Photoperiod–Testicular–Immune Interaction in a Seasonal Breeder Indian Palm Squirrel Funambulus pennanti During the Reproductively Inactive and Active Phases
TL;DR: The peripheral melatonin level of those squirrels reflected the photoperiodic signal perceived by squirrels for immunomodulation and gonadal function, suggesting that immune system and Gonadal function might have coevolved.
Abstract: The differential effect of long (LD; 16 : 8 h light/dark), short (SD; 10 : 14 h light/dark) and natural day length (NDL; 12 : 12 h light/dark) during the reproductively inactive (RIP) and active (RAP) phases was assessed in relation to immunity and reproductive function of a tropical rodent Funambulus pennanti. They presented high immunity and low testicular activity during RIP and an opposite during RAP. SD increased spleen and thymus weight, leukocyte and lymphocyte counts, cell mediated immunity [i.e. blastogenic response in terms of percentage stimulation ratio of splenocytes and thymocytes (when challenged with concanavalin A)] and delayed type hypersensitivity to oxazolone. SD during RIP increased the above mentioned parameters and reduced testes weight compared to NDL groups. During RAP, LD reduced all the immunological parameters when compared with NDL and SD experiencing groups of RIP and RAP phases. The LD group reduced the immunological parameters compared to RAP, suggesting that LD had always an inhibitory effect on immune status being independent of reproductive phases. The intensity of the stimulatory effects of SD and inhibitory effects of LD during both reproductive phases was significantly different. We exposed another set of squirrels to the above photoperiodic schedule for prolonged period (30 weeks) during RAP. A clear testicular refractoriness followed by immunorefractoriness was observed in the group experiencing SD and LD for 30 weeks. The photorefractoriness presented by the testes was inversely related to the immunorefractoriness. The peripheral melatonin level of those squirrels reflected the photoperiodic signal perceived by squirrels for immunomodulation and gonadal function, suggesting that immune system and gonadal function might have coevolved.
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TL;DR: It may be suggested that a physiological cross talk exist between Mel and GR which is of high adaptive significance in wild animals for balancing the immunity during ecologically stressful conditions.
43 citations
Cites background or methods from "Photoperiod–Testicular–Immune Inter..."
...The DTH response was expressed as change in percent thickness and was measured by comparing differences between oxazolone treated and vehicle treated ear pinna [3,29]....
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...Melatonin on the contrary is known to play an important role in immunomodulation by rescuing the immune cells from the immunocompromising effects of environmental stressors which ultimately leads to elevation of plasma corticosterone level [3,21,35,36]....
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TL;DR: Differential hormonal level of melatonin and gonadal hormones during reproductively active and inactive phase and its direct relation with melatonin receptor expression dynamics in lymphoid organs could be responsible for seasonal adjustment of immunity and reproduction.
Abstract: Photoperiodic regulation of melatonin receptor types on target tissues, such as lymphatic organs, has never been explored for any seasonal breeder. In the present study, we accessed the high affinity membrane melatonin receptors MT1 and MT2 expression dynamics in lymphoid organs (i.e., spleen and thymus) of a seasonally breeding rodent Funambulus pennanti during two major reproductive phases (i.e., active and inactive), when the internal hormonal (melatonin and gonadal steroid) as well as the ecological conditions were entirely different. Photoperiod regulates circulatory melatonin level; hence, we noted the effect of different photoperiodic regimes (long; 16L:8D and short; 10L:14D photoperiod) equivalent to summer and winter daylength on membrane melatonin receptor MT1 and MT2 expression in spleen and thymus. We have correlated the melatonin receptor expression with two major hormones varying seasonally (i.e., melatonin and testosterone) also being responsible for modulation of immunity of a seasonal breeder. Differential immunoreactivity of MT1 and MT2 receptor in spleen and thymus of F. pennanti suggests an involvement of both the receptor types in signal transduction of photoperiod for seasonal immunomodulation, because in the tropical zone, a slight difference (1:45–2 h) in daylength may change reproductive physiology and immunity of animals for adaptation. Our above suggestion receives strong support from the experiment of photoperiodic exposure on MT1 and MT2 expression at the translational level, where long daylength decreased the circulatory melatonin level and melatonin receptor expression in both lymphatic tissues. On the other hand, under short daylength, expression of MT1 and MT2 receptor increased in both spleen and thymus along with concomitant increase in circulatory melatonin level. Differential hormonal level of melatonin and gonadal hormones during reproductively active and inactive phase and its direct relation with melatonin receptor expression dynamics in lymphoid organs could be
38 citations
Cites background from "Photoperiod–Testicular–Immune Inter..."
...…F. pennanti is a photoresponsive tropical seasonal breeder presenting two different major (active and inactive) reproductive phases during the year (Haldar et al., 2001) to adjust its various physiological functions along with immunity and reproduction (Ahmad & Haldar, 2009; Haldar & Saxena, 1988)....
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...…in lymphoid organs of any tropical seasonal breeder, in general, and especially the Indian palm squirrel, where not only the spleen but the thymus plays an important role in maintaining immune function according to the seasons (Ahmad & Haldar, 2009; Haldar & Singh, 2001; Haldar et al., 2001)....
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...Androgens can be important mediators of seasonal adjustment of immunity with reproduction in a seasonal breeder (Ahmad & Haldar, 2009; Nelson & Demas, 1996; Rai & Haldar, 2003)....
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...The spleen and thymus both showed variation in their response as judged by their mass and the blastogenic response of splenocytes and thymocytes during the reproductively active and inactive phases (Ahmad & Haldar, 2009)....
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...A trade-off relationship between melatonin and testosterone was reported for Indian palm squirrels (Ahmad & Haldar, 2009), though both hormones act in concert to provide the best possible and optimal immune condition for the survival of squirrels in relation to reproduction under the different…...
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TL;DR: A clear‐cut trade‐off relation between mt1R and AR expression is suggested that might be acting as an important mediator in seasonal adjustment of immune function in tropical rodents.
Abstract: An inverse relation exists between melatonin and androgen in most of the seasonally breeding rodents, but the regulation of their receptors in modulation of immune function has never been reported. The present study accessed the expression pattern of melatonin receptor types (mt1R & mt2R), immune parameters (lymphoid organs weight, leucocyte count, delayed type hypersensitivity and lymphocyte proliferation) in spleen and thymus whereas androgen receptor (AR) expression in thymus of Funambulus pennanti during reproductively active phase. In-vivo melatonin treatment (Mel) and castration (Cx) significantly increased mt1R expression, immune parameters in spleen and thymus but decreased AR expression in thymus only when compared with sham control (Con) squirrels as AR expression was not observed in spleen. Mel alone or in combination with testosterone (T) to Cx squirrels significantly increased mt1R expression, immune parameters in spleen and thymus but decreased AR expression in thymus. T alone in Cx squirrels significantly decreased mt1R expression, immune parameters in spleen and thymus but increased thymic AR expression significantly. In-vitro thymocyte culture supported our in-vivo findings. Mel significantly increased mt1R expression, lymphocyte proliferation, IL-2 secretion but decreased AR expression. T alone significantly decreased aforementioned three parameters but increased AR expression. Combined treatment of Mel and T bring back all parameters to control level. Though we found high mt2R expression, but no significant change has been observed. Thus, present study suggests a clear-cut trade-off relation between mt1R and AR expression that might be acting as an important mediator in seasonal adjustment of immune function in tropical rodents.
30 citations
TL;DR: It is suggested that photoperiod via regulating circulatory and local melatonin level as well as MT1R expression in testes fine tunes the steroidogenesis and thereby, the reproductive status of male golden hamster.
Abstract: Photoperiodic modulation of melatonin membrane receptor (MT1R) expression in testis has never been reported for any seasonal breeder. Thus, the aim of the present study was to investigate the expression dynamics of MT1R in testis and its interaction with testicular steroidogenesis in a long-day breeder, Mesocricetus auratus . Hamsters were exposed to different photoperiodic conditions i.e. critical- (CP; 12.5L:11.5D); short-day- (SD; 8L:16D) and long-day- (LD; 16L:8D) for 10 weeks wherein testicular steroidogenesis, local melatonin synthesis and the expression of MT1R were analyzed. SD induced melatonin suppressed testicular steroidogenesis as evident from regressed testicular histoarchitecture, decreased expression of AR, StAR, LH-R, P 450 SCC and enzyme activities of 3β- and 17β-HSD. Differential photoperiodic regulation of MT1R expression in testis suggests its involvement in photoperiodic signal transduction for seasonal adjustment of reproduction. Increased S-NAT (Serotonin N-acetyl transferase) activity and local testicular melatonin under SD condition suggest an inhibitory effect of the local melatonergic system on testicular steroidogenesis. Completely opposite responses were recorded for all the parameters analyzed when hamsters were exposed to CP or LD conditions. In conclusion, we may suggest that photoperiod via regulating circulatory and local melatonin level as well as MT1R expression in testes fine tunes the steroidogenesis and thereby, the reproductive status of male golden hamster.
30 citations
TL;DR: The results suggest that melatonin may mediate GL-induced T-lymphocyte proliferation via the Mel1b and Mel1c receptors but not via theMel1a receptor.
Abstract: A total of 360 post-hatching day 0 (P0) Arbor Acre male broilers, including intact, sham operation and pinealectomy groups, were exposed to white light (WL), red light (RL), green light (GL) and blue light (BL) from a light-emitting diode (LED) system until for P14. We studied the effects of melatonin and its receptors on monochromatic light-induced T-lymphocyte proliferation in the thymus of broilers. The density of proliferating cell nuclear antigen (PCNA) cells and the proliferation of T-lymphocytes in response to Concanavalin A (ConA) in GL significantly increased both in vivo and in vitro (from 9.57% to 32.03% and from 34.30% to 50.53%, respectively) compared with other lights (p<0.005) and was strongly correlated with melatonin levels in plasma (p<0.005). Pinealectomy reduced the levels of circulatory melatonin and the proliferation of T-lymphocytes and eliminated the differences between GL and other lights (p<0.005). However, exogenous melatonin (10(-9)M) significantly increased the proliferative activity of T-lymphocyte by 9.64% (p=0.002). In addition, GL significantly increased mRNA expression levels of Mel1a, Mel1b and Mel1c receptors from 21.09% to 32.57%, and protein expression levels from 24.43% to 42.92% compared with RL (p<0.05). However, these effects were blocked after pinealectomy. Furthermore, 4P-PDOT (a selective Mel1b antagonist) and prazosin (a selective Mel1c antagonist) attenuated GL-induced T-lymphocyte proliferation in response to ConA (p=0.000). Luzindole (a nonselective Mel1a/Mel1b antagonist), however, did not induce these effects (p=0.334). These results suggest that melatonin may mediate GL-induced T-lymphocyte proliferation via the Mel1b and Mel1c receptors but not via the Mel1a receptor.
25 citations
References
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TL;DR: Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities, and its sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients.
Abstract: Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune-enhancing and oncostatic properties. Its 'chronobiotic' properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an 'internal sleep facilitator' promotes sleep, and melatonin's sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin's role as a 'photoperiodic molecule' in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body's physiological functions.
842 citations
Book•
31 Dec 1994
TL;DR: The pineal in human physiology and pathology and the role of the pineal gland and melatonin in circadian rhythms are studied to determine its therapeutic potential and significance to human health.
Abstract: Foreword. Melatonin and the mammalian pineal gland. Structure of the pineal gland. Biochemistry of the pineal. Light-dark control of melatonin synthesis. Physiology of the pineal: role in photoperiodic seasonal functions. Role of the pineal gland and melatonin in circadian rhythms. The pineal in human physiology and pathology. Effects of melatonin: therapeutic potential and significance to human health. Target sites and mechanism of action of melatonin. Index.
747 citations
TL;DR: A precipitous drop in serum concentrations of melatonin resulted when ewes experiencing peak melatonin concentrations were exposed to light and returned to peak levels when the lights were turned off 3.5 h later.
Abstract: A specific and sensitive double-antibody radioimmunoassay for melatonin (N-acetyl-5-methoxytryptamine) has been developed utilizing rabbit antisera to a bovine serum albumin conjugate of N-succinyl-5-methoxytryptamine and utilizing N-3-(4-hydroxyphenl)-propionyl-5-methoxytryptamine for radioiodination. The least detectable concentration of melatonin standard was 10 pmolar (2.3 pg/tube) with 50% inhibition resultinhibition curves obtained with increasing quantities of melatonin or increasing quantities of chloroform extracts of ovine sera were parallel. The immunoreactivity found in ovine sera c-migrated with [3H]melatonin on silica gel G when developed with chloroform:methanol (9:1). N-Acetylserotonin, 5-methoxytryptamine, serotonin, tryptophan, 6-hydroxymelatonin, 6-methoxytetrahydroharmalan, and several other indole and beta-carboline compounds do not influence the estimation of melatonin in the radioimmunoassay. Concentrations of melatonin could be accurately determined when 31 to 1000 pg were added to 1 ml ovine serum. Serum samples with melatonin concentrations of 1000 pg/ml, 500 pg/ml and 75 pg/ml had intra-assay coefficients of variation of 9.1%, 8.6%, and 17.4%, respectively. The respective inter-assay coefficients of variation were 22.7%, 18.1%, and 37.1%. Ewes exposed to a 12 h light: 12 h dark lighting regimen demonstrated a circadian rhythm in serum concentrations of melatonin. Concentrations ranged from 10-30 pg/ml during periods of light to 100-300 pg/ml during periods of dark. During exposure to continuous light, the circadian rhythm was abolished and concentrations of melatonin were maintained at 10-50 pg/ml. When exposed to conditions of continuous dark the circadian rhythm persisted. A precipitous drop in serum concentrations of melatonin resulted when ewes experiencing peak melatonin concentrations were exposed to light. Concentrations returned to peak levels when the lights were turned off 3.5 h later.
661 citations
TL;DR: The results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents and show that hormones released during an acute stress response may help prepare the immune system for potential challenges for which stress perception by the brain may serve as an early warning signal.
Abstract: Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated immune responses that, depending on the antigen, mediate beneficial (e.g., resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis and autoimmunity) aspects of immune function. Contrary to the idea that stress suppresses immunity, we have reported that short-duration stressors significantly enhance skin DTH and that a stress-induced trafficking of leukocytes to the skin may mediate this immunoenhancement. Here, we identify the hormonal mediators of a stress-induced enhancement of skin immunity. Adrenalectomy, which eliminates the glucocorticoid and epinephrine stress response, eliminated the stress-induced enhancement of skin DTH. Low-dose corticosterone or epinephrine administration significantly enhanced skin DTH and produced a significant increase in the number of T cells in lymph nodes draining the site of the DTH reaction. In contrast, high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone administration significantly suppressed skin DTH. These results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents. These results also show that hormones released during an acute stress response may help prepare the immune system for potential challenges (e.g., wounding or infection) for which stress perception by the brain may serve as an early warning signal.
649 citations
TL;DR: It is the collective view that the TIP has played, and will continue to play, a pivotal role in elucidation of the function of MEL in the photoperiodic control of seasonal mammalian responses and that the duration of the MEL signal is the critical parameter of the nocturnal secretion profile of the hormone for the phot operable control of several seasonally adaptive responses in mammalian species as diverse as hamsters and sheep.
Abstract: This review summarizes the evidence showing that the duration of the nocturnal secretory profile of pineal melatonin (MEL) is critical for eliciting seasonally appropriate reproductive physiological and behavioral responses in mammals. We review experiments using the timed infusion paradigm (TIP) to deliver MEL either systemically or centrally to pinealectomized hamsters and sheep. In this paradigm, MEL is infused, usually once daily, for a specific number of hours and at a predetermined time of day. This experimental strategy tests most directly those features of the MEL signal that are necessary to trigger photoperiodic responses. The data suggest that the duration of the MEL stimulation is the critical feature of the MEL signal for both inhibitory and stimulatory effects of the hormone on the photoperiodic control of reproductive development in juvenile Siberian hamsters, and for the photoperiodic control of reproductive and metabolic responses in adult Siberian and Syrian hamsters and sheep. The use of the TIP reveals the importance of the frequency of the signal presentation of MEL and suggests the importance of a period of low-to-absent circulating concentrations of the hormone. The TIP also reveals that the characteristics of the MEL signal that regulate male sexual behavior are similar to those that are critical for reproductive and metabolic responses in Syrian hamsters. We summarize the locations of possible functional MEL target sites identified by combining the TIP with traditional brain lesion techniques. Evidence from such studies suggests that the integrity of the suprachiasmatic nucleus (SCN) region in Siberian hamsters and the anterior hypothalamus in Syrian hamsters is necessary for the response to short-day MEL signals. The TIP has been used to deliver MEL to putative target sites for the hormone in the brain of juvenile and adult Siberian hamsters. The results of these preliminary experiments suggest that the regions of specific MEL binding in this species, especially the SCN, are effective sites where MEL may stimulate short-day-type responses. In contrast, results from intracranial application of MEL in sheep suggest the medial basal hypothalamus as a critical site of action. Finally, we also discuss potential applications of the TIP for identification of brain MEL target sites, understanding of other photoperiodic phenomena and responses, and resolution of the cellular/molecular basis underlying the reception and interpretation of MEL signals.(ABSTRACT TRUNCATED AT 400 WORDS)
527 citations