Test of ML23 as an antagonist to the effects of melatonin in the ram

Abstract

Summary. In Exp. 1, four groups of 8 yearling Soay rams were housed under long days (16L:8D) to induce reproductive quiescence and were treated daily for 12 weeks with: (I) vehicle (2 or 4 ml 50% ethanol/water), (II) ML23 (2 mg), (III) melatonin (2 mg) and (IV) melatonin and ML23 (2 mg of each). All treatments were given orally in the mid-light phase. In the rams receiving melatonin (Group III) there was an earlier increase in the plasma concentrations of FSH and testosterone and regrowth of the testes compared to the controls (time to maximum testicular diameter: 10\m=.\0 \ m=+-\ 0\m=.\5and 15\m=.\3\m=+-\1\m=.\2 weeks). These differences were reversed after the end of the 12-week treatments when rapid testicular regression occurred in melatonin-treated rams but not in the controls. In the group receiving ML23 and melatonin (Group IV), there was early reactivation and regression of the reproductive axis as in the melatonin group (testis max. 9\m=.\9\ m=+-\ 0\ m=. \ 7 and 10\m=.\0\ m=+-\ 0\ m=. \ 5weeks) while in the group receiving ML23 alone (Group II) there was a slower redevelopment and regression as in the controls (testis max. 15\m=.\7\m=+-\1\m=.\1and 15\m=.\3\m=+-\1\m=.\2 weeks). The comparison between the 4 groups in the changes in the blood concentrations of prolactin, voluntary food intake and total body weight also indicated that the treatment with ML23 failed to modify the effect of melatonin (combined treatment vs melatonin) or the effect of the long day photoperiod (ML23 vs vehicle).In Exp. 2, a more soluble derivative of ML23 (called ML23-lysine) was tested in two groups of 4 adult Soay rams which were housed under long days (16L:8D) and treated daily for 12 weeks, as above with: (I) melatonin (2 mg) and (II) melatonin (2 mg) and ML23-lysine (4 mg). In both groups there was a similar reactivation and regression of the testes with no significant differences between the two treatments.The overall results illustrate that the treatments with melatonin in this protocol were effective at influencing a wide range of reproductive and non-reproductive measures in the ram, but that ML23 was unable to antagonize these biological effects of melatonin.

Testicular function and semen characteristics of Awassi rams treated with melatonin out of the breeding season

“…It has also been demonstrated that melatonin increases the mean testosterone concentration (Kennaway and Gilmore, 1985;Lincoln and Ebling, 1985;Lincoln and Kelly, 1989;Bourla, 1991;Chemineau et al, 1992). Melatonin treatment increases ram effect, which may synchronise the oestrus of dams and lead to a more expressed oestrous behaviour, eventually resulting in better reproductive results (Rosa et al, 2000).…”

Failure of Prazosin to Mimic the Effects of Melatonin Under In Vivo and In Vitro Conditions

“…In fact, synthesis of several compounds possessing melatonin antagonist or agonist activity was already reported [Flaugh et al, 1979;Vakkuri et al, 1984;Laudon et al, 1987;Dubocovich, 19871. The biological effects of these analogues were tested under different experimental paradigms [Richardson et al, 1983;Vaughan et al, 1986;Dubocovich, 1987;Weaver et al, 19881, leading, in some cases, to controversial results in different species [ Laudon et al, 1987;Zizapel and Laudon, 1987;Lincoln and Kelly, 1989;Pevet et al, 19891. Some of the putative analogues were also tested for their capacity to displace labelled melatonin from its receptor and were found differing to a great extent in their potency in diverse species [Dubocovich and Takahashi, 1987;Duncan et al, 1988;Stankov et al, 1989 Prazosin, a selective alpha-1 adrenoceptor antagonist was reported to be a potent displacer of the high-affinity component of 2-[ 125I]iodomelatonin binding in hamster brain [Niles et al, 19871 but possessed low or no potency in a transplantable neoplasm [Stankov et at., 19891, rabbit, horse, and sheep brain membranes [Stankov et al, 1990b1, rat median eminence membranes [Stankov, unpublished] and rat suprachiasmatic nuclei [ Laitinen and Saavedra, 19901. Therefore, we report here results obtained under in vivo and in vitro experimental conditions aimed at determining whether the biological effects of melatonin can be duplicated or antagonized by prazosin.…”

“…In fact, synthesis of several compounds possessing melatonin antagonist or agonist activity was already reported [Flaugh et al, 1979;Vakkuri et al, 1984;Laudon et al, 1987;Dubocovich, 19871. The biological effects of these analogues were tested under different experimental paradigms [Richardson et al, 1983;Vaughan et al, 1986;Dubocovich, 1987;Weaver et al, 19881, leading, in some cases, to controversial results in different species Zizapel and Laudon, 1987;Lincoln and Kelly, 1989;Pevet et al,…”