Student t Test), and Aza treated rats had a greatly diminished LH response to ovariectomy, performed on PND 24 and assessed on PND 28 (C=52.56 ± 6.93 ng ml−1, n=6 vs Aza=7.43 ± 2.76 ng ml−1, n=6; t=6.48, p<0.001, Student t Test). Despite this deficiency, the pituitary response to in vivo administration of GnRH on PND 28 was normal in Aza treated rats (Fig. 2b), indicating the absence of a pituitary defect. To evaluate the ability of GnRH neurons to respond to a physiological neuroendocrine stimulus, medial basal hypothalamic (MBH) fragments from PND 28 rats, which contain the median eminence-arcuate nucleus (ME-ARC) region, were exposed to kisspeptin, a potent GnRH secretagogue 24. The ME-ARC from Aza treated rats responded to kisspeptin with significantly more GnRH release than vehicle-treated controls (Fig. 2c), suggesting cellular hyper-responsiveness presumably due to a deficiency in endogenous kisspeptin production.
