Differential Regulation of Luteinizing Hormone-Releasing Hormone and Galanin Messenger Ribonucleic Acid Levels by Alpha1Adrenergic Agents in the Ovariectomized Rat

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Abstract
α(1) -Adrenergic control of luteinizing hormone-releasing hormone (LHRH) and galanin mRNA levels was examined in ovariectomized rats. Each rat was ovariectomized and a permanent bilateral cannula was implanted 1 mm dorsal to the preoptic area. Eleven to 14 days later, each rat received one of three treatments: prazosin (α(1) antagonist, n = 8), methoxamine (α(1) agonist, n = 5) or control (no drug, n = 7). Each drug was suspended in a polyacrylamide gel matrix and delivered to the preoptic area via the bilateral cannula. After 24 h of continuous exposure to the adrenergic agents (or control), rats were anesthetized, decapitated and brains were stored in liquid nitrogen until sectioned (7 μm) on a cryostat. In situ hybridization was performed using a [(32) P]-end-labelled 59mer complementary to LHRH mRNA. Reduced silver grains, proportional to LHRH mRNA content, were quantified for number of LHRH cells per section, number of grains per labelled cell and total number of grains in labelled cells. Compared to the controls, prazosin caused a 32% decrease (P<0.05) in the number of cells expressing the LHRH gene. The LHRH cells from untreated animals had a median of 53 grains/cell with a smooth distribution above and below the median. Treatment with prazosin reduced the median number of grains/cell to 36 (P<0.05). When the number of grains in labelled cells were totalled, prazosin decreased (P<0.01) the number of grains by 47%. Surprisingly, methoxamine caused no quantitative changes in any of the parameters examined. This might be explained if LHRH transcription in control animals was proceeding at near-maximal rates supported, in part, by an endogenous α(1) ligand. Alternatively, continuous exposure to this agonist may have resulted in desensitization to its stimulatory effects. When anatomically matched brain tissue sections from these animals were examined for galanin mRNA, no differences among experimental groups were detected. In conclusion, administration of an α(1) -adrenergic antagonist into the preoptic area suppressed levels of LHRH mRNA but not galanin mRNA. Therefore, the data suggest that an endogenous α(1) ligand, such as norepinephrine (or epinephrine), is required to maintain a high level of LHRH gene expression in the ovariectomized rat.