# Neural and pituitary mechanisms linking epilepsy to co-morbid reproductive endocrine dysfunction

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $390,230

## Abstract

PROJECT SUMMARY
Both men and women with temporal lobe epilepsy (TLE), the most common partial epilepsy in adults, exhibit
higher rates of reproductive endocrine disorders compared to the general population. Reproductive endocrine
disorders significantly impact quality of life and, if untreated, can result in elevated risks for other central
nervous system, metabolic, and cardiovascular disorders, and cancer. Seizures appear to be major drivers of
reproductive endocrine co-morbidities, but the neural mechanisms underlying this relationship have not been
described. In the proposed work, we will elucidate neural mechanisms that link epilepsy to reproductive
endocrine dysfunction. Hypothalamic gonadotropin-releasing hormone (GnRH) neurons form the final common
pathway in the brain's control of reproduction and thus likely play critical roles in the pathophysiology of
epilepsy-associated reproductive endocrine disorders. Proper GnRH release patterns are necessary to drive
pulsatile luteinizing hormone (LH) release from the pituitary gland in both males and females. Clinical studies
have reported disrupted patterns of LH release in men and women with epilepsy, but the mechanistic
underpinnings have yet to be elucidated. A major gap in knowledge thus exists about the effects of epilepsy on
GnRH neurons, their synaptic afferents, and downstream impacts on pituitary function. Our overall objectives
in the proposed studies are to determine key functional changes in hypothalamic-pituitary cells and circuits in a
mouse model of TLE. We recently reported that female estrous cyclicity is disrupted in most epileptic female
mice in this model, indicating that it is appropriate for these studies. Our central hypothesis is that seizure
activity drives changes in the activity of GnRH neurons and their synaptic inputs, thereby impacting
downstream pituitary LH release. We will test this hypothesis using an innovative combination of patch clamp
electrophysiology, electroencephalography (EEG), optogenetics, pituitary gene expression analysis, and a
cutting-edge ultrasensitive assay for determining mouse LH release patterns in vivo. In Aim 1 we will perform
the first direct investigations of epilepsy-associated changes in GnRH neuron firing activity, intrinsic excitability,
and fast synaptic inputs. In Aim 2 we will determine the functional relationships between hippocampal seizure
activity, hypothalamic GnRH release, and pituitary response to GnRH. Successful completion of these Aims
will have positive translational impact and further the goals of the NINDS Epilepsy Research Benchmarks by
providing key mechanistic insights into the underlying neural and pituitary substrates of reproductive endocrine
disorders that commonly arise with epilepsy.

## Key facts

- **NIH application ID:** 10128512
- **Project number:** 5R01NS105825-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Catherine A Christian-Hinman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,230
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128512

## Citation

> US National Institutes of Health, RePORTER application 10128512, Neural and pituitary mechanisms linking epilepsy to co-morbid reproductive endocrine dysfunction (5R01NS105825-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10128512. Licensed CC0.

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