Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus controls pituitary gonadotropin secretion in male and female rats. The majority of GnRH neurons located in the medial preoptic area (MPO) of both male and female rats are not sex-specific in number and distribution, and cellular features. Thus, neural network regulating GnRH neuron plays a key role in the sexual dimorphism of gonadotropin release. A luteinizing hormone (LH) surge triggering ovulation occurs in female animals but not in male animals suggesting that sexually dimorphic effects of estrogen may underlie the sexual difference in GnRH-LH release. Estrogen signals to GnRH neurons may mediate via estrogen- sensitive afferents because GnRH neurons do not appear to express the estrogen receptor (ER), which is crucial for feedback control. The GnRH neurons express specific subunits of the gamma-aminobutyric acid (GABA) receptors and in vivo microdialysis studies have indicated that remarkable sex differences occur in GABA release in the MPO in intact and gonadectomized estrogen-primed rats. In the MPO, most GnRH neurons are known under the influence of GABA, and GABAergic neurons express ERα. These observations provide evidence that GABA is a potent regulator of the GnRH neurons. Even under the same estrogen environment, estrogen regulates GABA release in a sexually dimorphic manner suggesting that neural network of hypothalamus contributes to sexual dimorphism of GABA release which in turns leads to sexual dimorphism of gonadotropin release in male and female rats. In this review, we propose a possible neural mechanism in the MPO underlying sex-specific and time-dependent GABA and gonadotropin release.