Neuron-specific SOCS3 knock-out prevents HCD-induced suppression of the estradiol-induced LH surge in female mice. A, Serum LH concentration at the time of surge occurrence (left bars), percentage of mice exhibiting an LH surges (serum concentration >2 ng/ml) (middle bars), and percentage of activated GnRH neurons (i.e., coexpressing cFos) (right bars) after 120 d of HCD feeding (n = 5 or 6 per group). B, Representative example of GnRH neurons (brown unenhanced DAB cytosolic staining) that are either negative or positive (indicated by arrowhead) for cFos immunoreactivity (black nickel-enhanced DAB nuclear staining). Control and SOCS3 knock-out mice were fed an HCD from weaning for 110 d (sufficient to induce infertility in controls but not knock-outs). They were then ovariectomized and subjected to an estradiol-induced preovulatory surge induction model. C, When the ability of this estradiol to induce an LH surge was tested after 225 d of HCD feeding, both control and SOCS3 KO mice exhibited low plasma LH concentrations (n = 7–10 per group). Scale bar, 20 μm. *p < 0.05 versus controls.