Neuropeptide Y (NPY) Delays the Oestrogen‐Induced Luteinizing Hormone (LH) Surge in the Ovariectomized Ewe: Further Evidence That NPY has a Predominant Negative Effect on LH Secretion in the Ewe

Abstract

Studies in rats suggest that neuropeptide Y (NPY) plays a stimulatory role in the generation of the preovulatory luteinizing hormone (LH) surge, via the Y1 receptor. We have investigated this issue using the oestradiol benzoate (EB)-treated ovariectomized (OVX) ewe which is a model for the preovulatory LH surge. A Y1 receptor antagonist (BIBO3304) was infused (25 microg/h) into the third cerebral ventricle (III-V) from 2 h before EB injection for 24 h, and had no effect on the ensuing LH surge. Using in situ hybridization, we then examined expression of NPY mRNA in the arcuate nucleus during the luteal, follicular and oestrous phases of the oestrous cycle, and found that levels were greatest during the luteal phase. Thus, reduced NPY synthesis might be an integral factor in the events leading to the cyclic preovulatory LH surge. This was tested by infusion of NPY (25 microg/h) into the III-V (as above). The NPY infusion delayed the LH surge until the infusion was ceased. High levels of NPY expression during the luteal phase of the oestrous cycle may be caused by progesterone. Thus, we determined whether NPY cells possess progesterone receptors (PR) and whether progesterone treatment up-regulates NPY mRNA expression in the arcuate nucleus. Immunohistochemistry for NPY and PR was performed in OVX, oestrogen-treated ewes, but no NPY cells of the arcuate nucleus were seen to colocalize PR. In situ hybridization for NPY was performed in OVX and OVX ewes treated with progesterone. There was no significant effect of progesterone treatment on NPY mRNA expression in the arcuate nucleus. We conclude that chronically elevated levels of NPY block the preovulatory surge of gonadotropin-releasing hormone/LH secretion in sheep, but high levels of NPY mRNA expression in the luteal phase of the oestrous cycle cannot be explained by an action of progesterone.

Perinatal exposure of female rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces central precocious puberty in the offspring

“…Other studies showed that TCDD distributed at the CNS exerts neurotoxicological effects: a high TCDD dose (10 mg/kg) administered to rats was shown to reduce LH secretion and the number of ova at ovulation (Petroff et al 2001). Exposure to TCDD at 15 mg/kg was reported to decrease the neuropeptide Y level in the arcuate nucleus (Fetissov et al 2004) that is presumably involved in ovulation (Estrada et al 2003) and the sexual maturation of the hypothalamus (Kalra & Kalra 2004). We reported in our previous study ) that the in utero and lactational exposure of rat dams to TCDD resulted in the alteration of the N-methyl-D-aspartate (NMDA) receptor subunit mRNA expression in the brain of their offspring.…”

Estrogen Facilitates both Phosphatidylinositol 3-Kinase/Akt and ERK1/2 Mitogen-Activated Protein Kinase Membrane Signaling Required for Long-Term Neuropeptide Y Transcriptional Regulation in Clonal, Immortalized Neurons

“…Neuropeptide Y (NPY) neurons are implicated in feeding behavior, energy use, and reproductive function (Xu et al, 2000). Because estrogen receptors are present on NPY neurons in vivo (Estrada et al, 2003), and in vitro (Belsham et al, 2004;Titolo et al, 2006), the feedback effects of estrogen on gonadotropin-releasing hormone (GnRH) neurons may be mediated via the NPY neuronal framework. Evidence also indicates that estrogen may play a role in the regulation of NPY synthesis (Shimizu et al, 1996;Ainslie et al, 2001;Pelletier et al, 2007).…”

Genomics of estradiol-3-sulfate action in the ovine fetal hypothalamus

“…Our data suggest that E 2 S treatment might stimulate alterations in appetite and/or energy balance in fetal sheep; however, the mechanism by which this might occur is unclear. Estrogen receptors are present on AGRP and NPY neurons in vivo (17) and in vitro (3,39,40) and can have a dual effect on NPY induction in the adult female. During proestrus, E 2 stimulates NPY expression and release, which in turn contribute to the stimulation of preovulatory GnRH secretion into the hypophysial portal vessels (17).…”

“…Estrogen receptors are present on AGRP and NPY neurons in vivo (17) and in vitro (3,39,40) and can have a dual effect on NPY induction in the adult female. During proestrus, E 2 stimulates NPY expression and release, which in turn contribute to the stimulation of preovulatory GnRH secretion into the hypophysial portal vessels (17). Despite this stimulatory action in these pathways, chronic administration of E 2 has predominately anorectic properties (6,48) in rats and monkeys that depend on the inhibition of NPY and AGRP expression and release (6,14).…”