# Effects of development and prenatal androgen exposure on GnRH neuron intrinsic properties

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $39,969

## Abstract

Project Summary
Gonadotropin-releasing hormone (GnRH) neurons form the final central pathway for the control of reproductive
function, releasing GnRH in a pulsatile manner. Low frequency GnRH pulses favor the secretion of follicle-
stimulating hormone (FSH), whereas high frequency GnRH pulses favor the secretion of luteinizing hormone
(LH). Disruptions to the secretory patterns of these hormones can result in subfertility or infertility. Polycystic
ovary syndrome (PCOS), and in particular hyperandrogenemic PCOS, is a disorder in which disruptions to
these hormone release patterns result in impaired fertility. Specifically, sustained high frequency LH, and
presumably GnRH, pulses are a hallmark of hyperandrogenemic PCOS. To study neuroendocrine aspects that
may contribute to this disorder, the proposed work uses a prenatally androgenized (PNA) mouse model. PNA
mice recapitulate many neuroendocrine phenotypes reported in women with hyperandrogenemic PCOS,
including disrupted reproductive cycles, elevated LH-pulse frequency and increased testosterone. Studies of
GFP-identified GnRH neurons from three-week-old PNA females revealed that action potential firing activity is
lower than in cells from controls. In contrast, GnRH neuron activity is increased in cells from adult PNA mice
relative to controls. This was a curious observation as GABAergic transmission, which is excitatory in GnRH
neurons, was increased at both of these developmental timepoints. In 3-wk old PNA females, GnRH neurons
have a reduced firing response to local GABA application compared to controls, but there is no change in
either reversal potential for current through the GABAA receptor or in the basal membrane potential of these
cells. Together these observations suggest the postulate that changes occur in voltage-gated channels of
GnRH neurons from PNA mice to compensate for increased excitatory synaptic input in young mice but that
these changes are not maintained in adults, leading to hyperactivity. My early data indicate that GnRH neuron
excitability and action potential characteristics can be similar among the groups, but have different underlying
ionic conductance characteristics as a result of development and PNA treatment. The first aim of this project
tests how voltage-gated potassium (K+) currents, which play a large role in how neurons respond to synaptic
inputs and generate action potentials, are altered among these groups. Our findings we be used to generate
computational models of potassium currents that will assist in this interpretation The second aim will use
dynamic clamp to test if GnRH neurons from control vs PNA mice respond differently to representative trains of
simulated GABA conductances from our previous work and/or current injection. We will also test how modelled
potassium currents interact with the native milieu of recorded GnRH neurons to account for differences in
response. Completion of this project will provide insight into the intrinsic properties ...

## Key facts

- **NIH application ID:** 10534568
- **Project number:** 1F31HD110279-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jennifer Jaime
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,969
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10534568

## Citation

> US National Institutes of Health, RePORTER application 10534568, Effects of development and prenatal androgen exposure on GnRH neuron intrinsic properties (1F31HD110279-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10534568. Licensed CC0.

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