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The GnRH-II system is thought to regulate sexual behaviour through an action in the brain, and/or control gonadotrophin secretion in association with the classical GnRH-I system at the level of the gonadotroph. The aim of this study described in this thesis was to comprehensively investigate the GnRH-II receptor system in a well characterised sheep model. Four types of studies were performed. The first study sequenced the ovine GnRH-II receptor gene by long-distance PCR. The second study investigated GnRH-II receptor gene expression in ovine tissues. The third study investigated evidence for GnRH-II receptor on gonadotrophs. A fourth study used two selective GnRH-I receptor antagonists to test whether administered GnRH-II acts through the GnRH-I receptor to elicit gonadotrophin secretion. In conclusion the presence of a premature stop codon in the ovine GnRH-II receptor, and a major deletion mean it is unlikely that a full 7 transmembrane domain G-protein coupled receptor is expressed in the sheep. RNA transcripts for part of the receptor were detected in testis, ovary and hindbrain, indicating that a partial GnRH-II receptor protein may be produced in a tissue-specific manner. The lack of a Pit-1 binding site in the 5’ flanking sequence of the ovine GnRH-II gene, the lack of RNA transcripts specifically in gonadotrophs and the in vivo evidence collectively suggest that GnRH-II does not function to regulate gonadotrophin secretion in the sheep. Overall these data complement recent published data for the marmoset, African green monkey, rhesus macaque and man, and are consistent with the generalised hypothesis that there has been redundancy in the multiple GnRH receptor systems during vertebrate evolution. |
