The Human Plasma Proteome History, Character, and Diagnostic Prospects

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

ContextIn young adults, sleep affects the regulation of growth hormone (GH)
and cortisol The relationship between decreased sleep quality in older adults
and age-related changes in the regulation of GH and cortisol is unknownObjectiveTo determine the chronology of age-related changes in sleep duration
and quality (sleep stages) in healthy men and whether concomitant alterations
occur in GH and cortisol levelsDesign and SettingData combined from a series of studies conducted between 1985 and 1999
at 4 laboratoriesSubjectsA total of 149 healthy men, aged 16 to 83 years, with a mean (SD) body
mass index of 241 (23) kg/m2, without sleep complaints or histories
of endocrine, psychiatric, or sleep disordersMain Outcome MeasuresTwenty-four–hour profiles of plasma GH and cortisol levels and
polygraphic sleep recordingsResultsThe mean (SEM) percentage of deep slow wave sleep decreased from 189%
(13%) during early adulthood (age 16-25 years) to 34% (10%) during midlife
(age 36-50 years) and was replaced by lighter sleep (stages 1 and 2) without
significant increases in sleep fragmentation or decreases in rapid eye movement
(REM) sleep The transition from midlife to late life (age 71-83 years) involved
no further significant decrease in slow wave sleep but an increase in time
awake of 28 minutes per decade at the expense of decreases in both light non-REM
sleep (−24 minutes per decade; P<001) and
REM sleep (−10 minutes per decade; P<001)
The decline in slow wave sleep from early adulthood to midlife was paralleled
by a major decline in GH secretion (−372 µg per decade; P<001) From midlife to late life, GH secretion further
declined at a slower rate (−43 µg per decade; P<02) Independently of age, the amount of GH secretion was significantly
associated with slow wave sleep (P<001) Increasing
age was associated with an elevation of evening cortisol levels (+193 nmol/L
per decade; P<001) that became significant only
after age 50 years, when sleep became more fragmented and REM sleep declined
A trend for an association between lower amounts of REM sleep and higher evening
cortisol concentrations independent of age was detected (P<10)ConclusionsIn men, age-related changes in slow wave sleep and REM sleep occur with
markedly different chronologies and are each associated with specific hormonal
alterations Future studies should evaluate whether strategies to enhance
sleep quality may have beneficial hormonal effects

https://jamanetwork.com/journals/jama/articlepdf/192981/JCI00039.pdf

Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men.

Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways.

Circadian genes, rhythms and the biology of mood disorders.

Summary
Objective Older adults are less responsive to the phase-shifting effects of light than younger subjects and may have difficulties adapting to abrupt time shifts. This study aims to determine whether the potent melatonin agonist agomelatine (S-20098) is capable of phase-shifting overt circadian rhythms in older adults.

Subjects and design  Eight healthy elderly men participated in a double-blind, two-period, cross-over study of 15 days of daily administration of either agomelatine (50 mg) or placebo at 1830 h.

Measurements  At the end of each treatment period, the 24-h profiles of body temperature and of the plasma levels of GH, PRL, cortisol and TSH were collected and sleep was monitored polygraphically.

Results  Phase-advances, averaging nearly 2 h, were observed for the temperature profile and for the variables characterizing the temporal organization of cortisol secretion following agomelatine administration. A similar trend was observed for the circadian rise of plasma TSH. There was no effect of agomelatine on any of the sleep variables. Agomelatine stimulated GH secretion during the wake period and was associated with a transient elevation of PRL levels.

Conclusions  Melatonin agonists such as agomelatine may be useful to phase-shift at least some overt circadian rhythms in older adults.

Phase-shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men.

Objective: To characterize sleep and the 24-hour profiles of cortisol, prolactin (PRL), and growth hormone (GH) secretion in mania. Methods: Blood was sampled at 15-minute intervals, and sleep was polygraphically recorded in eight unmedicated male patients with pure mania and the results compared with those from a group of 14 healthy age-matched controls. The circadian, sleep-related, and pulsatile hormonal variations were quantitatively characterized using specially designed computer algorithms. Results: The manic state was associated with alterations of corticotropic activity and circadian rhythmicity partially overlapping those previously observed in acute endogenous depression, consisting of an elevation of nocturnal cortisol levels and an early timing of the nadir of the circadian variation. Sleep onset was delayed and the sleep period was reduced. A trend for short rapid eye movement latencies was apparent in the adult patients. Both the amount and the temporal organization of PRL and GH secretion were normal. Conclusion: The manic state seems to be characterized by similar but less severe neuroendocrine and circadian abnormalities, compared with major depression.

The 24-Hour Profiles of Cortisol, Prolactin, and Growth Hormone Secretion in Mania

To delineate the contributions of genetic and environmental factors in the regulation of human prolactin (PRL) secretion, the 24-h profile of plasma PRL was obtained at 15-min intervals in 10 pairs of monozygotic and 10 pairs of dizygotic twins. Sleep was monitored polygraphically. PRL secretory rates were derived from plasma concentrations by deconvolution. Diurnal (24-h) variations were quantified by a regression curve to define nadir, acrophase, and amplitude. Pulses of PRL secretion were identified using a computerized algorithm. A procedure specifically developed for twin studies was used to partition the variance into genetic and environmental contributions. Significant genetic effects were identified for daytime PRL concentrations, rhythm amplitude, and overall wave-shape of the daily PRL profile. In contrast, environmental effects were dominant for mean concentrations during sleep, total secretory output during sleep, overall 24-h concentrations, and total 24-h secretion. However, when interindividual variations in sleep fragmentation were taken into account, the estimates of genetic variance for PRL concentrations and secretion during sleep approached statistical significance. Significant genetic influences were identified for slow-wave sleep (SWS). Because SWS is associated with increased nocturnal PRL secretion, it is possible that genetic effects on PRL secretion during sleep reflect genetic influences on SWS. In conclusion, genetic factors determine partially both the basal daytime concentrations of PRL and the temporal organization of PRL secretion over the 24-h cycle in normal young men.

Genetic and environmental influences on prolactin secretion during wake and during sleep.

The immunological detection of P-Glycoprotein (P-GP) and the functional release of Rhodamine 123 (R123) have been compared in a number of human and murine cancer cell lines, in chemo- and/or radiotherapy-resistant subclones, and in clinical specimens from patients. The chemoresistance level was established from the viability index (IC50) in the presence of doxorubicin. Cytocentrifuge preparations were immunostained with JSB-1 monoclonal antibody followed by the alkaline phosphatase anti-alkaline phosphatase technique. The strength of the reaction was quantified by a digital image analyser. The kinetic incorporation and release of Rhodamine 123 were evaluated by flow cytometry. The parent cell lines and radiotherapy resistant subclones showed a low IC50, were JSB-1 negative and retained R123 during the whole experiment, while the chemoresistant and radio-chemoresistant cell line mutants had a high IC50, were JSB-1 positive, and actively pumped the R123 out of the cells. Good correlations were obtained between the IC50, the digital image analysis, and flow cytometry. The kinetic profile of the R123 release allowed the distinction between typical and atypical multidrug resistance phenotypes. These findings were confirmed in clinical specimens from patients. We conclude that antigenic and functional studies are complementary and are useful in experimental and clinical approaches to multidrug resistance.

Comparative study of multidrug resistance evaluated by means of the quantitative immunohistochemical detection of P-glycoprotein and the functional release of rhodamine 123

Anne Van Onderbergen

Papers

Phase-shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men.

The 24-Hour Profiles of Cortisol, Prolactin, and Growth Hormone Secretion in Mania

Genetic and environmental influences on prolactin secretion during wake and during sleep.

Comparative study of multidrug resistance evaluated by means of the quantitative immunohistochemical detection of P-glycoprotein and the functional release of rhodamine 123