# Dissecting the Role of Tachykinins in the Generation of GnRH Pulses

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $347,727

## Abstract

ABSTRACT
The activation of the gonadotropic axis requires the pulsatile release of the hypothalamic
decapeptide GnRH. Reproduction is thwarted in the absence of these pulses. Despite
this critical feature of GnRH release, the nature of the central mechanisms that govern
this pulsatile release remain unknown. In recent years, Kiss1 neurons of the arcuate
nucleus have been posed as likely candidates to hold this pulse generator through the
coordinated action of its co-transmitters tachykinin neurokinin B (NKB) and dyrorphin A
(Dyn), which has led these neurons to be termed KNDy neurons. I propose a model in
which NKB stimulates and Dyn inhibits kisspeptin release from KNDy neurons leading to
a pulsatile pattern that would then be translated into GnRH, and therefore LH, pulses.
However, we have recently documented that other tachykinins (substance P, SP and
neurokinin A, NKA) can activate KNDy neurons, adding an additional complex layer to
this model. Importantly, recent studies in rodents and monkeys indicate that the action of
tachykinins to induce LH release happens at the level of KNDy neurons and is therefore
kisspeptin-dependent. However, we have recently observed that in the presence of
circulating estradiol (E2) levels, both NKB and SP evoke a potent increase in LH release
in a kisspeptin-independent manner, which compromises the previous model.
Importantly, KNDy neurons and GnRH neurons (albeit to a lesser extend) express the
receptors for SP (Tacr1) and NKB (Tacr3), suggesting that tachykinins may be able to
act at both neuronal levels to induce LH release under the right sex steroid conditions.
The overall goal of this proposal is to characterize the role of each tachykinin in the
frequency and amplitude of LH pulses in the mouse at the KNDy neuron vs GnRH
neuron using a series of complementary functional, neuroanatomical and genetic
studies. The successful completion of this proposal will offer new strategies to treat
reproductive disorders affecting GnRH secretion.

## Key facts

- **NIH application ID:** 9921213
- **Project number:** 5R01HD090151-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Victor Manuel Navarro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,727
- **Award type:** 5
- **Project period:** 2017-07-28 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921213

## Citation

> US National Institutes of Health, RePORTER application 9921213, Dissecting the Role of Tachykinins in the Generation of GnRH Pulses (5R01HD090151-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9921213. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*