| Luteinizing hormone (LH) signaling in the gonads and the adrenal glands promotes sex steroid synthesis. LH signaling in the brain has however not been characterized. To examine LH/hCG signaling in the brain, I examined three pathways intimately associated with brain health and dysfunction: (1) neurosteroid production, (2) amyloid-beta precursor protein (AbetaPP) processing and Abeta deposition, and (3) metal ion homeostasis. LH induced neuronal pregnenolone production by modulating LH receptor and steroidogenic acute regulatory (StAR) protein expression, thereby increasing mitochondrial transport and P450scc-mediated cleavage of cholesterol for pregnenolone synthesis and secretion. Neither gonadotropins nor estradiol signaling modulated AbetaPP processing or the production of Abeta in an animal model of amyloidosis, suggesting these sex hormones are not involved in the deposition of Abeta, the major component of amyloid plaques in the Alzheimer's disease brain. Finally, gonadotropins were shown to be negatively correlated with the concentration of copper, but not other metal ions, in the brain. Taken together, our results indicate the presence of functional LH receptors in the brain through which LH may modulate StAR expression, neurosteroid production and metal ion homeostasis. These findings are the first report of a mechanism for regulating neurosteroid production. |
