Aromatization of androgens to estrogens by the rat pineal gland

Résumé Des homogénats de glande pineale de rat mâle métabolisèrent de la testostérone-C¹⁴ in vitro en stradiol-C¹⁴ et en strone-C¹⁴. Les métabolites furent identifiés chiomatographiquement et dans le cas de l'stradiol par recristallisation à activité spécifique constante. La conversion de la testostérone en stradiol fut de 0.19–0.27% et en strone de 0.02–0.04%. Ces résultatsci indiquent que la pinéale ressemble à d'autres régions du cerveau soumises au contrôle de la sécrétion de gonadotropines.

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These studies were supported by grants from the Comisión Nacional de Estudios Geo-Heliofísicos, Argentina and the World Health Organization. D.P.C. and C.A.N. are established investigators of the Comisión Nacional de Estudios Geo-Heliofísicos. J.M.R. is an established investigator of the Consejo Nacional de Investigaciones Cientificas y Técnicas, Argentina.     

Melatonin biosynthesis in the mammalian pineal gland

Rhythmic production of melatonin by the mammalian pineal occurs in response to noradrenergic stimulation which produces a cascade of biochemical events within the pinealocyte. In the rat, massive changes in NAT activity result from an increase in intracellular c-AMP levels produced by a synergistic interaction whereby an alpha 1 activation amplifies beta-adrenergic stimulation. The intracellular events mediating this effect are described. A major aspect of the temporal control of melatonin production is the programmed down-regulation of responses to noradrenergic stimulation once the initial surge of c-AMP is produced. Noradrenergic activation of the gland also influences other enzymic functions, including tryptophan hydroxylase and HIOMT activities, and produces a dramatic increase in intracellular c-GMP levels. Other neurotransmitters and neuropeptides, e.g. VIP, may also influence pineal function and comparisons are made between the rat, the subject of the bulk of experimental studies, and other species.     

Melatonin biosynthesis in the mammalian pineal gland

Summary Rhythmic production of melatonin by the mammalian pineal occurs in response to noradrenergic stimulation which produces a cascade of biochemical events within the pinealocyte. In the rat, massive changes in NAT activity result from an increase in intracellular c-AMP levels produced by a synergistic interaction whereby an ₁ activation amplifies -adrenergic stimulation. The intracellular events mediating this effect are described. A major aspect of the temporal control of melatonin production is the programmed down-regulation of responses to noradrenergic stimulation once the initial surge of c-AMP is produced. Noradrenergic activation of the gland also influences other enzymic functions, including tryptophan hydroxylase and HIOMT activities, and produces a dramatic increase in intracellular c-GMP levels. Other neurotransmitters and neuropeptides, e.g. VIP, may also influence pineal function and comparisons are, made between the rat, the subject of the bulk of experimental studies, and other species.     

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.     

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.     

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.     

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.     

Ultrastructure of the pineal gland after hypohysectomy

Résumé Nous avons étudié les modifications de l'ultrastructure de la glande pinéale du rat après hypophysectomie et constaté: (a) une atrophie du réticulum endoplasmique, (b) réduction des ribosomes, (c) dépletion du matériel sécrétoire des granules, (d) altération des mitochondries, (e) réduction dans le volume des noyaux et des nucléoles et (f) un agrandissement de l'espace périvasculaire. Il est très probable que l'hypophyse antérieure est nécessaire pour maintenir la structure et la sécrétion de la glande pinéale, mais le mécanisme par quoi s'exerce ce contrôle reste encore inconnu.     

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.     

Evidence for a modulation of the stress response by the pineal gland

Summary Wistar rats show a circadian variation in their response to stress. Pinealectomy exacerbates stress-induced gastric ulceration in rats. This effect is counteracted by melatonin administration.     

Evidence for a modulation of the stress response by the pineal gland

Wistar rats show a circadian variation in their response to stress. Pinealectomy exacerbates stress-induced gastric ulceration in rats. This effect is counteracted by melatonin administration.     

Central neural control of pineal melatonin synthesis in the rat

To investigate a possible central neural influence on nocturnal pineal metabolic activity in rats, 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 nocturnal pineal indole metabolism.     

Morphological changes in the pineal gland of the albino rat by hypophysectomy and ovariectomy

Zusammenfassung Die dunklen Pinealzellen waren nach Hypophysektomie beträchtlich vermehrt, während die Vesikeln in den sympathischen Nervenendigungen vermindert waren. Auch nach Ovariektomie waren die dunklen Pinealzellen in geringerem Ausmass vermehrt, ohne dass die Vesikeln vermindert waren. Die osmiophile Granula war sehr spärlich.     

Evidence for in vitro release of neurophysin by the rat pineal gland

Summary Cultured pineal ependymal cells from rat fetuses release into their incubation media immunoreactive neurophysin. The presence of neurophysin was assessed by radioimmunoassay. The culture medium was found to contain 440 pg neurophysin per mg protein.