Figure 9.

In vivo blockade of TACE activity targeted to the ME of the hypothalamus delays the onset of puberty in female rats, as assessed by the time at first ovulation. A, Ventral view of the hypothalamus illustrating the ME localization of a stainless steel cannula carrying in its tip the TACE inhibitor TAPI-2. B, A schematic representation mapping the anatomical localization of the implants. The blocker (TAPI-2; black circles) or vehicle (DMSO/cocoa butter; white circles) were delivered to the ME within the tip of a stereotaxically implanted stainless steel cannula; some implants were located too caudally (within the mammillary bodies; gray squares) and thus serve as an additional control group. C, The number of rats reaching puberty at a given postnatal age (expressed as percentage of the total number of animals per group) is significantly reduced by ME blockade of TACE activity. D, The mean age at first ovulation is also significantly delayed in TAPI-2-implanted rats. Error bars represent the mean ± SEM age at first ovulation. ***p < 0.001 versus control group; n = 6 rats per group). AHA, Anterior hypothalamic area; DMH, dorsomedial hypothalamus; OC, optic chiasm; POA, preoptic area; PVH, paraventricular hypothalamic nucleus; SC, suprachiasmatic nucleus; VMH, ventromedial nucleus.