ABSTRACT

I. Development of Model Cell Lines for the GnRH Neuron ...... 142 II. Transcriptional Regulation of the GnRH Gene ........................ 142

A. The Neuron-Specific Enhancer of the GnRH Gene ............ 143 1. Identification of the GnRH Enhancer ............................. 143 2. The Role of GATA Protein-Binding Elements

in the GnRH Enhancer..................................................... 143 3. The Role of the POU-Homeodomain Transcription

Factor Oct-1 in the GnRH Enhancer ............................... 145 B. The GnRH Promoter ............................................................. 146

1. Identification of Functional GnRH Promoter Elements ............................................................................ 146

2. POU-Homeodomain Proteins and Promoter Function ............................................................................ 146

3. The Role of Otx2 in Promoter Activity .......................... 147 III. Regulation of GnRH by Neurotransmitters, Growth

Factors, and Hormones .............................................................. 147 A. Repression of GnRH Gene Expression by NMDA ............. 147 B. Nuclear Receptor Regulation of GnRH Gene

Expression .............................................................................. 148 C. Activin Regulation of GnRH Gene Expression................... 148

IV. Summary...................................................................................... 148 V. Acknowledgments ...................................................................... 149

References ............................................................................................. 149

As the ultimate regulator of reproductive function, gonadotropin-releasing hormone (GnRH) is situated at the peak of the hypothalamic-pituitarygonadal axis. GnRH neurons integrate information from the CNS and periphery to control reproductive maturation, cycles, and behavior. They are regulated by a variety of neurotransmitters, steroids, and peptide hormones. Studies of hypothalamic ultrastructure using double-staining techniques have indicated that dopamine, neurotensin, substance P, catecholamines, GABA, and estrogen-concentrating neurons, among others, may directly communicate with GnRH neurons.