Fig. 1.

Schematic of neuroendocrine feedback systems involved in the control of GnRH/LH secretion that are reprogrammed by prenatal T excess. Upper panel: Pattern of secretion of GnRH/LH in control female sheep; lower panel: Pattern of secretion of GnRH/LH in prenatal T-treated female sheep. (1) E₂ negative feedback: GnRH/LH release is under the control of negative feedback action of E₂, which is predominant during the prepubertal and anestrus period. Prenatal T-treatment decreases the sensitivity of the neuroendocrine axis to E₂, resulting in increased LH pulse frequency. (2) E₂ positive feedback: Positive feedback actions of E₂ responsible for generation of the preovulatory GnRH/LH surge and onset of cyclicity. Prenatal T-treated females present delayed and dampened LH surge. (3) P₄ negative feedback: After puberty (right panels), elevated concentrations of P₄ reduce secretion of GnRH/LH pulses preventing ovulation to occur during the luteal phase. Prenatal T-treatment decreases the sensitivity of the neuroendocrine axis to P₄, leading to increased LH pulsatile release. Panels illustrating the hormonal profile in control females have been modified from [46].