Intracerebroventricular injection of neuropeptide Y suppresses luteinizing hormone pulses in mice.

In vivo animal study investigating the effects of central neuropeptide Y administration on luteinizing hormone secretion and gene expression in mice.

“Therefore, our objective was to determine the in vivo action of central NPY administration on LH pulses in mice.”

Adult male and female C57BL/6J mice, including ovariectomized (OVX) females and gonadectomized (GDX) or gonad-intact males.

“Adult male and female C57BL/6J mice bred from founders purchased from Jackson Laboratory (stock # 000664) aged 3–7 months were housed 2–5 animals per cage under standard laboratory conditions with a 12:12 light/dark photocycle in our vivarium at Colorado State University.”

The final analysis included a total of 57 female mice and 43 male mice across the primary experiments, with additional smaller cohorts for specific mechanistic tests.

“Final analysis included a total of 57 mice (OVX+ Oil: Saline n = 10, NPY n = 16; OVX + E2: Saline n = 17, NPY n = 14).”

Blood sampling periods lasted 90 minutes before and 90 minutes after injection, with tissue collection occurring 1 or 3 hours post-injection.

“Mice were allowed 30 min to recover from anesthesia, then frequent blood sample collection was resumed for another 90 min (Figure 1A).”

Intracerebroventricular injection of NPY suppressed luteinizing hormone pulses in ovariectomized female and gonadectomized male mice.

“Intracerebroventricular injection (ICV) of NPY robustly suppressed LH pulses in ovariectomized (OVX) female and gonadectomized (GDX) male mice.”

NPY administration increased the abundance of mRNA encoding dynorphin in the arcuate nucleus one hour after injection.

“In assessment of KNDy neurons, we found a statistically significant increase in the abundance of mRNA encoding dynorphin in micro‐punches of the arcuate nucleus 1 h after ICV injection of NPY.”

The LH response to exogenous kisspeptin was not altered by NPY pretreatment, suggesting GnRH neurons and gonadotrope cells remained responsive.

“In further support of the hypothesis that NPY impairs KNDy cells, we found that animals pretreated with NPY or saline had the same response to exogenous kisspeptin, suggesting gonadotropin‐releasing hormone neurons and gonadotrope cells remain fully responsive to stimulation.”

The study was complicated by an unexpected suppression of LH secretion in estradiol-replaced mice caused by brief isoflurane exposure and handling, which precluded full analysis of NPY effects in that group.

“Thus, the reduction in mean LH and number of pulses observed following ICV injection was likely caused by handling and isoflurane exposure, precluding analysis of modulation of these features by E2.”