Hypothalamic Pituitary Gonadal Axis: 1 Flashcards
Why do we need the HPG Axis?
We need the HPA Axis in order to reproduce
How do we get reproduction?
- Correct process of sex determination (genotypic sex) and differentiation (phenotypic sex).
- Sexual maturation- Puberty
- Production and storage of enough supply of eggs & sperm.
- Correct number of chromosomes in egg and sperm
- Actual sexual intercourse! Egg & sperm have to be transported and meet
- Fertilisation, implantation, embryonic and placental development
- Once delivered, to nurture individual until capable of “independent” life
What controls gonadal function?
Gonadal function is controlled via feedback by:
• Hypothalamic & pituitary peptide hormones.
• Gonadal steroid (and peptide) hormones.
What hormones are released from the hypothalamus?
• Hypothalamus (RH)- Gonadotrophin Releasing Hormone (GnRH), (kisspeptin)
What hormones are released from the pituitary gland?
• Pituitary (SH)- Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH)
What hormone is released from the gonads?
• Gonad- (F) Oestradiol (E2), Progesterone (P4), (M) Testosterone, (Inhibin and activin).
Give an overview of the HPA axis
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Always negative in males, only positive in females during ovulation.
Needed for gamete production.
Kisspeptin acts upstream of GnRH.
Label the Hypothalamic-hypophyseal portal system
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How are LH and FSH released from the anterior pituitary?
- Kisspeptin neurones secrete kisspeptin. This causes GnRH neurones to produce GnRH.
- This then passes through a network of blood vessels till the anterior pituitary to produce FSH and LH which make there way to the circulation
When we’re talking about the hypothalamus, we’re talking about specialised neurons within the brain that secrete hormones. The hypothalamus is composed of various nuclei that not only coordinate reproduction but other functions as well such as spermiogenesis, regulation of appetite etc. In terms of reproduction we’re talking about GnRH and Kisspeptin which are localised there.
Where are the kisspeptin neurones expressed?
- ARC = Arcuate Nucleus
2. AVPV = Anteroventral Periventricular Nucleus
Describe the binding of kisspeptin to cause the release of GnRH
• Kisspeptin neurons send projections to GnRH neurons, and binding to GPR54 expressed on GnRH neurons
How is kisspeptin synthesised?
What kisspeptin-54 used for?
What is Kisspeptin-10 used for?
- Kisspeptin is initially synthesised as a preproprotein. It then undergoes proteolytic cleavage t kisspeptin 54
- This undergoes further cleavage to form other forms.
Kisspeptin-54 - for in vivo clinical studies - can cross the blood-brain barrier
Kisspeptin - 10 - used in cell culture studies, cheaper to produce a 10 amino acid protein, it has a high biological activity
Where is GnRH synthesised?
How and where is it secreted?
• Synthesised and secreted from GnRH neurons
- Secreted in a pulsatile fashion-pulse generator orchestrated
- Hypothalamic expression- ARC and MPN (Parvocellular system)
- ARC = Arcuate Nucleus
- MPN = Medial preoptic nucleus
What does GnRH bind to?
• 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 is GnRH synthesised?
- GnRH is initially synthesised as a preproprotein before it undergoes proteolytic cleavage
- GAP has similar functions to GnRH