • gonadotrophin-releasing hormones (GnRH)
  • kisspeptin

PITUITARY (SH):

  • follicle-stimulating hormone (FSH)
  • luteinising hormone (LH)

GONADS:

  • [F] oestradiol (E2)
  • [F] progesterone (P4)
  • [M] testosterone
  • inhibin
  • activin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Steps of HPG Axis

A
  • Hypothalamus releases GnRH to the pituitary
  • FSH and LH produced in the anterior pituitary
  • FSH and LH act on gonads
  • Steroid hormones synthesized (oestrogen, progesterone, androgens)
  • Steroid hormones exhibit negative feedback on the pituitary and hypothalamus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe kisspeptin.

A
  • it’s expressed in two different nuclei in the hypothalamus - ARC and AVPV
  • acts upstream of GnRH neurones (ie. it regulates GnRH production) [paracrine regulation]
  • facilitates the release of GnRH, increasing gonadotrophin secretion by anterior pituitary
    • the kisspeptin neurons send projections to GnRH neurons, and bind to GPR54 expressed on GnRH neurons
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where is kisspeptin expressed?

A

it’s expressed in two different nuclei in the hypothalamus:

  • Arcuate nucleus (AN)
  • Anteroventral periventricular nucleus (APVN)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Kisspeptin synthesized as?

A

preproprotein

-undergoes cleavage into active forms

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

Kisspeptin in research

A

Kp-54 is used in clinical research because it crosses the blood-brain barrier

Kp-10 can’t cross barriers and so used in in vitro cell culture studies (cheaper to make 10 amino acid protein than 54 amino acid protein)

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

Describe GnRH.

A
  • it’s synthesised and secreted from parvocellular neurones in the hypothalamus
  • it’s secreted in a pulsatile fashion - orchestrated by pulse generators (a special set of neurons)
  • it binds to the GnRH receptor (GnRHR) on gonadotroph cells of the anterior pituitary to stimulate the synthesis and secretion of gonadotrophin hormones - LH and FSH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is GnRH synthesized as?

A

preproprotein

  • undergoes further cleavage into a decapeptide
  • secreted along with GAP protein (GnRH associated protein)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Expand on the importance of pulsatility with LH and FSH release.

A
  • a GnRH pulse of the hypothalamus stimulates a pulse of LH and FSH secretion from the pituitary
  • slow frequency pulses favour FSH release, while rapid frequency pulses favour LH release [this occurs via differential pathway activation]
  • continuous release -shuts down HPG axis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Explain the therapeutic exploitation of GnRH.

A
  • SYNTHETIC GNRH - has the same structure as endogenous GnRH
    • its pulsatile administration is stimulatory (for fertility)
  • used in those with pubertal delay or failed to undergo puberty; or those with mutations in GnRH production/secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q 
GnRH Analogues (agonists + antagonists) 
How are they administered and what are they used for?
A
  • single bolus administration

- used in inhibitory fashion (i.e. shuts down HPG axis for IVF stimulation and hormone-dependent cancer treatments)

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

Describe the mechanism of action of synthetic GnRH and GnRH analogues, as agonists.

A

WITH AGONISTS:

  1. It binds to the receptor, GnRHR
  2. It activates the signaling pathway
  3. It stimulates gonadotrophin synthesis and secretion
  4. There is then the uncoupling of GnRHR from G-protein signaling
  5. GnRHR is now non-responsive to GnRH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the mechanism of action of GnRH analogues, as antagonists.

A

WITH ANTAGONISTS:

  1. It binds to the receptor, GnRHR
  2. It blocks the receptor
  3. There are no downstream effects
17
Q

List some clinical uses of GnRH analogues.

A
  • ovulation induction and IVF
  • prostate cancer
  • GnRHR/GnRH and ovarian and endometrial cancers
  • ER+ breast cancer in pre-menopausal women
  • endometriosis
  • uterine fibroids
  • PCOS
18
Q

Describe the structure of gonadotrophin hormones.

A

Heterodimeric peptides containing:

  • alpha subunit
  • hormone specific beta subunit (gives gonadotrophins their unique hormonal properties)
  • they are glycoprotein hormones, so the N-linked carbohydrate side chains are required for biological function [free subunits have no biological action], if gonadotrophin is de-glycosylated, it would cease to be active
  • α subunits are synthesised in excess with the β limiting the hormone concentration
  • pulsatile secretion is due to pulsatile GnRH release from the hypothalamus, but the pulsatile secretion is not necessary for biological activity
19
Q

How are alpha and beta subunits of gonadotrophins synthesized?

How are the gonadotrophins released?

A

Alpha subunits synthesized in excess via constitutive secretion

Bets subunits synthesized in a limited fashion because it is GnRH dependent:

  • slow GnRH pulse causes FSHβ expression
  • fast GnRH pulse causes LHβ expression

in a pulsatile fashion (due to pulsatile release of GnRH)

20
Q

What are the functions of LH in the gonads?

A

In the testis:
- stimulation of Leydig cell androgen synthesis

In the ovary:

  • stimulates theca cells for androgen synthesis
  • stimulates corpus luteum for progesterone synthesis
  • ovulation
21
Q

What are the functions of FSH in the gonads?

A

Testis: stimulates Sertoli cells which convert androgens to oestrogens and also regulate spermatogenesis

Ovaries: stimulates granulosa cells for oestrogen synthesis (hence follicular maturation)

Physiology 2: Sem 3 (39 decks)

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