It is well known that the pineal gland can modulate the secretion of pituitary hormones. Melatonin, the main hormone produced by the pineal gland, acts at the hypothalamic site, whereas hypophyseal sensitivity to melatonin seems to change with age. To investigate the influence of pubertal development on the role of the pineal gland in the regulation of the secretion of pituitary hormones, FSH, LH, Prl, TSH and GH responses to melatonin were evaluated in a group of 9 prepubertal and 10 pubertal healthy subjects of both sexes. Melatonin was given im at a dose of 0.2 mg/kg body weight at 3 p.m. Venous blood samples were drawn \m=-\20,0, 20, 40, 60, 90, 120, 180 and 240 min, after melatonin injection. According to the same experimental protocol, venous blood samples were collected during a saline infusion on a separate occasion. FSH, LH, Prl, TSH and GH plasma levels were measured with RIA. In pubertal subjects, a significant rise in the mean Prl levels was seen 90 min after melatonin as compared with those during saline infusion. The Prl melatonin response area was significantly lower in prepubertal treated subjects and significantly higher in pubertal ones compared with the respective controls. The mean GH values showed a significant decrease 120 min after melatonin only in prepubertal subjects; no significant variations were seen in 8 of 10 pubertal subjects, whereas in the last 2 a marked increase was observed. Finally, under these conditions, melatonin did not influence the basal FSH LH and TSH levels.These results seem to suggest that hypophyseal hormone reponses change with pubertal development.

Recent reports point to a link between the pineal gland and the opioid system. In order to investigate this relationship, two separate studies were performed on humans. Beta-endorphin plasma levels were determined after melatonin administration (0.2 mg/kg b.w. i.m. at 2 p.m.). Melatonin serum values were evaluated after administration of FK 33-824, a met-enkephalin analogue (0.3 mg i.v. infusion at 9 a.m.). A significant decrease of beta-endorphin plasma levels was observed 120 minutes after melatonin injection. Melatonin release was stimulated by FK 33-824, with a peak at 30 minutes. The present results provide evidence of the inhibitory effect of melatonin on beta-endorphin secretion and the stimulatory action of the opioid peptides on the pineal gland. However, further studies will be required to clarify the relationship between the opioid system and the pineal gland.

The mechanisms by which tetrahydrocannabiol (A'-THC) affects some neuroendocrine activities have not yet been clarified. Its effects cannot be prevented by pretreatment with a-methyltyrosine, which reduces brain concentrations of norepinephrine and dopamine (Hollister 1971). At present, the existence of an endogenous agonist cannot be excluded. To investigate whether its effects involve the participation of the pineal gland, the response of melatonin (the main pineal hormone), to A'-THC was evaluated in nine agreeing healthy male volunteers, aged between 29 and 33. The substance was administered at 3 p.m. through a 1 g cigarette containing 1% A 9 -THC. Venous blood samples were drawn from an indwelling catheter in an antecubital vein -20, 0, 20, 60 and 120 mins. after drug administration. According to the same experimental protocol, on the preceding day the test had been performed after smoking one normal cigarette. The whole test was carried out in summer. Sera were separated by centrifugation and stored at -20° C until assayed. Melatonin serum values were measured by means of the RIA method described by Wetterberg, Erickson, Friberg and Vangbo (1978), using commercially available kits (WHBSweden) when the extracts showed melatonin values higher than detection limit, samples were measured after an adequate dilution. Data were analyzed by Student's t-test and results reported as the mean + SD. A very high significant increase (P < 0.001) of melatonin serum mean levels, in comparison to the values observed during saline infusion, was noticed in eight of the nine subjects after A'-THC administration; the highest values were obtained at 120 mins. from administration (Table 1).In contrast, the last case showed high basal levels of melatonin (289.3 -321.3 -157.0 -72.5 -181.2 pg/ml, respectively at -20, 0, 20, 60, 120 mins.) without evidence of endocrine or psychiatric disorders, and melatonin peak was significantly inhibited (P < 0.001) by A'-THC, with the lowest levels reached 60 mins. later (304.2 -311.7 -294.2 -306.0 -314.8 pg/ml respectively at-20, 0, 60, 120 mins.).These preliminary results are difficult to interpret moreover, at present we are unable to explain the hight melatonin basal level observed in the last case. However, the present data, suggest that A'-THC may regulate the activity of the pineal gland either by stimulating or inhibiting melatonin secretion, and that melatonin response to A'-THC seems to depend upon its basal levels. MoreDownloaded by: University of Illinois. Copyrighted material.

It has been reported that adult obese subjects present a reduced growth hormone secretion. As no data are available in the pubertal period, which is characterized in lean subjects by an increased spontaneous growth hormone secretion, the growth hormone circadian concentration was studied in a group of 18 obese male subjects in different pubertal stages, and compared to 26 age-matched control subjects. The data observed evidenced no statistically relevant differences regarding LH and FSH circadian secretion and morning testosterone concentration. On the contrary a statistically significant (p less than 0.02) difference in growth hormone 24 h integrated concentration was evident, particularly in prepubertal subjects; the sleep-related peak was evident in 28% of obese subjects and in 85% of controls. Sm-C/IGF-I concentration was similar to the concentration observed in controls in the prepubertal stage, but did not show the expected increase in the late puberty. Auxological data, performed on a sample of 80 subjects, showed both advanced height and bone age at beginning of puberty, and a trend toward a reduction of percentile for height in parallel with the pubertal maturation, suggesting that pubertal growth spurt in obese subjects is at least less pronounced than in lean subjects. It is concluded that GH and Sm-C/IGF-I secretion is impaired during puberty in obese subjects, leading to a reduced growth rate, while in the prepubertal period factors other than GH may replace or even potentiate its action.

It has been known for many years that the pineal gland is involved in regulating tumor growth. In order to evaluate the functional activity of the pineal gland in neoplastic diseases, melatonin serum levels and its light/dark rhythm have been determined with the RIA method in patients affected by various forms of tumor. Irrespectively of the type of the tumor and of its localization, existence of two subpopulations has been observed within the oncologic patients, the former with normal levels of melatonin, and the latter with high ones. The light/dark rhythm of melatonin was anomalous in some cases. An evident decrease of serum melatonin values was seen after chemotherapy. It might be interesting to establish whether melatonin levels may conditionate the prognosis of patients with cancer.