N-(2,4-dinitrophenyl)-5-methoxytryptamine, a novel melatonin antagonist: effects on sexual maturation of the male and female rat and on oestrous cycles of the female rat [corrected].
N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] has recently been synthesized and shown to antagonize the inhibitory effect of melatonin on the release of dopamine in vitro from the hypothalamus of female rats. In the present study the ability of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] to inhibit in vivo the following melatonin-mediated effects was investigated: (1) delayed sexual maturation of young male rats, (2) delayed sexual maturation of young female rats, (3) inhibition of ovulation in mature female rats and (4) re-establishment of oestrous cycles in adult female rats maintained in continuous light. The inhibitory effect of daily melatonin injections, given in the afternoon, on the growth of the prostate gland and seminal vesicles and on serum testosterone concentrations in young male rats was prevented by daily injections of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected]. Daily injections of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] alone did not affect sexual maturation of young rats. In young male rats treated through the drinking water with melatonin, the growth of the accessory sex organs, but not that of the testes, was delayed and serum concentrations of testosterone were lower than in untreated rats. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water increased serum concentrations of testosterone but did not significantly affect the weights of the accessory sex organs. Simultaneous administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] and melatonin through the drinking water prevented completely, in a dose-dependent manner, the melatonin-mediated decrease in epididymal weights and in serum concentrations of testosterone and partially inhibited the delayed growth of the prostate glands and seminal vesicles. In young female rats treated with melatonin through the drinking water for 30 days, the growth of the ovaries was inhibited and serum concentrations of oestradiol were lower than in untreated rats. The growth of the uterus was not significantly affected. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water did not significantly affect uterine and ovarian weights or oestradiol concentrations. Simultaneous administration of melatonin and N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water prevented completely the melatonin-mediated decrease in ovarian weights and in serum oestradiol concentrations. Ovulation during presumptive oestrus was prevented in adult female rats treated through the drinking water for 7 days with melatonin. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] alone did not significantly affect the average numbers of ova shed and corpora lutea present. Simultaneous administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] and melatonin prevented completely the melatonin-mediated inhibition of ovulation; the average number of ova shed was the same as in controls.(ABSTRACT TRUNCATED AT 400 WORDS)
Laudon
M
M
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Israel.
Yaron
Z
Z
Zisapel
N
N
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D004971:Estrus / Q000187:drug effects*; D005260:Female; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects; D051381:Rats; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives*; D012741:Sexual Maturation / Q000187:drug effects*; D014363:Tryptamines / Q000494:pharmacology*
D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter; D014363:Tryptamines; C059440:N-(2,4-dinitrophenyl)-5-methoxytryptamine; D012701:Serotonin; D008735:5-Methoxytryptamine; D008550:Melatonin