Melatonin and aging. A brief survey.

The relationship between the pineal gland and aging has been assumed already nearly a century ago. Recently, melatonin was considered by some authors as a "wonder drug." The present paper tries to summarize the relationship between melatonin and aging in three points.

Melatonin secretion of the rat pineal gland in response to norepinephrine in different types of the anovulatory syndrome.

Earlier experimental results show the role of altered pineal function in the development of the constant estrous-anovulatory (CEA) state induced by neonatal androgen sterilization (NA) or in the spontaneously developed anovulatory syndrome in the aging rat (AG-CEA state). Since norepinephrinergic (NE) innervation of pineal gland represents the main stimulus for melatonin secretion in mammals, in the present experimental series, the reactivity of pineal tissue to NE was investigated in in vitro perifusion system in rats suffering from NA-CEA or AG-CEA state, using the model of pineal body deprived from neural inputs. The data indicate that the 'melatonin deficiency' observed in the 2 types of anovulatory syndrome (NA-CEA and AG-CEA states) is due to disturbance of norepinephrinergic innervation of the pineal gland rather than to deficient secretory capacity of pineal tissue.

Inhibition of cold stimulated thyrotropin release in rats by neurotropic drugs: specific or unspecific effect?

Male Wistar Olac rats were kept in stainless steel cages at 24 +/- 1 °C. Three days before the experiment they were transferred into another room and kept 3 days at 30 °C. On the day of experiment, groups of 14-16 animals each were injected i.

Influence of serotonergic neurons and of pineal gland on the development of the neonatal androgen sterilization syndrome in the rat.

The effect of the removal of pineal gland, performed in adult age or during perinatal life, was investigated in the neonatal androgen sterility (NA-CEA) syndrome, in combination with drugs acting on serotonergic neurons. Perinatal pinealectomy (Px) was more potent in preventing the development of NA-CEA state than Px performed in the adult age. These data indicate that the masculinized hypothalamus becomes less sensitive to pineal influences during the lifespan.

Long-term effect of perinatal neurochemical lesions of brain monoaminergic neurons on body growth, growth hormone secretion and thyroid activity.

In the present experiments, extended studies were performed on long-term effect of perinatal neurotoxic damage of brain monoaminergic neurons exerted on Grown Hormone (GH) and on Thyrotrophic Hormone (TSH) secretion. Neurotoxins were applied for selective destruction of the different components of the monoaminergic neuron system. Deficient GH secretion and reduced TSH-mobilizing capacity were observed in consequence of perinatal injury of dopaminergic neurons, meanwhile in perinatal serotonergic lesion bearing rats, reduced GH secretion was associated with increased reactivity of the TSH-mobilizing mechanism.

Studies and reevaluations of some aspects on thyroid function after superior cervical sympathetic gangliectomy in rats.

The results of 11 experiments in a total of 571 rats (initial body weight of 150-250 g) are reported and some findings differing from those by others are discussed. It was repeatedly found that the animals after bilateral or even unilateral superior cervical sympathetic gangliectomy (GX) did not gain body weight during the first week after surgery. Though they started to grow later, for several weeks their body weight remained significantly less than that of sham operated controls (SH).

Impaired thyroid function provoked by neonatal treatment with drugs affecting the maturation of monoaminergic and opioidergic neurons.

The aim of the present work was to study the basal secretion rate and the reactivity of the TSH-thyroid axis in adult rats neonatally exposed to drugs influencing monoaminergic and opioidergic neurons. The early postnatal administration of drugs antagonistic with the dopaminergic or serotoninergic neurons resulted in a persistent higher rate of basal secretion of TSH, while the administration of drugs synergistic with the monoaminergic neuron systems was weakly influential in this respect. The exposure to opioids in the perinatal period resulted in a permanent reduction of serum TSH levels which was even more pronounced when the exposure to morphine was advanced to the fetal period of life.

Creatine kinase in hypo- and hyperthyroid rats under consideration of the circadian oscillations.

Thyroxine level (T4) and total creatine kinase-activity (CK) were measured in serum samples from male Wistar-rats to investigate the relationships of serum titers after exposure to cold and thyroidectomy (TX). 72 hours exposure to cold (10 degrees C) produced a statistically significant elevation of T4 and a diminuation of CK-activity. In contrast to this protocol, TX (90 days after operations) reduced the T4 level and enhanced the CK-activity.

Changes in the daily rhythm of serum testosterone levels following superior cervical sympathetic ganglionectomy in the cold-exposed rat: the role of the pineal.

The effect superior cervical sympathetic ganglionectomy (Gx) exerted on the daily rhythm of serum testosterone levels was investigated in cold-exposed rats. Rhythmic changes in pineal and pituitary weights were also measured. 1.

[Thyroid reactions in Wistar rats during the circadian rhythm after ganglionectomy at normal temperature and under cold exposure with regard to the influence of the epiphysis cerebri].

Serum thyroxin (T4), serum TSH, and pituitary TSH were measured by radioimmunoassay (RIA) and serum cholesterol by Liebermann-Burchard reaction in rats 4 times a day (light-dark cycle: 14 L: 10 D) after gangliectomy (bilateral extirpation of the Ganglia cervicalia superiora) at cold and normal temperature conditions. 80 male Wistar rats were divided into 4 groups: sham-operated group, 24 degrees C (297 K); sham-operated group, 10 degrees C (283 K); gangliectomy, 24 degrees C (297 K), and gangliectomy, 10 degrees C (283 K). We have sacrificed the rats 30 d after operations at the following day-times: middle light, middle darkness, 1 h after light "on" and 1 h after light "off" (they were exposed to cold 72 h before killing).

Studies on the inhibitory effect of apomorphine and bromocryptine on basal and TRH induced level of TSH and PRL in hypothyroid rats under pentobarbiturate anesthesia.

Groups of male rats were inserted with polyethylene tubings into femoral artery and vein under pentobarbiturate anesthesia and small blood samples were frequently taken for the estimation of TSH and PRL under maintaining isovolemia. After a single injection of apomorphine (12 mg kg-1) or bromocryptine (20 mg kg-1) much more expressed effect of these drugs on a decrease of PRL level in plasma was found than that on a decrease of TSH level and similar observation was made with the use of continuous i.v.

Opioidergic regulation of thyroid activity: possible interference with the serotonergic system.

Acute systemic administration of (D-Met2, pro5-NH2)-enkephalin (ENKamide), a very potent enkephalin analog, and of morphine not only diminished the basal levels of serum TSH under resting conditions, but also significantly reduced the enhanced serum TSH concentrations induced by goitrogen treatment or by bilateral thyroidectomy. Acute administration of opiates failed to inhibit the pituitary TSH response to exogenous TRH administration. The TSH release-inhibiting effect of ENKamide was reversed by pretreatment with the serotonin synthesis inhibitor, para-chlorophenylalanine (pCPA) or with the central serotonin receptor blocker, metergoline.

Central nervous regulation of pituitary TSH response induced by thiouracil treatment or by thyroidectomy.

The serotoninergic neuron system of the midbrain and hypothalamus was previously shown to inhibit the basal secretion of the TRH-TSH-thyroid axis. The aim of the present study was to investigate the influence of the serotoninergic system on the TSH response of the adenohypophysis to specific loads. Serum TSH levels were determined 7 days after thyroidectomy or the beginning of thiouracil administration.

Role of the serotoninergic neuron system of the brain stem on the release of thyrotrophic and luteinizing hormone.

1. Decrease of brain serotonin concentration, elicited by either parachlorophenylalanine treatment, surgical interruption of the ascending serotoninergic fibres, or by pinealectomy provokes an enhanced release both of TSH and LH. 2.

Inhibitory role of brain stem serotoninergic neuron system on thyroid function in rat.

Thyroid function was investigated in adult male rats following the use experimental procedures which inhibit the activity of serotoninergic neuron system. Pharmacological blockade of the biosynthesis of sertonin by repeated administration of para-chlorophenylalanine (pCPA), or interruption (by Halász knife) of the serotoninergic pathways of the brain stem which terminate on hypothalamic nuclei equally resulted in an augmentation of the following parameters of hypothalamo-hypophysial-thyroid activity: T/S ratio, pituitary and blood TSH levels and blood thyroxine concentration as well as TRH content of the hypothalamus. The results suggest that the central nervous serotoninergic neuron system plays an inhibitory role in the regulation of TSH secretion, presumably acting upon the hypothalamus, thereby inhibiting hypothalamic TRH secretion.

Effect of the fungal toxin (zearalenone) on the reproductive system and fertility of male and female rats.

The fertility-inhibiting effects of long-term (8 weeks) consumption of maize infected with a fungus producing F2 toxin (zearalenone) was studied in adult male and female albino rats. The fertility rate was further decreased by 25-30% if the animals were kept on contaminated diet up to 14 weeks. The gonadal weight was decreased, follicular maturation and spermatogenesis were disturbed.

Effect of melatonin on induction of ovulation in the light- induced constant estrous-anovulatory syndrome and possible role of the brain serotoninergic system.

Continuous light (CL) induces constant estrous anovulatory (CEA) syndrome and blockade of pineal gland activity. Chronic treatment with metatonin is able to overcome the anovulatory state in about 70% of CL-CEA rats, and the luteinizing effect of melatonin is significantly counteracted either by feeding the animals with a tryptophan-poor diet or by injecting methiothepin, a blocker of central serotoninergic receptors. It appears that melatonin elicits luteinization in CL-CEA rats through the brain serotoninergic system.

The role of the pineal gland in the regulation of LH-release in rats with different types of the anovulatory syndrome.

The effect of different doses of testosterone propionate was investigated in provoking the development of the constant estrous anovulatory (CEA) syndrome in the rat. A direct relationship was observed between the dose of neonatally administered androgen (NA) and the percentage occurrence of this syndrome. Pinealectomy and superior cervical sympathetic ganglionectomy elicited the development of marked thecal luteinization in the NA-CEA rat, but the formation of corpora lutea was limited after these operations.