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Physiology - The Reproductive System > 2- HPG Axis I > Flashcards

2- HPG Axis I Flashcards

1
Q

What do we need to reproduce?

A

Correct process of sex determination and differentiation
Sexual maturation - puberty
Production and storage of sufficient supply of eggs and sperm
Correct number of chromosomes in egg and sperm
Actual sexual intercourse - egg and sperm must be transported to meet
Fertilisation
Nurture individual

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2
Q

How does the HPG axis act as the master controller of reproduction?

A

Gonadal function is controlled by feedback by hypothalamic and pituitary peptide hormones and gonadal steroid and peptide hormones

Feedback is always negative in males and also in females expect in ovulation where it’s positive

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3
Q

What are the hormones of the HPG axis?

A

Hypothalamus- gonadotropin releasing hormone (GnRH) /(Kisspeptin)

Pituitary- follicle stimulating hormone (FSH) and luteinising hormone (LH)

Gonad -
Estradiol(E2)/ progesterone(P4) - female
Testosterone - male

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4
Q

Give an overview of the HPG Axis

A

GNRH is released by the hypothalamus and acts on the gonadotropin cells in the anterior pituitary this causes the pituitary to release LH and FDH
This then causes the gonads to produce either oestrogen, progesterone or androgens
Feedback is always negative in males and females with the exception of ovulation

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5
Q

What stimulates the production of GnRH?

A

Kisspeptin neurones produce Kisspeptin and in response GnRH neurones produce GnRH

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6
Q

Where are Kisspeptin neurone’s expressed?

A

In the the hypothalamus
More specific:
ARC and AVPV

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7
Q

Where does Kisspeptin work?

A

They work upstream of GnRH
Kisspeptin neurons send projections to GnRH neurone and binding to GpR54 expressed on GnRH neurones

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8
Q

Where are GnRH neurones expressed?

A

In the hypothalamus
More specific
ARC and MPN ( parvocellular system)

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9
Q

How does GnRH work?

A

It’s binds to GnRH receptors on gonadotropin cells of the anterior pituitary to stimulate the synthesis and secretion of gonadotropin hormones LH and FSH

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10
Q

Explain the importance of pulsatility in GnRH secretion?

A

GnRH is secreted in pulses from the hypothalamus every 30-120 mins

A GnRH pulse stimulates a pulse of LH and FSH secretion from the anterior pituitary

A pulsatile secretion of GnRH secretion is vital for the stimulation of LH and FSH secretion

Slow frequency pulse favours - FSH secretion
Rapid frequency pulse favours - LH secretion

A continuous release of GnRH results in cessation of response in LH and FSH secretion

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11
Q

What are the therapeutic applications of GnRH?

A

Synthetic GnRH- same structure as endogenous GnRH
- admistered in a pulsating manner
- stimulates the HPG axis
- used in correct delayed puberty

GnRH analogues- modified GnRH peptide structures
- administered as a single bolus( continuous delivery)
- long half life
- inhibits the HPG axis
- used in IVF treatments

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12
Q

What is the similarities and differences between the GnRH agonist and antagonist?

A

They both shut down the HPG axis
However an antagonist shuts the HPG axis straight away and an agonist stimulates release of gonadotropins before shutting down the HPG axis

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13
Q

What is the mechanism of synthetic GnRH?

A

Works similar to endogenous GnRH
GnRH binds to the receptor and activates signalling which stimulates gonadotropin synthesis and secretion. Due to the short half life of GnRH dissociation of GnRH from the GnRHR occurs and the GnRHR is responsive to the next GnRH pulse

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14
Q

What is the mechanisms of GnRH analogues (agonists)?

A

Agonists-
Bind to the GnRH receptor and activate signalling, this stimulates the synthesis and secretion for gonadotropin. Due to the long half life of the agonist it desensitised the receptor by the uncoupling of the GnRHR from the G protein signalling, the GnRHRRbis now non responsive to GnRH - hence shutting down the HPG axis

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15
Q

What is the mechanism of GnRH analogues (antagonist)?

A

Antagonist-
It binds to the GnRH receptor and blocks the receptor so there are no downstream effects
Shuts down the HPG axis

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16
Q

What are the clinical uses of GnRH and GnRH analogues?

A

Ovulation induction and IVF
Prostrate cancer
Brest cancer
Pre menopausal women

17
Q

What is the structure of gonadotropin hormones?

A

Hetrodimeric peptides - common alpha subunit and a hormone specific beta subunit

N linked carbohydrates side chain required for biological function

Alpha subunits are synthesised in excess with beta subunits limiting the hormone concentration

Gonadotropin hormones are secreted due to the pulsation release of GnRH from the hypothalamus but pulsatile secretion is not required for their function

18
Q

What subunit is favoured during the different frequencies of pulsating GnRH release?

A

Fast pulsatile release favours the beta subunit of LH

Slow pulsatile release favours the beta subunit of FSH

The alpha subunits are not affected by this

19
Q

What is the function of LH in the testis?

A

Stimulation of leading cell androgen synthesis

20
Q

What is the function of LH in the ovaries?

A

Theca cell androgen synthesis

Ovulation

Progesterone production of corpus leteum

21
Q

What is the function of FSH in the testis?

A

Regulation of sterols cell metabolism

22
Q

What is the function of FSH in ovaries?

A

Follicular maturation

Granulosa cell oestrogen synthesis

23
Q

Where are male gonadal steroids produced?

A

Leydig cells-
Express LHR
Produce androgens such as testosterone

Sterols cells-
Express FSHR
Steroli cell metabolism
Spermatogenesis

24
Q

Where are the female gonadal steroids produced?

A

Theca cells-
Have LHR receptors
Produce androgens

Granulosa cells-
Have FSHR receptors
Androgens are converted to oestrogens by enzyme aromatise which cataclysms the conversion

Corpus luteum-
LHR and FSHR
Production of progesterone and oestrogens

25
Q

What are the functions of oestrogens?

A

Folliculogenesis
Positive feedback triggers ovulation

Example;
- oestrodiol
- oestrone

26
Q

What is the function of androgens?

A

Spermatogenesis

Examples;
- androstenedione
- testosterone
- dihydrotestosterone

27
Q

What is the function of progesterone?

A

Prepares the uterus for implantation
Maintains conditions required for the early stages of pregnancy

28
Q

Give an overview for the female HPG axis?

A

GnRH released by the hypothalamus in pulses in response to Kisspeptin. GnRH acts on gonad cells in the pituitary to release FSH and LH
LH- acts on Theca cells to produce androgens
FSH - acts on granulosa cells to convert androgens into oestrogens

Negative feedback except in ovulation which is positive

29
Q

Give an overview of the male HPG axis?

A

Release of GnRH from the hypothalamus due to Kisspeptin, GnRH acts on cells in the pituitary to release LH and FSH
LH- acts on the leydif cells to produce testosterone
Sertoli cells - convert testosterone into oestrogens

Physiology - The Reproductive System (12 decks)

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