Long-term food restriction is known to inhibit development and aging in the rat. These actions may be mediated by the pineal hormone, melatonin, whose secretion is increased by food restriction. This mechanism was investigated by studying the effects of pinealectomy in ad libitum fed and food restricted rats of both sexes living under normal conditions of temperature (23 degrees C) and lighting (12 h light:12 h dark cycle) over a period of 400 days. Pinealectomies were performed at the age of 5 days. Pinealectomy did not affect the amount of food eaten per day. Vaginal opening occurred at age 35 days in ad libitum fed female rats and was delayed to 49 days (P < 0.001) in rats whose food intake was restricted by 35%, but only to 41 days (P < 0.001) if food restricted (FR) rats were pinealectomized (Px). The inhibitory effect of food restriction on body growth and tail tendon collagen fibre aging was the same in both intact and pinealectomized rats. At the conclusion of the study in middle age at 400 days, plasma melatonin levels 4 h into the dark cycle were higher in food restricted than in ad libitum fed rats (P = 0.015). This study provides evidence for a role of the pineal in mediating the inhibitory action of food restriction on vaginal opening, but not on body growth or collagen aging in tail tendon up to middle age.

The activity of serotonin N-acetyltransferase in the rat pineal is regulated through a synergistic action of norepinephrine on alpha 1- and beta 1-adrenoceptors. Rat pineal hydroxyindole-O-methyltransferase (HIOMT) activity is also responsive to the beta 1-adrenoceptor, while melatonin synthesis and indoleamine release in certain species is apparently under alpha 1-adrenoceptor control. The present study reports that the simultaneous administration of doxazosin (a selective alpha 1-adrenergic antagonist) and metoprolol (a selective beta 1-adrenergic antagonist) reduces peak HIOMT activity significantly more than either agent alone, indicating that rat pineal HIOMT is also subject to synergistic alpha 1- and beta 1-adrenergic regulation. The relationship between alpha 1-adrenoceptor stimulation, serotonin release, and HIOMT activity is considered, following the observation that nocturnal HIOMT activity is elevated in serotonin-depleted pineal glands.

Pineal hydroxyindole-O-methyltransferase (HIOMT) has been reported to show a diurnal rhythm activity in the rat, although this is not fully confirmed. The present study reexamines this issue and reports a distinct diurnal rhythm in rat pineal HIOMT. Peak enzyme activity occurs 5 hr after the onset of darkness, followed by two lesser bursts of activity preceding each change in the photoperiod. The approximately 18-fold increase in methylating capacity at night represents the greatest variation in HIOMT activity thus far reported in the rat and may be attributed to the age, weight, and housing regimen of the animals used.

5‐hydroxytryptophol (5HTL) occurs in the pineal gland of the rat at levels comparable to those of melatonin, yet few studies have been conducted to investigate 5HTL as a potential alternative pineal hormone. In this study the pineals of 90‐day‐old male Sprague Dawley rats have been assayed by high performance liquid chromatography coupled with electrochemical detection. Significant (P < .0001) circadian variation was measured in 5HTL levels, and a fivefold plateau elevation occured during the middle of the light period. By comparison with the timing of the variations in N‐acetyl serotonin and melatonin levels, it is suggested that 5HTL may not be regulated by simple competition with N‐acetyl transferase for the common substrate 5HT but may, in fact, be regulated independently. Literature supporting such a suggestion, and a model incorporating it, are presented for discussion.

Despite intensive investigation, particularly over the past fifteen years, many aspects of pineal function with respect to mammalian physiology remain obscure. Much of this work is reviewed and particular attention focussed on indole metabolism within the pineal gland. Emphasis is placed on the development of new analytical techniques with especial reference to high performance liquid chromatography coupled with electrochemical detection. The growth in knowledge regarding pineal indole synthesis which can be attributed to the use of this technique is discussed. The possibility that pineal indoles other than melatonin may function as hormones or neuromodulators is considered. A functional role for 5-hydroxytryptophol as a neuromodulator, possibly associated with diffuse neuroendocrine function (amine precursor, uptake and decarboxylation, APUD) is suggested.