scholarly journals RFamide-Related Peptide Gene Is a Melatonin-Driven Photoperiodic Gene

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 902-912 ◽  
Author(s):  
Florent G. Revel ◽  
Michel Saboureau ◽  
Paul Pévet ◽  
Valérie Simonneaux ◽  
Jens D. Mikkelsen

In seasonal species, various physiological processes including reproduction are organized by photoperiod via melatonin, but the mechanisms of melatonin action are still unknown. In birds, the peptide gonadotropin-inhibiting hormone (GnIH) has been shown to have inhibitory effects on reproductive activity and displays seasonal changes of expression. Here we present evidence in mammals that the gene orthologous to GnIH, the RFamide-related peptide (RFRP) gene, expressed in the mediobasal hypothalamus, is strongly regulated by the length of the photoperiod, via melatonin. The level of RFRP mRNA and the number of RFRP-immunoreactive cell bodies were reduced in sexually quiescent Syrian and Siberian hamsters acclimated to short-day photoperiod (SD) compared with sexually active animals maintained under long-day photoperiod (LD). This was contrasted in the laboratory Wistar rat, a non-photoperiodic breeder, in which no evidence for RFRP photoperiodic modulation was seen. In Syrian hamsters, the reduction of RFRP expression in SD was independent from secondary changes in gonadal steroids. By contrast, the photoperiodic variation of RFRP expression was abolished in pinealectomized hamsters, and injections of LD hamsters with melatonin for 60 d provoked inhibition of RFRP expression down to SD levels, indicating that the regulation is dependent on melatonin. Altogether, these results demonstrate that in these hamster species, the RFRP neurons are photoperiodically modulated via a melatonin-dependent process. These observations raise questions on the role of RFRP as a general inhibitor of reproduction and evoke new perspectives for understanding how melatonin controls seasonal processes via hypothalamic targets.

2003 ◽  
Vol 285 (4) ◽  
pp. R873-R879 ◽  
Author(s):  
Gregory E. Demas ◽  
Timothy J. Bartness ◽  
Randy J. Nelson ◽  
Deborah L. Drazen

Siberian hamsters ( Phodopus sungorus) rely on photoperiod to coordinate seasonally appropriate changes in physiology, including immune function. Immunity is regulated, in part, by the sympathetic nervous system (SNS), although the precise role of the SNS in regulating photoperiodic changes in immunity remains unspecified. The goal of the present study was to examine the contributions of norepinephrine (NE), the predominant neurotransmitter of the SNS, to photoperiodic changes in lymphocyte proliferation. In experiment 1, animals were maintained in long [16:8-h light-dark cycle (16:8 LD)] or short days (8:16 LD) for 10 wk, and splenic NE content was determined. In experiment 2, in vitro splenocyte proliferation in response to mitogenic stimulation (concanavalin A) was assessed in spleen cell suspensions taken from long- or short-day hamsters in which varying concentrations of NE were added to the cultures. In experiment 3, splenocyte proliferation was examined in the presence of NE and selective α- and β-noradrenergic receptor antagonists (phenoxybenzamine and propranolol, respectively) in vitro. Short-day animals had increased splenic NE content compared with long-day animals. Long-day animals had higher proliferation compared with short-day animals independent of NE. NE (1 μM) further suppressed splenocyte proliferation in short but not long days. Last, NE-induced suppression of proliferation in short-day hamsters was blocked by propranolol but not phenoxybenzamine. The present results suggest that NE plays a role in photoperiodic changes in lymphocyte proliferation. Additionally, the data suggest that the effects of NE on proliferation are specific to activation of β-adrenergic receptors located on splenic tissue. Collectively, these results provide further support that photoperiodic changes in immunity are influenced by changes in SNS activity.


2011 ◽  
Vol 07 (01) ◽  
pp. 65
Author(s):  
Christopher D John ◽  
Julia C Buckingham ◽  
◽  

Glucocorticoids (GCs) are the end products of the hypothalamo–pituitary–adrenocortical axis (HPA) and, via activation of the ubiquitously expressed GC receptor, influence numerous physiological processes. GCs are also involved in the regulation of basal homeostasis as well as mediating adaptive responses to stress that act to restore homeostasis. This article discusses the various factors that are important in regulating plasma and intracellular GC concentrations and describes the genomic and non-genomic mechanisms used by GCs to influence cellular processes. We describe the concept of allostatic overload associated with chronic HPA activation and the subsequent development of tissue dysfunction and disease. While allostasis is associated with acute stress and a restoration of homeostasis, chronic stress is likely to induce allostatic overload owing to the sustained activation of adaptive processes. Increased wear and tear in GC-sensitive tissues can eventually lead to tissue dysfunction and disease. Chronic elevations in GCs can also induce dysfunction or disease associated with decreased tissue function owing to the prolonged inhibitory effects of GCs or the redistribution of metabolic resource away from physiological systems not involved in restoring homeostasis. Numerous endocrine-related disorders are associated with aberrant GC levels and in terms of pathophysiology may be linked with chronic tissue-specific alterations in GC actions.


2010 ◽  
Vol 277 (1695) ◽  
pp. 2867-2874 ◽  
Author(s):  
Matthew P. Butler ◽  
Kevin W. Turner ◽  
Jin Ho Park ◽  
Elanor E. Schoomer ◽  
Irving Zucker ◽  
...  

The seasonal reproductive cycle of photoperiodic rodents is conceptualized as a series of discrete melatonin-dependent neuroendocrine transitions. Least understood is the springtime restoration of responsiveness to winter-like melatonin signals (breaking of refractoriness) that enables animals to once again respond appropriately to winter photoperiods the following year. This has been posited to require many weeks of long days based on studies employing static photoperiods instead of the annual pattern of continually changing photoperiods under which these mechanisms evolved. Maintaining Siberian hamsters under simulated natural photoperiods, we demonstrate that winter refractoriness is broken within six weeks after the spring equinox. We then test whether a history of natural photoperiod exposure can eliminate the requirement for long-day melatonin signalling. Hamsters pinealectomized at the spring equinox and challenged 10 weeks later with winter melatonin infusions exhibited gonadal regression, indicating that refractoriness was broken. A photostimulatory effect on body weight is first observed in the last four weeks of winter. Thus, the seasonal transition to the summer photosensitive phenotype is triggered prior to the equinox without exposure to long days and is thereafter melatonin-independent. Distinctions between photoperiodic and circannual seasonal organization erode with the incorporation in the laboratory of ecologically relevant day length conditions.


1991 ◽  
Vol 260 (1) ◽  
pp. R102-R112 ◽  
Author(s):  
T. J. Bartness ◽  
B. D. Goldman ◽  
E. L. Bittman

The role of the suprachiasmatic nuclei (SCN) in the response to short-day melatonin (MEL) signals was examined in long-day-housed pinealectomized (PINX) Siberian hamsters. Five- or ten-hour MEL infusions that mimicked the peak nocturnal durations of serum MEL levels in long or short days, respectively, or control saline infusions were given for 5 wk. Half the hamsters in each infusion group also received bilateral electrolytic SCN lesions. The 10-h MEL infusions reduced testes weight, body and fat pad weights, and serum prolactin (PRL) and follicle-stimulating hormone (FSH) concentrations in unoperated controls. These short-day-type effects were blocked by SCN lesions, which often produced hyperprolactinemia. Circadian rhythms of locomotor activity were disrupted or sparse in hamsters with lesions in or near the SCN. In a second experiment, 5 wk of long-day-like, short-duration (5-h) MEL infusions were administered to hamsters that had been PINX after 8 wk of short-day exposure. Control hamsters given 5-h MEL infusions, but not 10-h MEL or saline infusions, exhibited testicular growth and increased serum PRL levels. Hamsters with SCN lesions showed similar responses, regardless of the duration or type of infusion. Although the blockade of 10-h MEL infusion-induced testicular regression by SCN lesions in experiment 1 may have been due to stimulation of the testes by PRL, it is unlikely that the hyperprolactinemia accounted for the ability of SCN lesions to block effects of 10-h MEL infusions on fat pad and body weights. Therefore, the SCN and/or neighboring structures may participate in the response to short-day MEL signals in Siberian hamsters.


2010 ◽  
Vol 7 (1) ◽  
pp. 47
Author(s):  
Christopher D John ◽  
Julia C Buckingham ◽  
◽  

Glucocorticoids (GCs) are the end products of the hypothalamo–pituitary–adrenocortical axis (HPA) and, via activation of the ubiquitously expressed GC receptor, influence numerous physiological processes. GCs are also involved in the regulation of basal homeostasis as well as mediating adaptive responses to stress that act to restore homeostasis. This article discusses the various factors that are important in regulating plasma and intracellular GC concentrations and describes the genomic and non-genomic mechanisms used by GCs to influence cellular processes. We describe the concept of allostatic overload associated with chronic HPA activation and the subsequent development of tissue dysfunction and disease. While allostasis is associated with acute stress and a restoration of homeostasis, chronic stress is likely to induce allostatic overload owing to the sustained activation of adaptive processes. Increased wear and tear in GC-sensitive tissues can eventually lead to tissue dysfunction and disease. Chronic elevations in GCs can also induce dysfunction or disease associated with decreased tissue function owing to the prolonged inhibitory effects of GCs or the redistribution of metabolic resource away from physiological systems not involved in restoring homeostasis. Numerous endocrine-related disorders are associated with aberrant GC levels and in terms of pathophysiology may be linked with chronic tissue-specific alterations in GC actions.


2010 ◽  
Vol 22 (6) ◽  
pp. 564-575 ◽  
Author(s):  
P. H. Jethwa ◽  
A. Warner ◽  
M. J. Fowler ◽  
M. Murphy ◽  
M. W. De Backer ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 639
Author(s):  
Domenico Ribatti ◽  
Francesco Pezzella

Angiogenesis is a crucial event in the physiological processes of embryogenesis and wound healing. During malignant transformation, dysregulation of angiogenesis leads to the formation of a vascular network of tumor-associated capillaries promoting survival and proliferation of the tumor cells. Starting with the hypothesis formulated by Judah Folkman that tumor growth is angiogenesis-dependent, this area of research has a solid scientific foundation and inhibition of angiogenesis is a major area of therapeutic development for the treatment of cancer. Over this period numerous authors published data of vascularization of tumors, which attributed the cause of neo-vascularization to various factors including inflammation, release of angiogenic cytokines, vasodilatation, and increased tumor metabolism. More recently, it has been demonstrated that tumor vasculature is not necessarily derived by endothelial cell proliferation and sprouting of new capillaries, but alternative vascularization mechanisms have been described, namely vascular co-option and vasculogenic mimicry. In this article, we have analyzed the mechanisms involved in tumor vascularization in association with classical angiogenesis, including post-natal vasculogenesis, intussusceptive microvascular growth, vascular co-option, and vasculogenic mimicry. We have also discussed the role of these alternative mechanism in resistance to anti-angiogenic therapy and potential therapeutic approaches to overcome resistance.


2021 ◽  
Vol 22 (11) ◽  
pp. 5918
Author(s):  
Paweł Kordowitzki ◽  
Gabriela Sokołowska ◽  
Marta Wasielak-Politowska ◽  
Agnieszka Skowronska ◽  
Mariusz T. Skowronski

The oocyte is the major determinant of embryo developmental competence in all mammalian species. Although fundamental advances have been generated in the field of reproductive medicine and assisted reproductive technologies in the past three decades, researchers and clinicians are still trying to elucidate molecular factors and pathways, which could be pivotal for the oocyte’s developmental competence. The cell-to-cell and cell-to-matrix communications are crucial not only for oocytes but also for multicellular organisms in general. This latter mentioned communication is among others possibly due to the Connexin and Pannexin families of large-pore forming channels. Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility. Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells. Herein, the role of Pannexins and Connexins for the processes of oogenesis, folliculogenesis, oocyte maturation and fertilization will be discussed and, at the end of this review, Pannexin and Connexin related pathologies and their impact on the developmental competence of oocytes will be provided.


2021 ◽  
Vol 120 ◽  
pp. 104065
Author(s):  
A. Urbański ◽  
N. Konopińska ◽  
J. Lubawy ◽  
K. Walkowiak-Nowicka ◽  
P. Marciniak ◽  
...  

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