Gonadotrophin releasing hormone

Gonadotrophin releasing hormone is a 10 amino acid peptide, with N- and C-terminals blocked to enzymatic degradation. It is synthesised as a 92 amino acid pre-prohormone comprising a 23 amino acid signal peptide, the 10 amino acid GnRH sequence, and a 56 amino acid GnRH-associated peptide.

It is secreted by hypothalamic neurons in the arcuate nucleus and the orga-num vasculosum lamina terminalis. The neurons responsible arise as precursor peripheral sensory neurons of the nasal epithelium, from the medial olfactory placode, and migrate into the hypothalamus. Failure of migration of the neurons is associated with Kallman's syndrome of hypogonadotrophic hypogonadism and anosmia. The neurons do not have any axonal connections with other neuronal networks. Their axons are directed into the median eminence, where they are apposed to the hypophyseal portal vessels.

Hypothalamus GnRH

Oestradiol

Progesterone

Testosterone

Pituitary -

LH FSH

Gonads

Inhibin Activin

Figure 10.5 Hypothalamic-pituitary-ovarian pathway. GnRH, gonadotrophin releasing hormone; LH, luteinising hormone; FSH, follicle stimulating hormone.

The neurons have rhythmic intrinsic depolarisation and secretory activity with g self-generated pulsatile secretion, involving short periods of abrupt secretion °

d separated by large periods of low or undetectable secretion. g

Gonadotrophin releasing hormone travels by axonomic flow to the axon g terminals of the median eminence. It binds to anterior pituitary gonadotrophs ■<

g that secrete FSH and LH. The activation mechanism is calcium-dependent |

activation of a specific membrane receptor adenyl cyclase-cyclic AMP process. The GnRH receptor is a member of the seven transmembrane domain G-protein-coupled family of receptors.

The reproductive cycles commence at puberty as a hypothalamic pulse generator is activated and stimulates the GnRH neurons. Gonadotrophin releasing hormone simultaneously regulates FSH and LH secretion. It has a short plasma half-life, of 2-4 minutes due to rapid proteolytic cleavage. Follicle stimulating hormone and LH are glycopeptides consisting of two subunits, alpha and beta. They share the alpha subunit. Specificity resides in the beta subunit.

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