The long term goal of this proposal is to elucidate the neuroendocrine mechanisms responsible for reproductive dysfunction in aging female rats at the systemic, cellular and molecular levels. It remains to be determined whether chronic exposure to preovulatory estradiol (E2) levels causes loss of the LH surge-inducing actions of E2 that occur in aging rats, and if so by what mechanism. This proposal will focus on the role of estrogen receptors (ER) in the medullary noradrenergic neurons that project to the hypothalamic luteinizing hormone-releasing hormone (LHRH) neurons in mediating the loss of the positive feedback action of E2.
The specific aims are to test the hypothesis that chronic exposure of ovariectomized (OVX) rats to preovulatory levels of E2: (1) causes a sequential loss of the LH surge-inducing actions of E2 and P; (2) suppresses the gene expression of estrogen receptor (ER) in the NE neurons that project near the LHRH perikarya; (3) decreases the number and/or proportion of ER immunopositive NE neurons; and (4) alters the in vivo pattern of NE release. The proposed studies will determine the effect of E2 on changes in plasma LH concentrations by radioimmunoassay, dialysate NE levels by high pressure liquid chromatography, ER-alpha and -beta m/RNA levels by in situ hybridization, and immunocytochemical localization of ER-alpha and -beta in noradrenergic neurons. The results of these studies should increase our understanding of the mechanisms whereby E2, which plays an important role in mental health, alters brain function.
| Legan, S J; Tsai, H-W (2003) Oestrogen receptor-alpha and -beta immunoreactivity in gonadotropin-releasing hormone neurones after ovariectomy and chronic exposure to oestradiol. J Neuroendocrinol 15:1164-70 |
| Tsai, Houng-Wei; Legan, Sandra J (2002) Loss of luteinizing hormone surges induced by chronic estradiol is associated with decreased activation of gonadotropin-releasing hormone neurons. Biol Reprod 66:1104-10 |
| Tsai, H W; Legan, S J (2001) Chronic elevation of estradiol in young ovariectomized rats causes aging-like loss of steroid-induced luteinizing hormone surges. Biol Reprod 64:684-8 |
