Does nitric oxide act in the ventromedial preoptic area to mediate oestrogen negative feedback in the seasonally anoestrous ewe?

Abstract

Seasonal anoestrus in the ewe results from enhanced oestrogen negative feedback. Recent data have implicated the ventromedial preoptic area (vmPOA) as an important site of oestrogen action. This study addressed whether NO acts within the vmPOA to inhibit LH during seasonal anoestrus. In Experiment 1, microimplants containing Nu-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor), S-methyl thiocitrulline (SMTC, neural NOS (nNOS) inhibitor) or empty implants (control) were administered during mid-anoestrus to the vmPOA. L-NAME, but not SMTC, significantly increased LH pulse frequency. For Experiment 2, ewes in late anoestrus were administered 7-nitroindazole (7NI; nNOS inhibitor), L-NAME, SMTC, or empty implants. 7NI, but not L-NAME or SMTC, increased LH pulse frequency. In Experiment 3, the effects of microimplants and microinjections of L-NAME were compared in mid-anoestrus. Microinjections of L-NAME (300 nl at 10 mg/ml) increased LH pulse frequency, but microimplants did not. In late anoestrus, similar microinjections were ineffective. Taken together, the results of Experiments 1-3 suggested that NO inhibition may be stronger during the middle than at the end of seasonal anoestrus. To test this hypothesis, ewes in Experiment 4 received microinjection of L-NAME or vehicle thrice during the non-breeding season; none of the treatments increased LH pulse frequency. These results indicate that NO plays a role in the vmPOA in suppressing LH secretion during seasonal anoestrus because NOS inhibitors were consistently stimulatory when LH pulse frequency was low. However, the inconsistent and modest effects of these inhibitors suggest that NO actions in this area cannot completely account for the effects of inhibitory photoperiod. Reproduction (2007) 134 137-145

Kisspeptin-GPR54 Signaling in Mouse NO-Synthesizing Neurons Participates in the Hypothalamic Control of Ovulation

“…These results are in agreement with data collected from ewes that suggest a role for nitric oxide in the preoptic region in the suppression of GnRH/LH secretion during estrogen-mediated negative feedback in seasonal anoestrus (Stefanovic et al, 2000;McManus et al, 2007), but stand out from those of a previous study performed in rats, in which the pharmacological inhibition of nNOS failed to alter basal or kisspeptin-evoked LH release (Navarro et al, 2005). However, sex differences may account for this discrepancy, as the Navarro study was performed using males, and a recent human study has demonstrated that kisspeptin-stimulated LH release is sexually dimorphic (Jayasena et al, 2011).…”

The Role of KNDy Neurons and Neuronal Nitric Oxide Synthase in the Control of Reproduction in Female Sheep and Nonhuman Primates

“…In OVX ewes, injection of a NOS inhibitor into the third ventricle also decreases mean LH concentrations and LH pulsatility (258). During anestrus, NOS inhibitors administered in the POA have mostly modest and inconsistent effects on LH secretion with some inhibitors increasing LH secretion while others have no effect (259). However, NOS inhibitors never decreased LH secretion, indicating NO most likely acts as an inhibitor of LH secretion in anestrous ewes.…”