Melatonin and the Influence of the Pineal Gland on Timing of the LH Surge in Rats

Abstract

The purpose of this study was to determine if the temporal relationship between the LH surge and the photo-period is influenced by melatonin and the pineal gland in the rat. The timing of melatonin synthesis and of preovulatory LH release is reciprocally related; and since melatonin blocks LH secretion, it was hypothesized that the pineal ‘hormone’ contributes normally to termination of the LH surge. To test this hypothesis, we examined the temporal pattern of phasic LH secretion after altering pineal activity in rats with regular estrous cycles. Termination of the LH surge was delayed in rats exposed to a photophase acutely prolonged into the night of proestrus; a treatment which delays melatonin synthesis. On the other hand, the LH surge terminated normally despite extended light exposure, if the rats were injected with melatonin at 19.00 h, when the dark phase usually begins. Melatonin injections during the standard photophase, i.e. at 13.00 or 17.00 h, blocked or prematurely terminated the LH surge, respectively. However, these effects probably do not represent a physiological function of melatonin, since its synthesis does not accelerate normally until after dark. 5 out of 14 pinealectomized rats showed altered patterns of preovulatory LH secretion 2 months after surgery. Since melatonin has been reported to block serotonin receptors, and serotonin stimulates phasic secretion of LH, we tested the ability of quipazine, a serotonin receptor agonist, to antagonize the inhibitory effect of melatonin on the LH surge. Quipazine given at 15.30 h blocked the inhibitory effect of melatonin administered at 16.00 h. The serotonin agonist partially restored LH levels in proestrous rats when it was given 30 min after melatonin. Therefore, the inhibitory effect of melatonin on phasic secretion of LH may result from an action upon serotonin-containing neurons. These findings taken together suggest that the pineal gland, ostensibly through the action of melatonin, contributes to termination of phasic LH secretion and thereby participates in entrainment of the LH surge to the photoperiod in the female rat.

Circadian Pattern of Plasma Melatonin Concentrations during Four Phases of the Human Menstrual Cycle

“…In women, LH, and by inference GnRH, pulse frequency varies by menstrual phase [37], Therefore, the participation of melatonin in the control of the menstrual cycle via hypothalamic mecha nisms has been proposed. However, the present data do not support the hypothesis that the luteal phase slowing of LH pulse frequency is attributable to an augmentation of nocturnal melatonin secretion [11], Our results cannot adequately address the question of whether nocturnal melatonin secretion declines in advance of the LH surge or influences the circadian phase position of the LH surge [7,18] because characterization of the melatonin rhythm during the late follicular phase was not con fined to the 24-hour period immediately preceding the onset of the LH surge. While pinealectomy can disrupt the entrainment of estrus events to seasonal or circadian cues, the available data do not suggest that this desynchronization prevents estrus cy clicity [38,39].…”

“…It is not known which, if any, aspect(s) of the circadian rhythm of melatonin convey important photoperiodic informa tion in humans. In mice and sheep, duration seems to be the critical variable [15,16], while amplitude can vary widely with out apparent effect [17], In rats, the circadian phase of melato nin appears to contribute vital information [18]. We thus felt that in order to examine critically the question of whether mela tonin secretion varied across the human menstrual cycle, it would be necessary to define the circadian melatonin rhythm in terms of duration, amplitude, and circadian phase position.…”

Sexually Dimorphic Modulation of GABAA Receptor Currents by Melatonin in Rat Gonadotropin-Releasing Hormone Neurons

“…The falling phase, which is caused by the decline of the activity of GnRH neurons, would be determined at least in part by the activity of GABA A receptors. The inhibitory action of melatonin is also demonstrated by the experiment that exogenous melatonin facilitates the offset of LH surge [7]. We can therefore postulate that melatonin decreases the activity of GABA A receptors through MT2, thereby inhibiting the neuronal excitability.…”

“…It is also suggested that the GABAergic system plays a role in the luteinizing hormone (LH) surge [5,6], though its precise mechanism has not been clarified. Furthermore, pineal hormone melatonin is involved in the regulation of reproductive functions, including the timing of the LH surge [7][8][9] and the modulation of circadian rhythms in mammals [10][11][12][13]. There are several possible sites of melatonin action.…”

DL- -Tocopherol acetate mitigates maternal hyperthermia-induced pre-implantation embryonic death accompanied by a reduction of physiological oxidative stress in mice

“…On the other hand, melatonin is a water-soluble hormone, and it was necessary to inject it six times at 2-h interval to achieve a beneficial effect (Matsuzuka et al 2005b). In addition, several studies have pointed out adverse effects of exogenous melatonin administration; melatonin injections in adult females disrupt the normal oestrus cycle by disturbing the secretion of LH-releasing hormone, resulting in low fertility in rats (Walker et al 1982, Rivest, 1987. In contrast, since TA is a lipid-soluble vitamin, the effects of TA administration are longer lasting and even a single dose can be effective.…”