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Alcohol Alters Luteinizing Hormone Secretion in Immature Female Rhesus Monkeys by a Hypothalamic Action

Oregon National Primate Research Center (G.A.D., S.R.O.), Oregon Health and Science University, Beaverton, Oregon 97006-3448; and Department of Integrative Biosciences (R.K.D., H.M.S., W.L.D.), College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4458

Address all correspondence and requests for reprints to: W. Les Dees, Ph.D., Department of Integrative Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4458. E-mail: ldees{at}cvm.tamu.edu.

We determined whether the effect of alcohol (ALC) to suppress LH secretion in immature female monkeys is due to a hypothalamic or pituitary site of action. Beginning at 20 months of age, four monkeys received a single intragastric dose of ALC (2.4 g/kg), and four monkeys received an equal volume of a saline/sucrose solution daily until they were 36 months old. For the hypothalamic response test, two basal samples (3.5 ml) were collected at 15-min intervals via the saphenous vein, and then N-methyl-D-L-aspartic acid (NMA; 20 mg/kg) was given iv and four more blood samples collected. Three weeks later, this protocol was repeated except LH-releasing hormone (LHRH) (5 µg/kg) was used to test pituitary responsiveness. NMA or LHRH was administered 3 h after the ALC. After the pituitary challenge, each monkey was ovariectomized and 6 wk later, implanted with an indwelling subclavian vein catheter. Blood samples were drawn every 10 min for 8 h to assess effects of ALC on post-ovariectomy LH levels and the profile of LH pulsatile secretion. The hypothalamic challenge showed NMA stimulated LH release in control monkeys, an action that was blocked by ALC. The pituitary challenge revealed that LHRH stimulated LH release equally well in control and ALC-treated monkeys. A post-ovariectomy rise in LH was observed in both groups, but levels were 45% lower in ALC-treated monkeys. This reduction was attributed to an ALC-induced suppression of both baseline and amplitude of pulses. Results demonstrate that the ALC-induced suppression of LH in immature female rhesus monkeys is due to an inhibitory action of the drug at the hypothalamic level.