Estradiol and progesterone regulate the expression of insulin-like growth factor-I receptor and insulin-like growth factor binding protein-2 in the hypothalamus of adult female rats

Gonadal hormones interact with in sulin-like growth factor-I (IGF-I) to reg ulate synaptic plasticity during the estrous cycle in the rat mediobasal hy pothalamus. It has been proposed that tanycytes, specialized glial cells li ning the ventral region of the third ventricle, may regulate the availabili ty of IGF-I to hypothalamic neurons. IGF-I levels in tanycytes fluctuate du ring the estrous cycle. Furthermore, estrogen administration to ovariectomi zed rats increases IGF-I levels in tanycytes, while progesterone, injected simultaneously with estrogen, blocks the estrogen-induced increase of IGF-I levels in tanycytes. To test whether hormonal regulation of IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) may be involved in the accumu lation of IGF-I in tanycytes, we assessed the effect of ovarian hormones on the levels of these molecules in the mediobasal hypothalamus of adult fema le rats. Ovariectomized animals were treated with either oil, estrogen, pro gesterone, or estrogen and progesterone simultaneously and then killed 6 or 24 h later. Some neurons, some astrocytes, and many tanycytes in the medio basal hypothalamus were found by confocal microscopy to be immunoreactive f or IGF-IR. IGFBP-2 immunoreactivity was restricted almost exclusively to ta nycytes and ependymal cells and was colocalized with IGF-IR immunoreactivit y in tanycytes. By electron microscope immunocytochemistry using colloidal gold labeling, IGF-IR and IGFBP-2 immunoreactivities mere observed in the m icrovilli of tanycytes in the lumen of the third ventricle. IGF-IR and IGFB P-2 immunoreactive levels on the apical surface of tanycytes were significa ntly decreased by the administration of progesterone, either alone or in th e presence of estradiol. IGF-IR levels in the mediobasal hypothalamus, meas ured by Western blotting, were not significantly affected by the separate a dministration of estradiol or progesterone to ovariectomized rats. However, the simultaneous administration of both hormones resulted in a marked decr ease in IGF-IR protein levels. Estradiol administration to ovariectomized r ats increased IGFBP-2 immunoreactive levels in the hypothalamus. While prog esterone did not significantly affect IGFBP-2 expression, the simultaneous injection of estradiol and progesterone resulted in a marked decrease in IG FEP-2 protein Levels. The effect of estradiol on IGFBP-2 was observed both in protein and mRNA levels, suggesting a transcriptional regulation. Howeve r, the simultaneous administration of progesterone and estradiol had differ ent effects on IGF-IR protein and IGF-IR mRNA levels, as well as on IGFBP-2 protein and IGFBP-2 mRNA levels, suggesting a postranscriptional action. T hese findings indicate that estradiol and progesterone regulate the express ion of IGF-IR and IGFBP-2 in the mediobasal hypothalamus of adult female ra ts. Regulation of the hypothalamic IGF-I system by ovarian hormones may be physiologically relevant for neuroendocrine regulation and for synaptic pla sticity during the estrous cycle. These results do not support the hypothes is that estrogen-induced accumulation of IGF-I by tanycytes is mediated by the hormonal regulation of IGF-IR. However, estrogen-induced up-regulation of IGFBP-2 and progesterone-induced downregulation of IGF-IR and IGFBP-2 le vels in the apical plasma membrane of tanycytes may be involved in the fluc tuation of IGF-I levels in the mediobasal hypothalamus during the estrous c ycle. (C) 2000 John Wiley & Sons, Inc.