6-Methoxybenzoxazolinone (6-MBOA) is a compound originally isolated from naturally growing plants which stimulates reproduction in all mammals so far tested. 6-MBOA causes gonadol hypertrophy in both sexes of the microtine rodent Microtus montanus (vertebrates) with a commensurate increase in reproductive efforts. 6-MBOA administration overcomes the suppressive effects that photoperiods have on M. montanus, and appears to be more important than photoperiods in cueing reproductive behavior. 6-MBOA is now well established as a reproductive stimulant and fertility enhancer; however, there is no information on its mechanism of action at the endocrine or biochemical level. Our initial studies show that 6-MBOA is a melatonin antagonist in that it competitively displaces 3H-melatonin which is specifically bound to protein receptors. Melatonin influences sexual development in humans and other animals and is likely a biological factor influencing psychological depression. Research described in this proposal is intended as the initial phase of a comprehensive study to define effects of 6-MBOA on the neuroendocrine system and its mechanism(s) of action at the cellular and biochemical level. The objectives of the project described here are to: (1) determine primary and secondary target tissues for 6-MBOA by measuring tissue distributions and in vitro binding, (2) measure changes in the gonadotropins LH and FSH by radioimmunoassay after 6-MBOA administration, (3) determine effects of 6-MBOA on the levels of some serum steroids, and (4) study possible 6-MBOA and melatonin-mediated biochemical changes in established target tissues. Methodologies to be used are well established and objective. Results are certain to determine effects of 6-MBOA on the neuroendocrine system.
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