Date of Graduation
A seasonal change in GnRH secretion is well documented in sheep. An alteration in the estradiol (E2) negative feedback mechanism is thought to promote ovarian quiescence via GnRH inhibition during spring and summer months in response to changes in day length. It is evident that the hypothalamus becomes hypersensitive to E2 during this time, but the mechanism driving the shift is not completely understood. However, it is clear that A15 dopaminergic (DA) neurons in the retrochiasmatic area (RCh) play a key role in these seasonal changes. These neurons mediated E2 negative feedback in anestrus, but do not respond to E2 in the breeding season. Since these neurons do not contain ERÎ± the first experiment tested the role of ERÎ² by comparing the effects of E2 and genistein microimplanted into the RCh. E2 microimplants inhibit LH pulse frequency in ovariectomized (OVX) anestrus, but not breeding season, ewes. E2 does not act via ERÎ² since genistein microimplants were ineffective in this area. Injection of a DA D2 receptor antagonist overcame the inhibitory effect of local E2 microimplants, further demonstrating the DA neurons in this area are influenced by E2. Based on these results and preliminary tract tracing data, we postulated that an interneuron mediates E2 negative feedback. We next tested the possible roles of NO and GABA as neurotransmitters of these interneurons by examining the effects of NOS inhibitors and ligands to GABAA and GABAB receptors in the A15 area. The NOS inhibitors had no effects, suggesting that NO is not involved. In contrast, GABAA agonist increased LH secretion suggesting a possible role for a GABAA postsynaptic receptor. The results of the GABAB ligands were more difficult to interpret because both an antagonist and an agonist increased LH secretion. This could reflect methodological differences or the presence of both pre- and postsynaptic GABAB receptors. Finally, the mediation of E 2 negative feedback by a GABAergic influence is further supported by the presence of GAD67-IR positive close contacts on TH-IR A15 neurons. Together, these data provide support for a GABA/DA mechanism that modulates the seasonal suppression of GnRH.
Hardy, Steven L., "The role of retrochiasmatic neurons in seasonal breeding in the ewe." (2003). Graduate Theses, Dissertations, and Problem Reports. 8994.