Role of the central ascending noradrenergic system in the regulation of luteinizing hormone responsiveness to testosterone negative feedback in the adult male rat.
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.
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*
D002395:Catecholamines; D006892:Hydroxydopamines; D013739:Testosterone; D016627:Oxidopamine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D009638:Norepinephrine