A subpopulation of gonadotropin-releasing hormone neurons in the adult mouse forebrain is γ-Aminobutyric acidergic.

Gonadotropin-releasing hormone (GnRH) neurons play a pivotal role in reproductive function. GnRH is released in distinct pulses that are regulated by neurotransmitters or neuromodulators. With immunohistochemistry and GAD67-GFP knockin mice, this study shows for the first time that a subset of GnRH neurons in the forebrain of adult mouse is γ-aminobutyric acid (GABA)-ergic. There is a gender difference in the percentage of GnRH neurons expressing GAD67-GFP in female vs. male mice. The percentage of GnRH neurons expressing GAD67-GFP decreased after castration of female mice and increased to the normal female level after estradiol treatment. The percentage of GnRH neurons expressing GAD67-GFP did not change significantly in intact, castrated, or castration + testosterone propionate-treated male mice. During the female estrous cycle, the percentage of GnRH neurons expressing GAD67-GFP was higher during the estrous stage than during the diestrous stage. During sexual maturation of postnatal development, GnRH neurons did not express GAD67-GFP until postnatal day (P) 15, and the gender differences were first detected at P30, which corresponds to the maturation stage. In conclusion, our data suggest that 1) a subset of GnRH neurons in mouse forebrain is GABA-ergic, 2) expression of GAD67-GFP in GnRH neurons is at least in part regulated by estrogen, and 3) GnRH neurons secrete GABA to regulate themselves.