While the number of studies providing evidence of actuarial senescence is increasing, and covers a wide range of taxa, the process of reproductive senescence remains poorly understood. In fact, quite high reproductive output until the last years of life has been reported in several vertebrate species, so that whether or not reproductive senescence is widespread remains unknown. We compared age-specific changes of reproductive parameters between two closely related species of long-lived seabirds: the small-sized snow petrel Pagodroma nivea, and the medium-sized southern fulmar Fulmarus glacialoides. Both are sympatric in Antarctica. We used an exceptional dataset collected over more than 40 years to assess age-specific variations of both breeding probability and breeding success. We found contrasted age-specific reproductive patterns between the two species. Reproductive senescence clearly occurred from 21 years of age onwards in the southern fulmar, in both breeding probability and success, whereas we did not report any decline in the breeding success of the snow petrel, although a very late decrease in the proportion of breeders occurred at 34 years. Such a contrasted age-specific reproductive pattern was rather unexpected. Differences in life history including size or migratory behaviour are the most likely candidates to account for the difference we reported in reproductive senescence between these sympatric seabird species.
vertebrates; life history; senescence; breeding success; age; Antarctic seabirds
Among vertebrates, the sense of smell is mediated by olfactory receptors (ORs) expressed in sensory neurons within the olfactory epithelium. Comparative genomic studies suggest that the olfactory acuity of mammalian species correlates positively with both the total number and the proportion of functional OR genes encoded in their genomes. In contrast to mammals, avian olfaction is poorly understood, with birds widely regarded as relying primarily on visual and auditory inputs. Here, we show that in nine bird species from seven orders (blue tit, Cyanistes caeruleus; black coucal, Centropus grillii; brown kiwi, Apteryx australis; canary, Serinus canaria; galah, Eolophus roseicapillus; red jungle fowl, Gallus gallus; kakapo, Strigops habroptilus; mallard, Anas platyrhynchos; snow petrel, Pagodroma nivea), the majority of amplified OR sequences are predicted to be from potentially functional genes. This finding is somewhat surprising as one previous report suggested that the majority of OR genes in an avian (red jungle fowl) genomic sequence are non-functional pseudogenes. We also show that it is not the estimated proportion of potentially functional OR genes, but rather the estimated total number of OR genes that correlates positively with relative olfactory bulb size, an anatomical correlate of olfactory capability. We further demonstrate that all the nine bird genomes examined encode OR genes belonging to a large gene clade, termed γ-c, the expansion of which appears to be a shared characteristic of class Aves. In summary, our findings suggest that olfaction in birds may be a more important sense than generally believed.
olfaction; bird; olfactory bulb; pseudogene; nocturnality; ecological adaptation
The structure, functioning and dynamics of polar marine ecosystems are strongly influenced by the extent of sea ice. Ice algae and pelagic phytoplankton represent the primary sources of nutrition for higher trophic-level organisms in seasonally ice-covered areas, but their relative contributions to polar marine consumers remain largely unexplored. Here, we investigated the potential of diatom-specific lipid markers and highly branched isoprenoids (HBIs) for estimating the importance of these two carbon pools in an Antarctic pelagic ecosystem. Using GC-MS analysis, we studied HBI biomarkers in key marine species over three years in Adélie Land, Antarctica: euphausiids (ice krill Euphausia crystallorophias and Antarctic krill E. superba), fish (bald notothens Pagothenia borchgrevinki and Antarctic silverfish Pleuragramma antarcticum) and seabirds (Adélie penguins Pygoscelis adeliae, snow petrels Pagodroma nivea and cape petrels Daption capense). This study provides the first evidence of the incorporation of HBI lipids in Antarctic pelagic consumers. Specifically, a di-unsaturated HBI (diene) of sea ice origin was more abundant in ice-associated species than in pelagic species, whereas a tri-unsaturated HBI (triene) of phytoplanktonic origin was more abundant in pelagic species than in ice-associated species. Moreover, the relative abundances of diene and triene in seabird tissues and eggs were higher during a year of good sea ice conditions than in a year of poor ice conditions. In turn, the higher contribution of ice algal derived organic matter to the diet of seabirds was related to earlier breeding and higher breeding success. HBI biomarkers are a promising tool for estimating the contribution of organic matter derived from ice algae in pelagic consumers from Antarctica.
Competition elevates plasma testosterone in a wide variety of vertebrates, including humans. The ‘challenge hypothesis’ proposes that seasonal peaks in testosterone during breeding are caused by social challenges from other males. However, during experimentally induced male–male conflicts, testosterone increases only in a minority of songbird species tested so far. Why is this so? Comparative evidence suggests that species with a short breeding season may not elevate testosterone levels during territory defence. These species may even be limited in their physiological capability to increase testosterone levels, which can be tested by injecting birds with gonadotropin-releasing hormone (GnRH). We studied two populations of black redstarts that differ in breeding altitude, morphology and the length of their breeding season. Unexpectedly, males of neither population increased testosterone in response to a simulated territorial intrusion, but injections with GnRH resulted in a major elevation of testosterone. Thus, black redstarts would have been capable of mounting a testosterone response during the male–male challenge. Our data show, for the first time, that the absence of an androgen response to male–male challenges is not owing to physiological limitations to increase testosterone. Furthermore, in contrast to comparative evidence between species, populations of black redstarts with a long breeding season do not show the expected elevation in testosterone during male–male challenges.
GnRH; challenge hypothesis; number of broods hypothesis; breeding season length; territorial aggression; androgen responsiveness
During the non-breeding period, many birds migrate to milder areas, found closer to the equator than their breeding sites. Opposite movements are very rare. In the Southern Ocean, the abundance of 13C declines markedly with more southern latitude, providing a characteristic 13C isoscape. This can be used as a tracer for the movement of seabirds between breeding and inter-breeding areas, by comparing stable isotope ratios of feathers grown at different times of the year.
We studied seasonal movements of Thin-billed prions (Aves, Procellariiformes), breeding at the Subantarctic Falkland/Malvinas Islands, compared with those of Wilson's storm-petrels breeding in the Antarctic South Shetland Islands. The two species showed opposite migratory movements. While Wilson's storm-petrels moved to warmer waters north of the Drake Passage in winter, Thin-billed prions showed a reversed movement towards more polar waters. Carbon stable isotope ratios in recent and historical feathers indicated that poleward winter movements of Thin-billed prions were less common historically (45% in 1913-1915), and have only recently become dominant (92% in 2003-2005), apparently in response to warming sea temperatures.
This study shows that pelagic seabirds can rapidly change migration strategies within populations, including migration towards more poleward waters in winter.
The effects of a long-acting gonadotropin-releasing hormone (GnRH) agonist, [D-Trp6]-GnRH (GnRH-A) on developmental profiles of plasma luteinizing hormone (LH), follicle stimulation hormone (FSH) and testosterone (T), and pituitary responsiveness to exogenous GnRH were studied in male Dutch Landrace x Large White crossbred pigs from 1 to 30 wk of age. Group 1 control animals (control; n = 12) were injected subcutaneously in the neck with vehicle at 1 and 16 wk of age. Group 2 animals (early treatment; n = 10) were injected with 600 micrograms [D-Trp6]-GnRH at 1 wk and with vehicle at 16 wk. Group 3 animals (late treatment; n = 8) were injected with vehicle and 3 mg GnRH-A at 1 and 16 wk, respectively. Group 4 animals (early plus late treatment; n = 9) were injected at both 1 and 16 wk with GnRH-A. Blood was collected by brachiocephalic puncture at weekly or biweekly intervals, and through brachiocephalic cannulae, to determine longitudinal profiles of LH, FSH and T, and plasma gonadotropin responses to intravenous injection of GnRH (0.1 microgram/kg), respectively. In control animals, LH and FSH declined over the first 5 wk of postnatal life and peaked again at 10-14 wk. Levels of both hormones were basal from 18 to 30 wk. Plasma T was high in the first week, declined progressively over the next few weeks and remained low until 24 wk when a transient increment was noted. The LH and FSH responses to acute GnRH stimulation were similar at 7 and 14 wk and declined significantly at 23 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)
We examined the kinetically distinct characteristics of estradiol's effects upon pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in response to pulses of exogenous gonadotropin-releasing hormone (GnRH) in healthy postmenopausal individuals. The putative self-priming actions of GnRH on LH and FSH release were tested by intravenous injections of equal paired doses of GnRH (10 micrograms) before and after 1, 5, 10, and 30 d of pure estradiol-17 beta delivery via an intravaginal silastic ring. Self-priming actions of GnRH, as defined by heightened gonadotropin release in response to the second pulse of GnRH compared with the first, were completely absent in the hypoestrogenemic state. However, estradiol administration unmasked GnRH self-priming in a time-dependent fashion, with maximal expression after 5 and 10 d of steroid replacement, followed by attenuation by 30 d. Since estradiol's modulation of GnRH action was expressed differentially on LH and FSH release, we suggest that such facilitation of GnRH-stimulated pituitary LH and FSH release may provide an additional mechanism for dissociated secretion of gonadotropic hormones in health or disease.
Mumijo is a widely used traditional medicine, especially in Russia, Altai Mountains, Mongolia, Iran Kasachstan and in Kirgistan. Mumijo preparations have been successfully used for the prevention and treatment of infectious diseases; they display immune-stimulating and antiallergic activity as well. In the present study, we investigate the chemical composition and the biomedical potential of a Mumijo(-related) product collected from the Antarctica. The yellow material originates from the snow petrels, Pagodroma nivea. Extensive purification and chemical analysis revealed that the fossil samples are a mixture of glycerol derivatives. In vitro experiments showed that the Mumijo extract caused in cortical neurons a strong neuroprotective effect against the apoptosis-inducing amyloid peptide fragment β-fragment 25–35 (Aβ25–35). In addition, the fraction rich in glycerol ethers/wax esters displayed a significant growth-promoting activity in permanent neuronal PC12 cells. It is concluded that this new Mumijo preparation has distinct and marked neuroprotective activity, very likely due to the content of glycerol ether derivatives.
Many seasonally breeding avian species exhibit marked changes in hypothalamic content of gonadotropin-releasing vhormone 1 (GNRH1) protein that are reflective of breeding condition. We recently cloned the GNRH1 cDNA in European starlings and demonstrated that changes in GNRH1 mRNA levels occur with a time course similar to what has been observed with GNRH1 protein. However, we did not previously resolve whether these differences were attributable to changes in the number of cells expressing the gene. Herein, we investigated photoperiod-induced changes in the number and distribution of GNRH1 mRNA-expressing cells in the preoptic area of male starlings. GNRH1 mRNA-expressing cell number was significantly greater in breeding birds than in nonbreeding birds. Starlings maintained in short nonstimulatory day length (i.e., prebreeding) showed intermediate cell numbers. Detailed analysis of the rostrocaudal and mediolateral distribution revealed that breeding birds had greater numbers of cells expressing GNRH1 mRNA in the medial intermediate, mediocaudal, and lateral intermediate preoptic area compared with prebreeding and nonbreeding birds. These data demonstrate that photoperiodic changes in reproductive state in starlings are associated with region-specific alterations in the number of cells expressing the GNRH1 gene. It remains to be determined whether these changes reflect quantitative differences in gene expression among an otherwise stable population of cells or a phenotypic switch in which cells gain or lose the ability to make GNRH1 mRNA in response to environmental cues.
Starlings exhibit marked variation in the distribution and number of cells that express gonadotropin-releasing hormone 1 (GNRH1) mRNA in the hypothalamus during differing reproductive states.
gonadotropin-releasing hormone; neuroendocrinology; seasonal reproduction
The Mashona mole-rat, Cryptomys darlingi, exhibits an extreme reproductive division of labour. Reproduction in the colony is restricted to a single breeding pair. The non-reproductive male and female colony members are restrained from sexual activity by being familiar and related to one another and the reproductive animals. Circulating basal concentrations of luteinizing hormone (LH) as well as LH levels measured in response to a single exogenous gonadotropin releasing hormone (GnRH) challenge are not significantly different between the reproductive and non-reproductive groups of either sex. Socially induced infertility in both non-reproductive males and females does not result from a reduced pituitary secretion of LH or decreased sensitivity to hypothalamic GnRH, but rather appears to result from an inhibition of reproductive behaviour in these obligate outbreeders. The African mole-rats exhibit a continuum of socially induced infertility with differing social species inhabiting regions of varying degrees of aridity. In this continuum a transition from a predominantly behavioural repression in a social mesic-adapted species through to complete physiological suppression lacking incest avoidance in an arid-adapted eusocial species occurs in this endemic African family of rodents.
We know very little about physiological constraints on the evolution of life-history traits in general, and, in particular, about physiological and molecular adjustments that accompany the evolution of variation in lifespan. Identifying mechanisms that underlie adaptive variation in lifespan should provide insight into the evolution of trade-offs between lifespan and other life-history traits. Telomeres, the DNA caps at the ends of linear chromosomes, usually shorten as animals age, but whether telomere rate of change is associated with lifespan is unknown. We measured telomere length in erythrocytes from five bird species with markedly different lifespans. Species with shorter lifespans lost more telomeric repeats with age than species with longer lifespans. A similar correlation is seen in mammals. Furthermore, telomeres did not shorten with age in Leach's storm-petrels, an extremely long-lived bird, but actually lengthened. This novel finding suggests that regulation of telomere length is associated not only with cellular replicative lifespan, but also with organismal lifespan, and that very long-lived organisms have escaped entirely any telomeric constraint on cellular replicative lifespan.
The possibility that gonadotrophin releasing hormone (GnRH) can prime the anterior pituitary to a second dose of GnRH resulting in a greatly enhanced secretion of luteinizing hormone was examined in three adult boars. Four experiments were conducted: saline injection followed one hour later by a second saline injection (control); 1 microgram of synthetic GnRH injection followed one hour later by saline injection; saline injection followed one hour later by GnRH injection; GnRH injection followed one hour later by a second GnRH injection. Immunoassayable levels of plasma luteinizing hormone resulting from GnRH plus GnRH treatment were significantly greater than the sum obtained when values from GnRH plus saline and saline plus GnRH were added. Testosterone values in plasma reached maximal concentrations about 60 minutes after peak values of luteinizing hormone were achieved. The results suggest that the first dose of GnRH, in addition to stimulating release of luteinizing hormone can also sensitize the gonadotrophs to a second dose of GnRH causing a significantly greater release of luteinizing hormone.
The timing of the pubertal growth is a critical event in skeletal development. A delay in the onset of puberty has been correlated with increased stress fracture incidence in young women and as a result, suboptimal skeletal development may affect long-term bone strength. Gonadotropin releasing hormone antagonist (GnRH-a) injections were used to delay the onset of puberty in growing female rats. Twenty-three-day-old female rats were injected with a GnRH-antagonist at 2 dosage levels (n =15/group). The low dose group (1.25 mg/kg/dose) received daily injections for 27 days (sacrifice 49 days). The high dose received (5.0mg/kg/dose) only 5 days per week over a 26 day period (sacrifice 48 days). Calcein injections measured bone formation activity on the periosteal and endocortical surfaces. Standard histomorphometric and biomechanical analyses were performed on the femora and ash content was measured on the tibiae of all animals. Serum estradiol and insulin-like growth factor (IGF)-1 levels were assayed. Significant delays in pubertal development occurred in the two GnRH-a groups as evidenced by delayed vaginal openings, decreased uterine and ovarian weights and suppressed estradiol levels compared to control. Femoral lengths were significantly shorter in the experimental groups and serum IGF-1 levels were higher than control. Bone strength and stiffness were significantly lower in the GnRH-a groups. Cortical bone area was decreased and total area was not different between groups. There was a significant decrease in % Ct.Ar/T.Ar. The decreased bone strength may have resulted from a decrease in the amount and distribution of bone, however, stress and Young’s modulus were also decreased. There was a different response between endocortical formation indices and periosteal formation indices to the GnRH-a protocol. Endocortical bone formation rates decreased and there was an increase in periosteal labeled surface. A dose response between bone strength and GnRH-a dosage was found. The data suggest that hypothalamic suppression during pubertal development resulted in decreased bone strength which may result in fracture development.
puberty; hormones; bone histomorphometry; biomechanics; modeling
Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH) agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.
ivf; GnRH; Oocytes; GnRH protocols
The pattern of the gonadotropin-releasing hormone (GnRH) stimulus is critically important in the regulation of pituitary gonadotropin secretion and continuous infusions down-regulate secretion while intermittent pulses maintain luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responsiveness. We examined the effects of pulsatile GnRH administration on pituitary GnRH receptors (GnRH-R) and gonadotropin secretion in the presence of physiological concentrations of testosterone (T) to elucidate the mechanisms and sites of action of GnRH and T on the pituitary gonadotroph. Castrate male rats received one, two, or four testosterone (T) implants (serum T concentrations of 1.1, 2.4, and 5.2 ng/ml, respectively) to suppress endogenous GnRH secretion. Subsequently, intracarotid pulse injections of GnRH (5-250 ng/pulse) or saline in controls were given every 30 min for 48 h, after which gonadotropin responses and pituitary GnRH-R were measured. In control rats, the T implants prevented the rise in GnRH-R that was seen in castrates (empty implant--600 fmol/mg protein) and maintained receptors at the level that was present in intact animals (300 fmol/mg). Pulsatile GnRH administration increased GnRH-R in castrate T-implanted rats, but the response was dependent on the serum T concentration. With one T implant, increasing GnRH doses per pulse stimulated GnRH-R in a linear manner and the maximum receptor concentration (703 +/- 99 fmol/mg) was seen after the 250 ng GnRH dose. In the presence of two T implants, GnRH-R was maximal (705 +/- 45 fmol/mg) after the 25-ng dose and higher doses did not increase receptors above control values. With four T implants, GnRH doses of 5 ng induced a maximum response, 17-50 ng/pulse did not increase GnRH-R, but receptors were again increased by the 250-ng dose (633 +/- 86 fmol/mg). After 48 h of pulsatile GnRH administration there was no correlation between the number of GnRH-R and LH responses to GnRH. In rats with one or two T implants, LH responses were absent after all but the 250-ng doses. In contrast, LH responsiveness was not impaired in the presence of four implants. Thus, low dose GnRH pulses down-regulate LH secretion by an action at a post GnRH-R site, and this effect is regulated by testosterone. The results show that GnRH, given in a pulsatile manner, regulates its own receptor, and physiological increases in serum T produce a 50-fold increase in the sensitivity of GnRH-R stimulation by GnRH.
The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced in the embryonic pituitary in response to delivery of the hypothalamic gonadotropin releasing hormone (GnRH). GnRH has a pivotal role in reestablishing gonadotropin levels at puberty in primates, and for many species with extended reproductive cycles, these are reinitiated in response to central nervous system-induced GnRH release. Thus, a clear role is evident for GnRH in overcoming repression of these genes. Although the mechanisms through which GnRH actively stimulates LH and FSH β-subunit (FSHβ) gene transcription have been described in some detail, there is currently no information on how GnRH overcomes repression in order to terminate reproductively inactive stages. We show here that GnRH overcomes histone deacetylase (HDAC)-mediated repression of the gonadotropin β-subunit genes in immature gonadotropes. The repressive factors associated with each of these genes comprise distinct sets of HDACs and corepressors which allow for differentially regulated derepression of these two genes, produced in the same cell by the same regulatory hormone. We find that GnRH activation of calcium/calmodulin-dependent protein kinase I (CaMKI) plays a crucial role in the derepression of the FSHβ gene involving phosphorylation of several class IIa HDACs associated with both the FSHβ and Nur77 genes, and we propose a model for the mechanisms involved. In contrast, derepression of the LH β-subunit gene is not CaMK dependent. This demonstration of HDAC-mediated repression of these genes could explain the temporal shut-down of reproductive function at certain periods of the life cycle, which can easily be reversed by the actions of the hypothalamic regulatory hormone.
Ecosystems and populations are known to be influenced not only by long-term climatic trends, but also by other short-term climatic modes, such as interannual and decadal-scale variabilities. Because interactions between climatic forcing, biotic and abiotic components of ecosystems are subtle and complex, analysis of long-term series of both biological and physical factors is essential to understanding these interactions. Here, we apply a wavelet analysis simultaneously to long-term datasets on the environment and on the populations and breeding success of three Antarctic seabirds (southern fulmar, snow petrel, emperor penguin) breeding in Terre Adélie, to study the effects of climate fluctuations on Antarctic marine ecosystems. We show that over the past 40 years, populations and demographic parameters of the three species fluctuate with a periodicity of 3–5 years that was also detected in sea-ice extent and the Southern Oscillation Index. Although the major periodicity of these interannual fluctuations is not common to different species and environmental variables, their cyclic characteristics reveal a significant change since 1980. Moreover, sliding-correlation analysis highlighted the relationships between environmental variables and the demography of the three species, with important change of correlation occurring between the end of the 1970s and the beginning of the 1980s. These results suggest that a regime shift has probably occurred during this period, significantly affecting the Antarctic ecosystem, but with contrasted effects on the three species.
climate change; cyclic variability; regime shift; Antarctic marine predators; time-series analysis
Molecular sexing revealed an unexpectedly strong female bias in the sex ratio of pre-breeding European Storm Petrels (Hydrobates pelagicus), attracted to playback of conspecific calls during their northwards migration past SW Europe. This bias was consistent across seven years, ranging from 80.8% to 89.7% female (mean annual sex ratio ± SD = 85.5% female ±4.1%). The sex ratio did not differ significantly from unity (i.e., 50% female) among (i) Storm Petrel chicks at a breeding colony in NW France, (ii) adults found dead on beaches in Southern Portugal, (iii) breeding birds attending nest burrows in the UK, captured by hand, and (iv) adults captured near a breeding colony in the UK using copies of the same sound recordings as used in Southern Europe, indicating that females are not inherently more strongly attracted to playback calls than males. A morphological discriminant function analysis failed to provide a good separation of the sexes, showing the importance of molecular sexing for this species. We found no sex difference in the seasonal or nocturnal timing of migration past Southern Europe, but there was a significant tendency for birds to be caught in sex-specific aggregations. The preponderance of females captured in Southern Europe suggests that the sexes may differ in migration route or in their colony-prospecting behaviour during migration, at sites far away from their natal colonies. Such differences in migration behaviour between males and females are poorly understood but have implications for the vulnerability of seabirds to pollution and environmental change at sea during the non-breeding season.
In seasonally breeding, photoperiodic birds, the development of photorefractoriness is associated with decreased brain expression of gonadotropin-releasing hormone-like immunoreactivity (GnRH-li ir) and increased expression of vasoactive intestinal polypeptide-like immunoreactivity (VIP-li ir). Dissipation of photorefractoriness and reestablishment of photosensitivity are associated with increased GnRH-li ir brain production, but concurrent changes in VIP-li ir expression have not been investigated. To address this question, we compared the expression of VIP-li ir in the infundibulum (INF) of adult male dark-eyed juncos (Junco hyemalis) that were made photorefractory (PR) by prolonged exposure to long days with that of birds that were not photostimulated (PS), but had regained photosensitivity by exposure to short days for 5 (short-term-PS, ST-PS) or 13 (long-term-PS, LT-PS) consecutive months. Photosensitive males had smaller INF VIP-li ir cell bodies than PR males, but the numbers of INF VIP-li ir cells were independent of photoperiodic condition. Changes in infundibular VIP-li ir were correlated with changes in preoptic area (POA) GnRH-li expression. Specifically, photosensitive males had more and larger POA GnRH-li ir cells and more GnRH-li ir fibers in this region than PR males. Further, LT-PS males had more GnRH-li ir POA fibers and larger testes than ST-PS juncos. Thus, induction of photorefractoriness is associated with increased VIP and decreased GnRH brain expression whereas dissipation of photorefractoriness concurs with decreased VIP and increased GnRH brain expression. These results suggest a physiological role for VIP in the control of changes in GnRH expression as a function of the photosensitive condition.
GnRH; VIP; reproduction; prolactin; seasonality; photoperiodism; photosensitivity; photorefractoriness; immunocytochemistry; preoptic area; infundibulum
Gonadotropin-releasing hormone (GnRH) antagonists, which became commercially available from 1999, have been used for the prevention of premature luteinizing hormone (LH) surges in controlled ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. This review focuses on the recent literature on the use of GnRH antagonists and provides guidelines for optimal use in light of increasing evidence showing that GnRH antagonists are safe and effective, allowing flexibility of treatment in a wide range of patient populations. This includes patients undergoing first-line controlled ovarian stimulation, poor responders, and women diagnosed with polycystic ovary syndrome. The GnRH antagonist offers a viable alternative to the long agonists, providing a shorter duration of treatment with fewer injections and with no adverse effects on assisted reproductive technology outcome. This results in a significantly lower amount of gonadotropins required, which is likely to lead to improved patient compliance.
GnRH antagonists; GnRH agonists; IVF; Ovarian stimulation; OHSS
The introduction of a novel male stimulates the hypothalamic-pituitary-gonadal axis of female sheep during seasonal anestrus, leading to the resumption of follicle maturation and ovulation. How this pheromone cue activates pulsatile secretion of gonadotropin releasing hormone (GnRH)/luteinizing hormone (LH) is unknown. We hypothesised that pheromones activate kisspeptin neurons, the product of which is critical for the stimulation of GnRH neurons and fertility. During the non-breeding season, female sheep were exposed to novel males and blood samples collected for analysis of plasma LH profiles. Females without exposure to males served as controls. In addition, one hour before male exposure, a kisspeptin antagonist (P-271) or vehicle was infused into the lateral ventricle and continued for the entire period of male exposure. Introduction of a male led to elevated mean LH levels, due to increased LH pulse amplitude and pulse frequency in females, when compared to females not exposed to a male. Infusion of P-271 abolished this effect of male exposure. Brains were collected after the male effect stimulus and we observed an increase in the percentage of kisspeptin neurons co-expressing Fos, by immunohistochemistry. In addition, the per-cell expression of Kiss1 mRNA was increased in the rostral and mid (but not the caudal) arcuate nucleus (ARC) after male exposure in both aCSF and P-271 treated ewes, but the per-cell content of neurokinin B mRNA was decreased. There was also a generalized increase in Fos positive cells in the rostral and mid ARC as well as the ventromedial hypothalamus of females exposed to males. We conclude that introduction of male sheep to seasonally anestrous female sheep activates kisspeptin neurons and other cells in the hypothalamus, leading to increased GnRH/LH secretion.
Seasonally breeding birds detect environmental signals, such as light, temperature, food availability, and presence of mates to time reproduction. Hypothalamic neurons integrate external and internal signals, and regulate reproduction by releasing neurohormones to the pituitary gland. The pituitary gland synthesizes and releases gonadotropins which in turn act on the gonads to stimulate gametogenesis and sex steroid secretion. Accordingly, how gonadotropin secretion is controlled by the hypothalamus is key to our understanding of the mechanisms of seasonal reproduction. A hypothalamic neuropeptide, gonadotropin-releasing hormone (GnRH), activates reproduction by stimulating gonadotropin synthesis and release. Another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH), inhibits gonadotropin synthesis and release directly by acting on the pituitary gland or indirectly by decreasing the activity of GnRH neurons. Therefore, the next step to understand seasonal reproduction is to investigate how the activities of GnRH and GnIH neurons in the hypothalamus and their receptors in the pituitary gland are regulated by external and internal signals. It is possible that locally-produced triiodothyronine resulting from the action of type 2 iodothyronine deiodinase on thyroxine stimulates the release of gonadotropins, perhaps by action on GnRH neurons. The function of GnRH neurons is also regulated by transcription of the GnRH gene. Melatonin, a nocturnal hormone, stimulates the synthesis and release of GnIH and GnIH may therefore regulate a daily rhythm of gonadotropin secretion. GnIH may also temporally suppress gonadotropin secretion when environmental conditions are unfavorable. Environmental and social milieus fluctuate seasonally in the wild. Accordingly, complex interactions of various neuronal and hormonal systems need to be considered if we are to understand the mechanisms underlying seasonal reproduction.
seasonal reproduction; hypothalamus-pituitary-gonadal axis; gonadotropins; gonadotropin-releasing hormone; gonadotropin-inhibitory hormone; thyroid hormone; melatonin; stress
Secretion from gonadotropin-releasing hormone (GnRH) neurons is necessary for the production of gametes and hormones from the gonads. Subsequently, GnRH release is regulated by steroid feedback. However, the mechanisms by which steroids, specifically estradiol, modulate GnRH secretion are poorly understood. We have previously shown that estradiol administered to the female mouse decreases inward currents in fluorescently-labeled GnRH neurons. The purpose of this study was to examine the contribution of sodium currents in the negative feedback action of estradiol. Electrophysiology was performed on GnRH neurons dissociated from young, middle-aged, or old female mice. All mice were ovariectomized; half were estradiol replaced. The amplitude of the sodium current underlying the action potential was significantly decreased in GnRH neurons from young estradiol-treated animals. In addition, in vivo estradiol significantly decreased the transient sodium current amplitude, but prolonged the sodium current inactivation time constant. Estradiol decreased the persistent sodium current amplitude, and induced a significant negative shift in peak current potential. In contrast to results obtained from cells from young reproductive animals, estradiol did not significantly attenuate the sodium current underlying the action potential in cells isolated from middle-aged or old mice. Sodium channels can modulate cell threshold, latency of firing, and action potential characteristics. The reduction of sodium current amplitude by estradiol suggests a negative feedback on GnRH neurons, which could lead to a downregulation of cell excitability and hormone release. The attenuation of estradiol regulation in peripostreproductive and postreproductive animals could lead to dysregulated hormone release with advancing age.
GnRH; estradiol; transient sodium current; persistent sodium current; aging
Gonadotropin-Releasing Hormone (GnRH) is a small neuropeptide that regulates pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These gonadotropins are essential for the regulation of reproductive function. The GnRH-containing neurons are distributed diffusely throughout the hypothalamus and project to the median eminence where they release GnRH from their axon terminals into the hypophysiotropic portal system (1). In the portal capillaries, GnRH travels to the anterior pituitary gland to stimulate release of gonadotropins into systemic circulation. GnRH release is not continuous but rather occurs in episodic pulses. It is well established that the intermittent manner of GnRH release is essential for reproduction (2, 3).
Coordination of activity of multiple GnRH neurons probably underlies GnRH pulses. Total peptide content in GnRH neurons is approximately 1.0 pg/cell (4), of which 30% likely comprises the releasable pool. Levels of GnRH during a pulse (5, 6), suggest multiple GnRH neurons are probably involved in neurosecretion. Likewise, single unit activity extracted from hypothalamic multi-unit recordings during LH release indicates changes in activity of multiple neurons (7). The electrodes with recorded activity during LH pulses are associated with either GnRH somata or fibers (8). Therefore, at least some of this activity arises from GnRH neurons.
The mechanisms that result in synchronized firing in hypothalamic GnRH neurons are unknown. Elucidating the mechanisms that coordinate firing in GnRH neurons is a complex problem. First, the GnRH neurons are relatively few in number. In rodents, there are 800-2500 GnRH neurons. It is not clear that all GnRH neurons are involved in episodic GnRH release. Moreover, GnRH neurons are diffusely distributed (1). This has complicated our understanding of coordination of firing and has made many technical approaches intractable. We have optimized loose cell-attached recordings in current-clamp mode for the direct detection of action potentials and developed a recording approach that allows for simultaneous recordings from pairs of GnRH neurons.
Although there is increasing evidence that climatic variations during the non-breeding season shape population dynamics of seabirds, most aspects of their winter distribution and ecology remain essentially unknown. We used stable isotope signatures in feathers to infer and compare the moulting (wintering) habitat of subantarctic petrels breeding at two distant localities (South Georgia and Kerguelen). Petrels showed species-specific wintering habitat preferences, with a similar pattern of latitudinal segregation for all but one taxon. At both localities, δ13C values indicated that blue petrels (Halobaena caerulea) moult in Antarctic waters, South Georgian diving petrels (Pelecanoides georgicus) in the vicinity of the archipelagos and/or in the Polar Frontal Zone and Antarctic prions (Pachyptila desolata) in warmer waters. In contrast, common diving petrels (Pelecanoides urinatrix) showed divergent strategies, with low and high intrapopulation variation at South Georgia and Kerguelen, respectively. Birds from Kerguelen dispersed over a much wider range of habitats, from coastal to oceanic waters and from Antarctica to the subtropics, whereas those from South Georgia wintered mainly in waters around the archipelago. This study is the first to show such striking between-population heterogeneity in individual wintering strategies, which could have important implications for likely demographic responses to environmental perturbation.
moulting period; individual specialization; procellariiform seabird; Southern Ocean; Antarctica