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Physiology 2 > Reproduction: Hypothalamic/Pituitary/Gonadal Axis I > Flashcards

Reproduction: Hypothalamic/Pituitary/Gonadal Axis I Flashcards

1
Q

What are some of the things that the HPG axis is responsible for/needed for?

A
  • Correct process of sex determination sexual and differentiation
  • Sexual maturation - Puberty
  • Production and storage of sufficient supply of eggs & sperm
  • Produce correct number of chromosomes in egg and sperm
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2
Q

In the HPG axis what hormones are secreted by the hypothalamus?

A
  • Gonadotrophin releasing hormone (GnRH)
  • Kisspeptin (newly discovered)
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3
Q

In the HPG axis what hormones are released by the anterior pituitary?

A
  • Follicle stimulating hormone (FSH)
  • Luteinising hormone (LH)
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4
Q

In the HPG axis what hormones are secreted by the gonads?

A
  • Ovaries - Oestradiol (E2), Progesterone (P4)
  • Testes - Testosterone
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5
Q

Breifly explain how the HPG axis works

A
  • Hypothalamus releases GnRH which binds to the GnRH receptor on the anterior pituitary
  • This causes the Gonadtroph cells of the anterior pituitary to produce and then secrete LH and FSH
  • LH and FSH then bind to their receptors on the gonads
  • This causes the gonads to release Oestrogens, Progesterone and Androgens, e.g. testosterone.
  • These hormones then bind to either the hypothalamus or anterior pituitary resulting in negative feedback
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6
Q

What is the one instance in which a hormone released by the gonads leads to positive feedback rather than negative feedback?

A

During ovulation in females Oestrogen is able to produce positive feedback by causing a surge in LH production by the anterior pituitary

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7
Q

Describe how the Hypothalamic-hypophyseal portal system transports GnRH from the hypothalamus to the anterior pituitary

A
  • GnRH is produced and then released by GnRH neurons in the hypothalamus
  • The GnRH then travels from those GnRH neurons to the primary capillary plexus of the hypophyseal portal system
  • GnRH travels in the circulation from the primary capillary plexus to the secondary capillary plexus
  • Once in the secondary capillary plexus GnRH is able to bind to the GnRH receptors on the anterior pituitary
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8
Q

What is the role of kisspeptin within the HPG axis?

A

Kisspeptin stimulates the release of GnRH form GnRH neurons in the hypothalamus

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9
Q

How does Kisspeptin stimulate GnRH release from the GnRH neurons?

A
  • Kisspeptin neurons send signals to GnRH neurons
  • This reults in the kisspeptin neurons releasing kisspeptin which then binds to kisspeptin receptor (KISS1) on the GnRH neurons
  • This results in the activation of the GnRH neurons which eventually leads to the secrtetion of GnRH
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10
Q

In what regions of the hypothalamus is Kisspeptin expressed?

A
  • Arcuate Nucleus (ARC)
  • Anteroventral Periventricular Nucleus (AVPV)
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11
Q

Originally kisspeptin is synthesised as prepro-kisspeptin that then undergoes proteolytic cleavage to form Kissppetin. Explain this protelytic cleavage process

A
  • Prepro-kisspeptin is cleaved between amino acid 68 and amino acid 121 to form Kisspeptin-54
  • Kisspeptin-54 can be further processed to form Kisspeptin-14; Kisspeptin-13 or Kisspeptin-10.
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12
Q

In what region/s of the hypothalamus are the GnRH neurons located?

A
  • Located mainly in Arcuate nucleus (ARC)
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13
Q

GnRH is also synthesised as a prepro-protein. Explain the catalytic cleaving process for GnRH

A
  • Prepro-GnRH is cleaved to form GnRH which is a decapeptide (10 amino acid peptide)
  • Associated with GnRH is a protein called GAP (GnRH-associated protein)
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14
Q

In what way is GnRH released from the GnRH neurons in the hypothalamus?

A

GnRH is released in a pulsate manner every 30-120 minutes

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15
Q

How does the frequency of pulsatile secretion of GnRH affect LH and FSH secretion?

A
  • Pulsatile GnRH release from hypothalamus stimulates a pulse of LH and FSH secretion from the anterior pituitary
  • A slow frequency pulse of GnRH favours FSH secretion
  • A rapid frequency pulse of GnRH favours LH secretion
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16
Q

Why is the pulsatile release of GnRH important?

A
  • If GnRH is released continuously it will eventually lead to the cessation of the secretion of FSH and LH from the anterior pituitary
  • This is because continous release results in the saturation of the GnRH receptors (GnRHR) on the anterior pituitary which results in gonadatroph cells to stop producing LH and FSH
  • Pulsatile relase of GnRH also important because it helps to induce the LH surge from anterior pituitary during ovulation
17
Q

What are the 2 types of GnRH that are used in therapeutics?

A
  • Synthetic GnRH - same structure as endogenous GnRH
  • GnRH analogues - modified GnRH (can be an agonist or an antagonist)
18
Q

What modifications are done to GnRH to produce GnRH analogues?

A
  • Modified so that GnRH analogues have a much longer half-life than normal GnRH
  • Also modified so GnRH analogues have much greater receptor affinity
19
Q

What is the difference in the way synthetic GnRH and GnRH analogus are administered? What is the reason for this difference

A
  • Syntheric GnRH administered in pulses
  • GnRH analogues administered in a single bolus
  • This is because GnRH analogues have a much higher receptor affinity than synthetic GnRH so not as much needs to be administered to have the same effect
20
Q

Both agonist and antagonist GnRH analogues result in the inhibition of GnRH release from the hypothalamus. How do both types of GnRH analogue do this?

A
  • Agonist GnRH analogue binds to GnRH receptor on gonadtroph cells
  • This causes them to synthesise and secrete LH and FSH
  • Because of the longer half-life the agonist GnRH analouge stays bound to the GnRH receptor
  • This eventually causes the receptor to become uncoupled from the rest of the G protein signalling pathway
  • This leads to the receptor becoming unresponsive to GnRH
  • Antagonist GnRH bins to GnRH receptor on gonadatroph cells
  • This binding blocks the GnRH recptor preventing any downstream effects from happening
21
Q

What are some clinical uses of Synthetic GnRH and GnRH analogues?

A
  • Ovulation induction and IVF
  • Control of prostate cancer
  • Control of ovarian and endometrial cancers
  • Control of breast cancer in pre-menopausal women
22
Q

What are some characteristics of the Gonadtrophin hormones LH and FSH?

A
  • Heterodimeric peptides – common α-subunit and hormone-specific β-subunit
  • Contain N-linked carbohydrate side chains which are required for biological function
  • α and β-subunits need to be together to produce biological effects
  • α-subunits are synthesized in excess while β-subunit synthesis dependent on GnRH secretion
23
Q

How is β-subunit synthesis of the Gonadotrophin hormones dependent on GnRH secretion?

A
  • Slow pulsatile release of GnRH results in the synthesis of the FSH β-subunit so FSH is synthesised
  • Rapid pulsatile release of GnRH results in synthesis of the LH β-subunit so LH is produced
24
Q

Is the pulsatile release of FSH and LH important for their biological activity?

A
  • No pulsatile release of LH and FSH not important for biological activity
  • This is in contrast to pulsatile release of GnRH which is VERY important for its biological activity
25
Q

What are the functions of LH in both the testis and the ovaries?

A
  • Testis - LH stimulates androgen synthesis, e.g. testosterone, in the Leydig cells
  • Ovaries - Theca cell androgen synthesis
    • Ovulation
    • Causes remodelling of ovulated follicle into corpus luteum
26
Q

What are the functions of FSH in both the testis and ovaries?

A
  • Testis - Regulation of spermatogenesis in the sertoli cells as well as regulation of sertoli cell metabolism
  • Ovaries - Follicular maturation
    • Induces Granulosa cell oestrogen synthesis
27
Q

In the ovaries what happens to the androgens produced by Theca cells?

A
  • Androgens (mainly testosterone) produced by Theca cells travel to the Granulosa cells
  • In the Granulosa cells the Androgens are then converted in Oestrogens via the enzyme Aromatase
28
Q

In the testis what happens to the Androgens (testosterone) produced by the Leydig cells?

A
  • Androgens produced by the Leydig cells travel to the Sertoli cells
  • Once in the Sertoli cells the Androgens get converted into Oestrogens via the Aromatatse enzyme

Physiology 2 (29 decks)

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