title: Role of the central ascending noradrenergic system in the regulation of luteinizing hormone responsiveness to testosterone negative feedback in the adult male rat.
abstract: It is well established that testosterone (T) feeds back on the brain and the anterior pituitary to inhibit gonadotropin secretion. However, the precise mechanism by which T exerts its central inhibitory action is poorly understood. We hypothesized that central noradrenergic activity decreases hypothalamic sensitivity to T negative feedback. To test this hypothesis, we compared the dose-response relationships between T and luteinizing hormone (LH) and between T and follicle-stimulating hormone (FSH) in adult male rats chronically depleted of hypothalamic norepinephrine (NE) to the dose-response curves exhibited by control animals. Depletion of hypothalamic NE was achieved by two independent methods: 1) by bilateral transection of the ascending noradrenergic system at the level of the mesencephalon, and 2) by intracerebroventricular infusion of the neurotoxin, 6-hydroxydopamine. After allowing 2-3 weeks for recovery from this initial surgery, all animals were castrated, and 3 weeks later were outfitted with subcutaneous T-containing or empty (sham) implants for a period of 48 hours. We observed that despite a profound chronic reduction in hypothalamic noradrenergic activity, the dose-response relationship between plasma T and the gonadotropins remained unaltered. These data demonstrate that normal amounts of hypothalamic noradrenergic activity are not essential for T to exert its negative feedback effect on gonadotropin secretion. Furthermore, they suggest that chronic removal of hypothalamic NE does not alter gonadotropin sensitivity to T negative feedback.
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D005246:Feedback; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006892:Hydroxydopamines / Q000633:toxicity; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D002395:Catecholamines; D006892:Hydroxydopamines; D013739:Testosterone; D016627:Oxidopamine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D009638:Norepinephrine