Central neural control of pineal melatonin synthesis in rat

Summary To investigate a possible central neural influence on nocturnal pineal metabolic activity, frontal transsections of the stria medullaris thalami were conducted. Enzymes involved in melatonin synthesis, i.e. N-acetyltransferase and hydroxyindole-O-methyl-transferase, exhibited reduced activities in operated animals when compared to controls. These results indicate a modulatory role of central structures on noctural pineal indole metabolism.This study was supported by the Deutsche Forschungsgemeischaft and the Stifung Volkswagenwerk. The technical assistance provided by M. Henschel, I. v. Graevenitz and G. Schlich is gratefuly acknowledged.     

Antidepressant drugs elevate rat pineal and plasma melatonin

Summary Acute administration in the mid-light phase of a number of antidepressant drugs of different pharmacological profiles elevated pineal and plasma melatonin (measured by radioimmunoassay). Following chronic treatment with the tricyclic antidepressant clomipramine, the elevation was significantly reduced. This may be an effect of reduced -adrenergic receptor sensitivity after chronic clomipramine administration, analogous to other findings of reduced -adrenergic receptor binding and reduced noradrenaline-sensitive adenylate-cyclase response.These collaborative studies were made possible by a Twinning Grant from the European Training Programme for Brain and Behaviour Research; J.A. was supported by the Medical Research Council of Great Britain. We thank M. Lichtsteiner for excellent technical assistance. This paper was written during a Fellowship of the Swiss Biomedical Research Foundation to A.W.-J. Hofmann-LaRoche AG, Basel kindly provided the 1-5HTP-ester (Ro 11-5940) and Ro 11-2465, CIBA-Geigy AG, Basel, the maprotiline, clomipramine, and imipramine, USV, New York, the desmethylimipramine.     

Development of rhythmic melatonin synthesis in cultured pineal glands and pineal cells isolated from chick embryo

The chick pineal gland exhibits circadian rhythms in melatonin synthesis under in vivo and in vitro conditions. A daily rhythm of melatonin production was first detectable in pineal glands isolated from chick embryos at embryonic day 16 and incubated under a LD cycle. All pineal glands isolated from 17-day-old and older embryos were rhythmic while no gland isolated at embryonic day 14 and 15 exhibited a daily rhythm in melatonin synthesis. Melatonin production in static cultures of embryonic pineal cells was rhythmic over 48 h if the cells were kept under a LD cycle. When embryonic pineal cells were incubated in constant darkness the rhythm in melatonin production was damped within 48 h. These results suggest that chick pineal cells from embryonic day 16 onwards are photosensitive but that the endogenous component of the melatonin rhythm is not completely developed at that age. A soluble analogue of cAMP stimulated and norepinephrine inhibited melatonin synthesis in cultured embryonic pineal cells. These findings indicate that the stimulatory and inhibitory pathways controlling melatonin synthesis in the mature pineal gland are effective in pineal cells isolated from chick embryos at least 2 days before hatching.     

Effects of oestrogen and progesterone on rat pineal N-acetyl transferase activity and melatonin production

We have extended previous studies on pineal beta-receptors to include effects of oestradiol or PMSG treatment in the immature female rat. Neither manipulation has any effect on norepinephrine-induced N-acetyl transferase (NAT) activity in vitro. In the adult ovariectomised rat oestrogen/progesterone priming exerts a small sensitising effect to beta-stimulation with isoproterenol. Progesterone alone, in vitro, inhibits the release of melatonin from pineals of adult ovariectomised rats.     

Effects of oestrogen and progesterone on rat pineal N-acetyl transferase activity and melatonin production

Summary We have extended previous studies on pineal -receptors to include effects of oestradiol or PMSG treatment in the immature female rat. Neither manipulation has any effect on norepinephrine-induced N-acetyl transferase (NAT) activity in vitro. In the adult ovariectomised rat oestrogen/progesterone priming exerts a small sensitising effect to -stimulation with isoproterenol. Progesterone alone, in vitro, inhibits the release of melatonin from pineals of adult ovariectomised rats.The authors are grateful to J. Bradtke, D. de Ziegler and K.B. Ruf for their help, and to the Swiss National Science Foundation and to the Fonds Emil Barrell for financial support.     

Development of melatonin rhythm in the pineal gland and eyes of chick embryo

A melatonin rhythm was observed in the pineals of 18-day-old chick embryos incubated under a light-dark regime of 186 h. A low pineal melatonin content was found during the light phase of the day. Concentrations started to increase 2 h after dark onset and reached maximum levels after 4 h of darkness. The amplitude of the pineal melatonin rhythm increased considerably after 2 days and night-time concentrations in 20-day-old embryos were more than 5 times higher than in 18-day-old ones. Significant day/night differences in melatonin production were found both in pineals and eyes. Exposure of eggs to 1 h of light during the dark period decreased the high melatonin concentrations in the eyes but not in the pineals of the 20-day-old chick embryo. The results suggest that in this precocial bird at least part of the circadian system may already operate during embryonic life.     

Effects of sham-pinealectomy,performed under white and red light,on the melatonin content of rat pineal glands

Summary Sham-pinealectomy, performed under different light conditions in newborn and adult rats, is followed by changes of pineal activity resulting in variations of melatonin content. The pineal glands of rats sham-operated under white light produce significantly less melatonin. In contrast, glands of rats operated on under red light show a melatonin content corresponding to that of intact rats. This result implies that normal white light causes a disturbance in melatonin production by a non-retinal pathway.     

Maturation of the pineal melatonin rhythm in long- and short-day reared Djungarian hamsters

Summary Male Djungarian hamsters, reared under long (16L/8D) or short (10L/14D) days, were sacrificed at various ages during the day or night, or at night following a 30-min light pulse. The pineal melatonin rhythm matured similarly under long and short days by 20 days of age. The results are discussed in context of the hypothesis that melatonin mediates the photoperiod effects which forestall puberty in short-day reared hamsters.Supported by NIH research grant HD-05481.     

Maturation of the pineal melatonin rhythm in long- and short-day reared Djungarian hamsters

Male Djungarian hamsters, reared under long (16L/8D) or short (10L/14D) days, were sacrificed at various ages during the day or night, or at night following a 30-min light pulse. The pineal melatonin rhythm matured similarly under long and short days by 20 days of age. The results are discussed in context of the hypothesis that melatonin mediates the photoperiod effects which forestall puberty in short-day reared hamsters.     

Acute effects of unilateral or bilateral superior cervical ganglionectomy on rat pineal N-acetyltransferase activity and melatonin content

Summary Acute bilateral superior cervical ganglionectomy (SCGX) completely prevents the nocturnal rises in pineal N-acetyltransferase (NAT) activity and melatonin content in male rats kept in light-dark cycles of 1410. Unilateral SCGX causes the NAT and melatonin levels to be intermediate between those in sham-operated control rats and those in rats from which both ganglia had been removed.Supported by NSF, grant No. PCM 77-05734.     

Development of melatonin rhythm in the pineal gland and eyes of chick embryo.

A melatonin rhythm was observed in the pineals of 18-day-old chick embryos incubated under a light-dark regime of 18: 6 h. A low pineal melatonin content was found during the light phase of the day. Concentrations started to increase 2 h after dark onset and reached maximum levels after 4 h of darkness. The amplitude of the pineal melatonin rhythm increased considerably after 2 days and night-time concentrations in 20-day-old embryos were more than 5 times higher than in 18-day-old ones. Significant day/night differences in melatonin production were found both in pineals and eyes. Exposure of eggs to 1 h of light during the dark period decreased the high melatonin concentrations in the eyes but not in the pineals of the 20-day-old chick embryo. The results suggest that in this precocial bird at least part of the circadian system may already operate during embryonic life.     

Effect of removal of the Harderian glands on pineal melatonin concentrations in the Syrian hamster

Summary Peak melatonin levels which are normally present in male Syrian hamsters at 8 h after the onset of darkness in animals maintained under a lightdark cycle of 1410, were significantly decreased following the removal of the Harderian glands.Supported by NSF grant PCM 77-05734.     

The pineal and melatonin: Regulators of circadian function in lower vertebrates

Summary The pineal has been identified as a major circadian pacemaker within the circadian system of a number of lower vertebrates although other pacemaking sites have been implicated as well. The rhythmic synthesis and secretion of the pineal hormone, melatonin, is suggested as the mechanism by which the pineal controls circadian oscillators located elsewhere. Both light and temperature cycles can entrain the pineal melatonin rhythm. The pineal, therefore, acts as a photo and thermoendocrine transducer which functions to synchronize internal cycle with cycles in the environment. A model is presented which portrays the pineal as a major component of a multioscillator circadian system and which suggests how these multiple circadian clocks are coupled to each other and to cycles of light and temperature in the external world.     

The pineal and melatonin: regulators of circadian function in lower vertebrates

The pineal has been identified as a major circadian pacemaker within the circadian system of a number of lower vertebrates although other pacemaking sites have been implicated as well. The rhythmic synthesis and secretion of the pineal hormone, melatonin, is suggested as the mechanism by which the pineal controls circadian oscillators located elsewhere. Both light and temperature cycles can entrain the pineal melatonin rhythm. The pineal, therefore, acts as a photo and thermoendocrine transducer which functions to synchronize internal cycle with cycles in the environment. A model is presented which portrays the pineal as a major component of a 'multioscillator' circadian system and which suggests how these multiple circadian clocks are coupled to each other and to cycles of light and temperature in the external world.     

Acute effects of unilateral or bilateral superior cervical ganglionectomy on rat pineal N-acetyltransferase activity and melatonin content.

Acute bilateral superior cervical ganglionectomy (SCGX) completely prevents the nocturnal rises in pineal N-acetyltransferase (NAT) activity and melatonin content in male rats kept in light-dark cycles of 14:10. Unilateral SCGX causes the NAT and melatonin levels to be intermediate between those in sham-operated control rats and those in rats from which both ganglia had been removed.     

The pineal and melatonin: Regulators of circadian function in lower vertebrates

Summary The pineal has been identified as a major circadian pacemaker within the circadian system of a number of lower vertebrates although other pacemaking sites have been implicated as well. The rhythmic synthesis and secretion of the pineal hormone, melatonin, is suggested as the mechanism by which the pineal controls circadian oscillators located elsewhere. Both light and temperature cycles can entrain the pineal melatonin rhythm. The pineal, therefore, acts as a photo and thermoendocrine transducer which functions to synchronize internal cycle with cycles in the environment. A model is presented which portrays the pineal as a major component of a multioscillator circadian system and which suggests how these multiple circadian clocks are coupled to each other and to cycles of light and temperature in the external world.     

Pituitary control of androgen synthesis in the rat embryo]

Removal of the hypophysis by decapitation of the 19--or 20 days--old Rat embryo is followed by a significant decrease in the ability of the embryonic testis to synthesize testosterone and androstenedione from acetate in vitro. It is concluded that pituitary-testis relationships first appear at 19 days of intrauterine life.     

Concrement formation encountered in the rat pineal gland

Summary Morphological evidence is given for the concrement formation encountered in the rat pineal gland, the occurrence of which has not been reported so far (for the rat).     

Effects of estrogens and progesterone upon the biosynthesis of melatonin by the pineal gland

Zusammenfassung Da die Aktivität der Pinealdrüse bei weiblichen Ratten mit dem Cyklus wechselt, wurde die Wirkung von Oe tradiol und Progesteron auf ihre Aktivität bei kastrierten weiblichen Ratten untersucht. Oestradiol bewirkte Gewichtsabnahme und Funktionssteigerung, während Progesteron die Pinealis-Aktivität herabsetzte.