The expression of somatostatin mRNA was investigated in rat pineal cells after 1 week in culture, using reverse transcription of mRNA into cDNA and the polymerase chain reaction. The positive expression in cultured pineal cells demonstrates the capacity of this gland to synthesize somatostatin in denervated cells. Thus, apart from the neural origin of pineal somatostatin, which has been described in detail in the bovine species, a parenchymal source is demonstrated.
Regional distribution of immunoreactive somatostatin (IRS) and melatonin were investigated in the bovine pineal gland. The total IRS and melatonin content ranged from 0.26 to 2.28 pmol, and from 19.4 to 42.7 pmol, respectively, per bovine pineal. Reverse phase liquid chromatography of pineal extracts demonstrated that more than 90% of IRS coeluted with synthetic somatostatin-14 and somatostatin-28. While the IRS content was shown to vary considerably throughout the gland, with a constant and marked maximal concentration at the proximal end of the pineal, the maximal melatonin concentration appeared in the central part of the gland, coinciding with the total protein distribution. The existence of the highest levels of pineal IRS near the habenular commissure, where the afferent fibers of the central pinealopetal innervation enter the gland, suggests that pineal somatostatin may be, at least in part, of neural origin.
Objective: To study circadian levels of melatonin in primary hypogonadic adult men before and after testosterone treatment. Design and methods: Circadian serum melatonin profiles were studied in six men with primary hypogonadism before and during testosterone substitution and compared with an age-matched control group (n ¼ 6). Results: Hypogonadal patients had higher plasma melatonin concentrations than the control group during day time (34:2 Ϯ 8:8 compared with 5:4Ϯ 0:5 ng/l, means Ϯ S.D.; P < 0:005) and night-time (74:8 Ϯ 34:5 compared with 30:8 Ϯ 3:2 ng/l). A 3 months course of testosterone replacement treatment in the hypogonadal group was followed by a diminution of the amplified melatonin circadian rhythm, with lower mean values both during the day (34:2:8 Ϯ 8 compared with 12:7 Ϯ 2:45 ng/l, P <0:001) and at night (74:8 Ϯ 34:5 compared with 41:5 Ϯ 13:5 ng/l, P <0:01), and a decrease in the total area under the curve (958 Ϯ 318 compared with 475:5 Ϯ 222:9, P ¼ 0:046). There was a significant negative correlation between melatonin (r ¼ ¹0:69) and testosterone concentrations. Conclusions: These data indicate that diminished testosterone in male primary hypogonadism is associated with enhanced plasma levels of melatonin, and that testosterone substitution treatment induces a deamplification of the circadian rhythm of melatonin values in humans.
Immunoreactive somatostatin (IRS) has been previously demonstrated in the pineal gland of different rodent species, and we observed a 24-hr rhythm in rats. Recent data suggest that the peptide may represent a neurotransmitter in the so-called peptidergic nerves of the central, pinealopetal innervation of the epiphysis, which may modulate the activity and secretion of the gland. We investigated whether 24-hr changes of pineal IRS content occurred in Syrian hamsters, gerbils, and mice. Adult males, kept in a 14:10 LD photoperiod, were decapitated at 4-hr intervals throughout a 24-hr period. Pineals and median eminences were analyzed for IRS by radioimmunoassay. No significant changes in the median eminence content of IRS with time was observed. As previously described in rats, a statistically significant rhythm of IRS was observed in the pineal of hamsters and mice, with a peak at 2000 hr (mice 51.7 +/- 5 pg/pineal; hamsters 26.3 +/- 4.6) and a nadir at 2400 hr (mice 30.8 +/- 1.4) or 0400 hr (hamsters 8.6 +/- 1). However, in the gerbil pineal IRS content remained unchanged throughout the period of study. Since the three species examined have very different melatonin cycles, it is suggested that the melatonin and IRS rhythms are unrelated and independently regulated events within the pineal gland.
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