Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

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Prolactin: Structure, Function, and Regulation of Secretion

I Introduction UNTIL 35 yr ago, most scientists did not take research on the pineal gland seriously The decade beginning in 1956, however, provided several discoveries that laid the foundation for what has become a very active area of investigation These important early observations included the findings that, 1), the physiological activity of the pineal is influenced by the photoperiodic environment (1–5); 2), the gland contains a substance, N-acetyl-5-methoxytryptamine or melatonin, which has obvious endocrine capabilities (6, 7); 3), the function of the reproductive system in photoperiodically dependent rodents is inextricably linked to the physiology of the pineal gland (5, 8, 9); 4), the sympathetic innervation to the pineal is required for the gland to maintain its biosynthetic and endocrine activities (10, 11); and 5), the pineal gland can be rapidly removed from rodents with minimal damage to adjacent neural structures using a specially designed trephine (12) Since the mid 1960s, research on t

Pineal Melatonin: Cell Biology of Its Synthesis and of Its Physiological Interactions*

Sleep and the Price of Plasticity: From Synaptic and Cellular Homeostasis to Memory Consolidation and Integration

Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. This is achieved by ocular photoreception relaying signals to the suprachiasmatic nucleus (SCN) in the hypothalamus. Signals from the SCN cause the synchronization of independent circadian clocks throughout the body to appropriate phases. Signals that can entrain these peripheral clocks include humoral signals, metabolic factors, and body temperature. At the level of individual tissues, thousands of genes are brought to unique phases through the actions of a local transcription/translation-based feedback oscillator and systemic cues. In this molecular clock, the proteins CLOCK and BMAL1 cause the transcription of genes which ultimately feedback and inhibit CLOCK and BMAL1 transcriptional activity. Finally, there are also other molecular circadian oscillators which can act independently of the transcription-based clock in all species which have been tested.

https://www.springer.com/cda/content/document/cda_downloaddocument/9783642259494-c1.pdf?SGWID=0-0-45-1387410-p174273964

Molecular components of the mammalian circadian clock

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Beck Depression Inventory-IIについての一考察

There are many situations in which it would be useful to know the phase state of the biological clock. It is recognized that measurement of melatonin levels can provide this information, but traditionally blood has been used for the analysis, and there are many problems in extending the measurements into the home or field situations. The aim of this study was to develop and validate a salivary melatonin radioimmunoassay and to compare results obtained against a plasma assay for determining the onset of melatonin secretion. The assay developed was sensitive (4.3 pM) and required only 200 microliters of sample. A rhythm in melatonin was detected in saliva, peaking at approximately 120 pM or 30% of the plasma levels. Using an objective criterion for determining the onset of secretion (mean +/- 2 standard deviations of three daytime samples), the time of onset was shown to exhibit low intraindividual variability (coefficient of variation = 1.5%-4.3%). The time of onset determined using saliva was significantly correlated with the plasma onset (r = .70, p < .05). The onsets determined were 22:30 h +/- 22 min for the saliva and 21:50 h +/- 16 min for plasma for 17 subjects. Similarly, the acrophases of the saliva and plasma melatonin rhythms were significantly correlated. Neither posture alone nor changes in posture affected the calculation of the onset of melatonin secretion using the saliva approach. Very high saliva flow rates induced by citric acid resulted in lower melatonin concentrations compared to the gentle chewing on parafin film. These results firmly establish the use of salivary melatonin measurements for phase typing of the melatonin rhythm in humans.

Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin

The effects of melatonin feeding on serum PRL and gonadotropin concentrations and on the reproductive activity of seasonally anestrous sheep were examined. Ten maiden Border Leicester X Merino ewes (18 months) were acclimatized to 16 h of light daily (from 0300–1900 h) for 4 weeks. Five of the animals were then fed pellets treated with melatonin (2 mg/ day); the remainder received untreated pellets daily at 1100 h for 103 days. Seventeen days after the commencement of treatment, serum PRL levels were found to be significantly lower between 1500–1900 h and 2400–0800 h (P < 0.05) in the melatonin- fed group compared to untreated animals. By day 31 and on all subsequent occasions tested up to day 99, serum PRL levels were lower (P < 0.01) in the melatonin-fed animals throughout the entire 8-h sampling period (0900–1700 h). The feeding of melatonin had no apparent effect on the baseline serum levels of either FSH or LH, the frequency and amplitude of the LH peaks, or the changes evoked in serum PRL after the ...

Effect of melatonin feeding on serum prolactin and gonadotropin levels and the onset of seasonal estrous cyclicity in sheep.

The development of rhythmic 6-sulfatoxymelatonin excretion in urine was studied in healthy full-term and premature infants during the first 12 months of life. There was little evidence of rhythmic 6-sulfatoxymelatonin excretion before 9 to 12 weeks of age in full-term infants. Over this period, excretion increased five to six times compared to the excretion at 6 weeks (08 +/- 103 vs. 2973 +/- 438 pmol/24 h) with the major proportion of the hormone metabolite being excreted between 0200-1000 h. At 24 weeks of age, total 6-sulfatoxymelatonin excretion was 25% of adult levels. Premature infants (51 +/- 4 days premature) had a delay in the appearance of rhythmic 6-sulfatoxymelatonin of approximately 9 weeks. Even after correcting for gestational age or length of time at home, the premature infants were found to have a 2-3 week delay in the development of 6-sulfatoxymelatonin rhythmicity compared to full-term infants. These results provide evidence that neural centers responsible for rhythm generation and/or the pineal gland fail to accelerate their development after premature delivery. This may be due to the environment the infants are exposed to during their stay in hospital, particularly the pattern and intensity of lighting.

Development of melatonin production in infants and the impact of prematurity.

A specific practical radioimmunoassay suited to determinations of melatonin in both tissues and body fluids is described. The rabbit antibody employed was raised to an antigen formed by condensation between N-acetylserotonin and the Mannich adduct of bovine serum albumin and formaldehyde. Substitution was shown by protonmagnetic resonance spectroscopy to occur exclusively at die 4 position of the indole nucleus. The antibody reacted with a variety of N-acetylated indoles, and absolute specificity was dependent upon the extraction procedure and column (Lipidex 5000) chromatography. In addition to the usual reliability criteria, the validity of the assay was checked by gas chromatography- mass spectrometry using [2H3]melatonin as an internal standard, the preparation of which is described. The occurrence of melatonin in the plasma of man, sheep, rat and chicken was confirmed, and its presence in the plasma of the pig (22–76 pg/ml), donkey (24–128 pg/ml), cow (20–320 pg/ml), camel (29–221 pg/ml) and a scinci...

A specific radioimmunoassay for melatonin in biological tissue and fluids and its validation by gas chromatography-mass spectrometry.

Shorter wavelength light has been shown to be more effective than longer wavelengths in suppressing nocturnal melatonin and phase delaying the melatonin rhythm. In the present study, different wavelengths of light were evaluated for their capacity to phase advance the saliva melatonin rhythm. Two long wavelengths, 595 nm (amber) and 660 nm (red) and three shorter wavelengths, 470 nm (blue), 497 nm (blue/green), and 525 nm (green) were compared with a no-light control condition. Light was administered via a portable light source comprising two light-emitting diodes per eye, with the irradiance of each diode set at 65 lW/cm 2 . Forty-two volunteers participated in up to six conditions resulting in 15 per condition. For the active light conditions, a 2-hr light pulse was administered from 06:00 hr on two consecutive mornings. Half-hourly saliva samples were collected on the evening prior to the first light pulse and the evening following the second light pulse. The time of melatonin onset was calculated for each night and the difference was calculated as a measure of phase advance. The shorter wavelengths of 470, 495 and 525 nm showed the greatest melatonin onset advances ranging from approximately 40-65 min while the longer wavelengths produced no significant phase advance. These results strengthen earlier findings that the human circadian system is more sensitive to the short wavelengths of light than the longer wavelengths.

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David J. Kennaway

Papers

Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin

Effect of melatonin feeding on serum prolactin and gonadotropin levels and the onset of seasonal estrous cyclicity in sheep.

Development of melatonin production in infants and the impact of prematurity.

A specific radioimmunoassay for melatonin in biological tissue and fluids and its validation by gas chromatography-mass spectrometry.

Differential effects of light wavelength in phase advancing the melatonin rhythm