Interactive Roles of Gonadotropin-Releasing Hormone and RF-Amide Related Peptide 3 in Adenohypophyseal Physiology and Reporduction in the Mare
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The seasonal termination of ovarian cycles in mares initiated near the time of the autumnal equinox is a significant managerial issue for horse breeders world-wide. Studies presented herein had two over-arching aims. In Aim I, objectives were to develop the principals needed to apply gonadotropin-releasing hormone (GnRH) therapeutics for routinely establishing pregnancies in the winter anovulatory mare. We first tested the hypothesis that continuous administration of native GnRH, beginning in either early February or March, would induce ovulation without reversion to an anovulatory state following treatment withdrawal. Continuous 28-d treatments elevated circulating luteinizing hormone (LH) and stimulated spontaneous ovulation much earlier than controls. However, mares treated only in February ceased ovarian cycles at termination of treatment. In contrast, mares administered GnRH in March continued to exhibit estrous cycles. Thus, we concluded that GnRH treatment must continue through March to ensure continued escape from winter anovulation. We then tested the hypothesis that the Julian day of conception could be accelerated in winter anovulatory mares treated continuously with native GnRH for 56 d beginning on February 1. Indeed, GnRH treatment caused a marked increase in the frequency of pregnancy compared to controls. Data illustrated that continuous administration of native GnRH is a practical and highly efficient option for managing seasonal anovulation. In Aim II, we examined hypothalamic distribution, adenohyphyseal receptor gene expression, and ligand functionality of RFRP3 in the mare during the breeding and non-breeding seasons. Hypothalamic RFRP3 mRNA was detected in the mare; however, neither hypothalamic expression of RFRP3 nor its anterior pituitary receptor differed between reproductive states. We then used equine adenohypophyseal cell culture to test the hypothesis that RFRP3 reduces the responsiveness of the equine gonadotrope to GnRH. Addition of RFRP3 to cell culture failed to counter the effects of GnRH. Finally, the effects of a RFRP3 receptor-signaling antagonist (RF9) were examined in winter anovulatory mares. A robust increase in circulating concentrations of LH relative to controls was observed in response to RF9 treatments, but treatments had no effect on adenohypophyseal responsiveness to GnRH. Data provide indirect evidence that antagonism of the RFRP3 system by RF9 may be at the GnRH neuronal level.
Thorson, Jennifer Frances (2013). Interactive Roles of Gonadotropin-Releasing Hormone and RF-Amide Related Peptide 3 in Adenohypophyseal Physiology and Reporduction in the Mare. Doctoral dissertation, Texas A&M University. Available electronically from