# An Investigation of the Effects of Formononetin on Hypothalamic Gonadotropin-releasing Hormone, Kisspeptin and Tachykinin 2 Gene Expression in Rats: Formononetin Affects Gnrh, Kiss1 and Tac2

## TL;DR

This study shows that formononetin, a phytoestrogen, affects genes in the rat hypothalamus linked to reproductive hormone regulation.

## Contribution

The study reveals formononetin's impact on Gnrh, Kiss1, and Tac2 gene expression in the hypothalamus of rats.

## Key findings

- 40 µg formononetin significantly reduced Gnrh and Tac2 mRNA levels compared to the control.
- Both 20 and 40 µg formononetin significantly decreased Kiss1 mRNA levels.
- Formononetin may regulate the reproductive axis by downregulating GnRH-related signaling pathways.

## Abstract

Red clover and its main derivative, formononetin, belong to the
phytoestrogens. They are clinically used to alleviate mood disorders, anxiety,
and hot flashes. Formononetin may interfere with the reproductive axis due to
its estrogenic potency and its ability to bind estrogen receptors. To find some
molecular mechanisms mediating the effects of formononetin on the
hypothalamus-pituitary-gonadal (HPG) axis, this research aimed to investigate
the effects of formononetin on the hypothalamic mRNA levels of
gonadotropin-releasing hormone (Gnrh), kisspeptin1(Kiss1) and tachykinin 2
(Tac2).

Fifteen male Wistar rats weighing 200±10 g were
divided into three groups (n=5). Group 1 as the control group, received saline.
Groups 2 and 3 received 20 and 40 µg of formononetin via the third cerebral
ventricle. The hypothalamic samples were dissected. The Gnrh, Kiss1 and Tac2
gene expression was measured by real-time PCR.

Injection of 20 µg
formononetin did not significantly decrease the mRNA levels of Gnrh and Tac2
compared to the control group. However, injection of 40 µg formononetin
significantly reduced the mRNA levels of Gnrh and Tac2 compared to the control
group. Injection of 20 and 40 µg formononetin, significantly declined the mRNA
levels of Kiss1 compared to the control group.

Present results
indicated that formononetin may be involved in the regulation of the
reproductive axis via reducing the activity of hypothalamic GnRH neurons and
downregulation of the kisspeptin and neurokinin B signaling pathways upstream of GnRH neurons.