The hypothalamic insulin-like growth factor-1 receptor and its relationship to gonadotropin-releasing hormones...

Reproduction in vertebrates is controlled by hypophysiotropic gonadotropin-releasing hormone (GnRH) neurones. Pulsatile GnRH release increases during reproductive development, resulting in the onset and progression of puberty and, ultimately, the acquisition and maintenance of adult reproductive function. These changes in GnRH release are largely due to inputs to GnRH cells from other factors, including the neurotrophic factor, insulin-like growth factor-1 (IGF-1). Here, molecular studies were undertaken to quantify expression of IGF-1 receptor (IGF-1R) mRNA in the preoptic area-anterior hypothalamus (POA-AH) and mediobasal hypothalamus (MBH)-median eminence (ME), the sites of GnRH perikarya and neuroterminals, respectively. Immunocytochemical studies were also carried out to study the anatomical relationship between the IGF-1R and GnRH neurones. Experiments were performed in a developmental context using neonatal (P5), peripubertal ( approximately P30) and adult (P60) male and female mice. We found that IGF-1R mRNA levels in the POA-AH were significantly different among all age groups, with levels higher at P60 then P5 or approximately P30. Levels of IGF-1R mRNA in the MBH-ME were lower at P5 than approximately P30 or P60. Qualitative observations suggested that IGF-1R immunoreactivity in POA-AH increased from P5 through P60. Quantitative double-label immunocytochemistry studies showed that GnRH perikarya expressed IGF-1R. Taken together, the results demonstrate expression of, and developmental changes in, IGF-1R gene and protein in brain regions containing GnRH and other neuroendocrine cells. Moreover, the novel finding that the IGF-1R is expressed on GnRH perikarya in vivo suggests a potential direct anatomical locus where IGF-1 can regulate reproductive development and function.