Neuropeptides in the Gonads: From Evolution to Pharmacology

Vertebrate gonads are the sites of synthesis and binding of many peptides that were initially classified as neuropeptides. These gonadal neuropeptide systems are neither well understood in isolation, nor in their interactions with other neuropeptide systems. Further, our knowledge of the control of these gonadal neuropeptides by peripheral hormones that bind to the gonads, and which themselves are under regulation by true neuropeptide systems from the hypothalamus, is relatively meager. This review discusses the existence of a variety of neuropeptides and their receptors which have been discovered in vertebrate gonads, and the possible way in which such systems could have evolved. We then focus on two key neuropeptides for regulation of the hypothalamo-pituitary-gonadal axis: gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone (GnIH). Comparative studies have provided us with a degree of understanding as to how a gonadal GnRH system might have evolved, and they have been responsible for the discovery of GnIH and its gonadal counterpart. We attempt to highlight what is known about these two key gonadal neuropeptides, how their actions differ from their hypothalamic counterparts, and how we might learn from comparative studies of them and other gonadal neuropeptides in terms of pharmacology, reproductive physiology and evolutionary biology

The Role of RFamide-Related Peptide-3 in Age-Related Reproductive Decline in Female Rats.

Reproductive senescence, the point in time when females cease to show estrous cyclicity, is associated with endocrine changes in the hypothalamus, pituitary, and gonads. However, the mechanisms triggering this transition are not well understood. To gain a better understanding of the top-down control of the transition from reproductive competence to a state of reproductive senescence, we investigated middle-aged female rats exhibiting varying degrees of reproductive decline, including individuals with normal cycles, irregular cycles, and complete cessation of cycles. We identified hormonal changes in the brain that manifest before ovarian cycles exhibit any deterioration. We found that females exhibit an increase in RFamide-related peptide-3 (RFRP3) mRNA expression in the hypothalamus in middle age prior to changes in estrous cycle length. This increase is transient and followed by subsequent decreases in kisspeptin (KiSS1) and gonadotropin-releasing hormone (GnRH) mRNA expression. Expression of RFRP3 and its receptor also increased locally in the ovaries with advancing age. While it is well known that aging is associated with decreased GnRH release and downstream disruption of the hypothalamic-pituitary-gonadal (HPG) axis, herein, we provide evidence that reproductive senescence is likely triggered by alterations in a network of regulatory neuropeptides upstream of the GnRH system

Neurosecretory Protein GL Induces Fat Accumulation in Chicks.

We recently found a previously unidentified cDNA in chicken hypothalamus which encodes the precursor for neurosecretory protein GL (NPGL). A previous study showed that intracerebroventricular (i.c.v.) infusion of NPGL caused body mass gain in chicks. However, it was not clear which part(s) of the body gained mass. In the present study, we investigated which tissues increased in mass after chronic i.c.v. infusion of NPGL in chicks. We found that NPGL increased the masses of the liver, abdominal fat, and subcutaneous fat, while NPGL did not affect the masses of muscles, including pectoralis major, pectoralis minor, and biceps femoris. Oil Red O staining revealed that fat deposition had occurred in the liver. In addition, the size of the lipid droplets in the abdominal fat increased. Furthermore, we found an upregulation of lipogenesis and downregulation of lipolysis in the abdominal fat, but not in the liver. These results indicate that NPGL is involved in fat storage in chicks

Neurosecretory protein GL stimulates food intake, de novo lipogenesis, and onset of obesity.

Mechanisms underlying the central regulation of food intake and fat accumulation are not fully understood. We found that neurosecretory protein GL (NPGL), a newly-identified neuropeptide, increased food intake and white adipose tissue (WAT) in rats. NPGL-precursor gene overexpression in the hypothalamus caused increases in food intake, WAT, body mass, and circulating insulin when fed a high calorie diet. Intracerebroventricular administration of NPGL induced de novo lipogenesis in WAT, increased insulin, and it selectively induced carbohydrate intake. Neutralizing antibody administration decreased the size of lipid droplets in WAT. Npgl mRNA expression was upregulated by fasting and low insulin levels. Additionally, NPGL-producing cells were responsive to insulin. These results point to NPGL as a novel neuronal regulator that drives food intake and fat deposition through de novo lipogenesis and acts to maintain steady-state fat level in concert with insulin. Dysregulation of NPGL may be a root cause of obesity

Anticipating Spring: Wild Populations of Great Tits (Parus major) Differ in Expression of Key Genes for Photoperiodic Time Measurement

Measuring day length is critical for timing annual changes in physiology and behavior in many species. Recently, rapid changes in several photoperiodically-controlled genes following exposure to a single long day have been described. Components of this ‘first day release’ model have so far only been tested in highly domesticated species: quail, sheep, goats and rodents. Because artificial selection accompanying domestication acts on genes related to photoperiodicity, we must also study this phenomenon in wild organisms for it to be accepted as universal. In a songbird, the great tit (Parus major), we tested whether a) these genes are involved in photoperiodic time measurement (PTM) in a wild species, and b) whether predictable species and population differences in expression patterns exist. Using quantitative RT-PCR, we compared gene expression after a single long day in male great tits from Sweden (57°42′N) with that from a German (47°43′N) population. Hypothalamic gene expression key for PTM changed only in the northern population, and occurred earlier after dawn during the single long day than demonstrated in quail; however, gonadotropins (secretion and synthesis) were stimulated in both populations, albeit with different timing. Our data are the first to show acute changes in gene expression in response to photostimulation in any wild species not selected for study of photoperiodism. The pronounced differences in gene expression in response to a single long day between two populations raise exciting new questions about potential environmental selection on photoperiodic cue sensitivity

RNA interference of gonadotropin-inhibitory hormone gene induces arousal in songbirds.

Gonadotropin-inhibitory hormone (GnIH) was originally identified in quail as a hypothalamic neuropeptide inhibitor of pituitary gonadotropin synthesis and release. However, GnIH neuronal fibers do not only terminate in the median eminence to control anterior pituitary function but also extend widely in the brain, suggesting it has multiple roles in the regulation of behavior. To identify the role of GnIH neurons in the regulation of behavior, we investigated the effect of RNA interference (RNAi) of the GnIH gene on the behavior of white-crowned sparrows, a highly social songbird species. Administration of small interfering RNA against GnIH precursor mRNA into the third ventricle of male and female birds reduced resting time, spontaneous production of complex vocalizations, and stimulated brief agonistic vocalizations. GnIH RNAi further enhanced song production of short duration in male birds when they were challenged by playbacks of novel male songs. These behaviors resembled those of breeding birds during territorial defense. The overall results suggest that GnIH gene silencing induces arousal. In addition, the activities of male and female birds were negatively correlated with GnIH mRNA expression in the paraventricular nucleus. Density of GnIH neuronal fibers in the ventral tegmental area was decreased by GnIH RNAi treatment in female birds, and the number of gonadotropin-releasing hormone neurons that received close appositions of GnIH neuronal fiber terminals was negatively correlated with the activity of male birds. In summary, GnIH may decrease arousal level resulting in the inhibition of specific motivated behavior such as in reproductive contexts

A numerical investigation of wave-supported gravity flow during cold fronts over the Atchafalaya Shelf

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 125(9), (2020): e2019JC015269, doi:10.1029/2019JC015269Wave‐supported fluid mud (WSFM) plays an important role in sediment downslope transport on the continental shelves. In this study, we incorporated WSFM processes in the wave boundary layer (WBL) into the Community Sediment Transport Modeling System (CSTMS) on the platform of the Coupled Ocean‐Atmosphere‐Wave‐and‐Sediment Transport modeling system (COAWST). The WSFM module was introduced between the bottommost water layer and top sediment layer, which accounted for the key sediment exchange processes (e.g., resuspension, vertical settling, diffusion, and horizontal advection) at the water‐WBL and WBL‐sediment bed boundaries. To test its robustness, we adapted the updated model (CSTMS + WBL) to the Atchafalaya shelf in the northern Gulf of Mexico and successfully reproduced the sediment dynamics in March 2008, when active WSFM processes were reported. Compared with original CSTMS results, including WSFM module weakened the overall intensity of sediment resuspension, and the CSTMS + WBL model simulated a lutocline between the WBL and overlying water due to the formation of WSFM. Downslope WSFM transport resulted in offshore deposition (>4 cm), which greatly changed the net erosion/deposition pattern on the inner shelf off the Chenier Plain. WSFM flux was comparable with suspended sediment flux (SSF) off the Atchafalaya Bay, and it peaked along the Chenier Plain coast where wave activities were strong and the bathymetric slope was steep. The influence of fluvial sediment supply on sediment dynamics was limited in the Atchafalaya Bay. Sensitivity tests of free settling, flocculation, and hindered settling effects suggested that sediments were transported further offshore due to reduced settling velocity in the WBL once fluid mud was formed. Although sediment concentration in the WBL was sensitive to surface sediment critical shear stress, cohesive bed behavior was less important in WSFM dynamics when compared with strong hydrodynamic during cold fronts.Research support provided through NSF CyberSEES (Award CCF‐1856359), NASA (Award NNH17ZHA002C), Louisiana Board of Regents (award number NASA/LEQSF(2018‐20)‐Phase3‐11), Bureau of Ocean Energy Management (Cooperative Agreement Award M20AC00007), NSF Coastal SEES (Award EAR‐1427389 ), NSF (Award OCE‐20203676), and LSU Foundation Billy and Ann Harrison Endowment for Sedimentary Geology.2021-02-1

Pengkomputeran awam perkasa pembelajaran

Berikutan perkembangan teknologi maklumat semasa, cara kita menyelesaikan masalah dalam setiap aspek kehidupan turut berubah. Perisian komputer banyak mempengaruhi cara kita mencari maklumat, mengambil keputusan, membuat penilaian dan perancangan. Sistem maklumat ini meningkatkan keberkesanan dalam sistem penyampaian dan pembelajaran