Abstract
The relationship which exists between nutrition and reproduction is well established but poorly understood. Recent studies suggest that the gut peptide, GLP-1, may have a stimulatory effect on the hypothalamic-pituitary-gonadal axis, increasing secretion of GnRH and/or pituitary gonadotrophs (Arbabi, Li, Henry, & Clarke, 2021; Farkas et al., 2016; Outeirino-Iglesias, Romani-Perez, Gonzalez-Matias, Vigo, & Mallo, 2015; C. Vastagh, Farkas, Scott, & Liposits, 2021). However, whether GLP-1 in systemic circulation can increase gonadotroph secretion is unknown, with contradictory results from a study in rats which found that although GLP-1 seemed to stimulate the reproductive axis, administration of the GLP-1 receptor agonist, Exendin-4, had some inhibitory effects (Outeirino-Iglesias et al., 2015)
A preliminary study confirmed proof-of-concept, with intravenous infusion of 2mg of Exendin-4 via indwelling jugular catheter over a one-hour period increasing the secretion of luteinising hormone (LH) in a population of ewes. Oestrus synchronization was used to allow observation of whether this effect differed between the luteal or follicular phase of the oestrous cycle. The effect of Exendin-4 infusion on LH secretion was markedly more pronounced in the follicular phase.
A larger study was then designed using solely ewes in the follicular phase and confirmed the effect of Exendin-4 infusion on LH secretion at a dose of 0.5mg or 2mg. Although Exendin-4 infusion increased LH pulse amplitude, there was no observable effect on inter-pulse interval. Measurement of plasma insulin and glucose concentrations confirmed these dosages were not associated with an incretin effect. There was no observed effect of Exendin-4 infusion on timing of the preovulatory LH surge.
Data from the preliminary study suggested that Exendin-4 also stimulated follicle stimulating hormone (FSH) secretion, however the results of the main experiment suggest we observed an endogenous increase and that Exendin-4 infusion does not have an immediate effect on FSH secretion.
Glucagon-like peptide 1 is produced by post-translational processing of the preproglucagon gene. Preproglucagon gene (GCG) expression has not previously been reported in the sheep. We confirmed that GCG is expressed in the ovine intestine using tissue samples collected from seven sites of the gastrointestinal tract of five ewes. Quantitative PCR was utilized to assess differences in gene expression between sites. Expression increased aborally, being greatest in the rectum and lowest in the forestomachs. This distribution similar to GCG expression in cattle. This suggests the distribution of intestinal L-cells in ruminants is similar to that of monogastric species.
We can conclude that GLP-1 in systemic circulation, such as that produced by the hind-gut, acts to increase LH secretion in the ewe. These findings are consistent with the hypothesis that GLP-1 has a stimulatory effect on the hypothalamic-pituitary-gonadal axis.
A preliminary study confirmed proof-of-concept, with intravenous infusion of 2mg of Exendin-4 via indwelling jugular catheter over a one-hour period increasing the secretion of luteinising hormone (LH) in a population of ewes. Oestrus synchronization was used to allow observation of whether this effect differed between the luteal or follicular phase of the oestrous cycle. The effect of Exendin-4 infusion on LH secretion was markedly more pronounced in the follicular phase.
A larger study was then designed using solely ewes in the follicular phase and confirmed the effect of Exendin-4 infusion on LH secretion at a dose of 0.5mg or 2mg. Although Exendin-4 infusion increased LH pulse amplitude, there was no observable effect on inter-pulse interval. Measurement of plasma insulin and glucose concentrations confirmed these dosages were not associated with an incretin effect. There was no observed effect of Exendin-4 infusion on timing of the preovulatory LH surge.
Data from the preliminary study suggested that Exendin-4 also stimulated follicle stimulating hormone (FSH) secretion, however the results of the main experiment suggest we observed an endogenous increase and that Exendin-4 infusion does not have an immediate effect on FSH secretion.
Glucagon-like peptide 1 is produced by post-translational processing of the preproglucagon gene. Preproglucagon gene (GCG) expression has not previously been reported in the sheep. We confirmed that GCG is expressed in the ovine intestine using tissue samples collected from seven sites of the gastrointestinal tract of five ewes. Quantitative PCR was utilized to assess differences in gene expression between sites. Expression increased aborally, being greatest in the rectum and lowest in the forestomachs. This distribution similar to GCG expression in cattle. This suggests the distribution of intestinal L-cells in ruminants is similar to that of monogastric species.
We can conclude that GLP-1 in systemic circulation, such as that produced by the hind-gut, acts to increase LH secretion in the ewe. These findings are consistent with the hypothesis that GLP-1 has a stimulatory effect on the hypothalamic-pituitary-gonadal axis.
| Original language | English |
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| Qualification | Doctor of Veterinary Studies |
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| Place of Publication | Australia |
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| Publication status | Published - 2024 |