The coordinated activity and secretions of the hypothalamic-pituitary-gonadal axis are vital to male reproduction. Activation of a small, diffuse population of neurons in the preoptic/hypothalamic area result in the pulsatile secretion of gonadotropin-releasing hormone (GnRH) into the hypophysial-portal vasculature which stimulates luteinizing hormone and follicle-stimulating hormone from the pituitary, driving testosterone secretion and spermatogenesis, respectively. Testosterone exerts feedback inhibition at both the levels of the pituitary and hypothalamus. The precise preoptic/hypothalamic target site and underlying mechanisms that govern the negative feedback actions of testosterone are unknown. The possibility exists that testosterone may act directly on the GnRH neuron, itself or through a pre-synaptic GABAergic mechanism. The general hypothesis is that in males, testosterone exerts its negative feedback action on luteinizing hormone secretion by reducing GnRH neuronal activity either directly and/or through a GABA-mediated pre-synaptic mechanism. This proposal utilizes the GnRH-green fluorescent protein transgenic mouse model in combination with visualized cell-attached and whole-cell patch clamp recordings and single-cell RT PCR techniques to test this hypothesis.
Specific Aim 1 will determine whether testosterone directly alters the active membrane properties and firing pattern of GnRH neurons.
Specific Aim 2 will determine if testosterone alters GABAergic synaptic transmission on GnRH neurons.
Specific Aim 3 will determine if testosterone alters androgen receptor, GnRH and GABAA receptor subunit mRNA levels in identified GnRH neurons

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HD008733-03
Application #
6636777
Study Section
Reproductive Biology Study Section (REB)
Program Officer
De Paolo, Louis V
Project Start
2002-03-01
Project End
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
3
Fiscal Year
2003
Total Cost
$49,864
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523