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Mst. Parvin MOSTARI Nahoko IEDA Chikaya DEURA Shiori MINABE Shunji YAMADA Yoshihisa UENOYAMA Kei-ichiro MAEDA Hiroko TSUKAMURA 《The Journal of reproduction and development》2013,59(3):266-272
Accumulating evidence suggests that the arcuate nucleus (ARC) kisspeptin/neurokinin B
(NKB)/dynorphin (KNDy) neurons play a role in estrogen negative feedback action on
pulsatile gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release. The
present study aimed to determine if dynorphin (Dyn) is involved in estrogen negative
feedback on pulsatile GnRH/LH release. The effect of the injection of nor-binaltorphimine
(nor-BNI), a kappa-opioid receptor (KOR) antagonist, into the third cerebroventricle (3V)
on LH pulses was determined in ovariectomized (OVX) adult female rats with/without
replacement of negative feedback levels of estradiol (low E2). The mean LH
concentrations and baseline levels of LH secretion in nor-BNI-injected, low
E2-treated rats were significantly higher compared with vehicle-treated
controls. On the other hand, the nor-BNI treatment failed to affect any LH pulse
parameters in OVX rats without low E2 treatment. These results suggest that Dyn
is involved in the estrogen negative feedback regulation of pulsatile GnRH/LH release. The
low E2 treatment had no significant effect on the numbers of ARC
Pdyn (Dyn gene)-,Kiss1- and
Tac2 (NKB gene)-expressing cells. The treatment also did not affect
mRNA levels of Pdyn and Oprk1 (KOR gene) in the
ARC-median eminence region, but significantly increased the ARC kisspeptin
immunoreactivity. These findings suggest that the negative feedback level of estrogen
suppresses kisspeptin release from the ARC KNDy neurons through an unknown mechanism
without affecting the Dyn and KOR expressions in the ARC. Taken together, the present
result suggests that Dyn-KOR signaling is a part of estrogen negative feedback action on
GnRH/LH pulses by reducing the kisspeptin release in female rats. 相似文献
3.
Smith JT 《Domestic animal endocrinology》2012,43(2):75-84
Sheep are seasonal breeders, experiencing an annual period of reproductive quiescence in response to increased photoperiod during the late-winter into spring and renaissance during the late summer. The nonbreeding (anestrous) season is characterized by a reduction in the pulsatile secretion of GnRH from the brain, in part because of an increase in negative feedback activity of estrogen. Neuronal populations in the hypothalamus that produce kisspeptin and gonadotropin-inhibitory hormone (GnIH) appear to be important for the seasonal shift in reproductive activity, and the former are also mandatory for puberty onset. Kisspeptin cells in the arcuate nucleus (ARC) and preoptic area appear to regulate GnRH neurons and transmit sex-steroid feedback signals to these neurons. Moreover, kisspeptin expression in the ARC is markedly up-regulated at the onset of the breeding season, as too are the number of kisspeptin fibers in close apposition to GnRH neurons. The lower levels of kisspeptin seen during the nonbreeding season can be "corrected" by infusion of kisspeptin, which causes ovulation in seasonally acyclic females. The role of GnIH is less clear, but mounting evidence supports a role for this neuropeptide in the inhibitory regulation of both GnRH secretion and gonadotropin release from the pituitary gland. Contrary to kisspeptin, GnIH expression is markedly reduced at the onset of the breeding season. In addition, the number of GnIH fibers in close apposition to GnRH neurons also decreases during this time. Importantly, exogenous GnIH treatment can block both the pulsatile release of LH and the preovulatory LH surge during the breeding season. In summary, it is most likely the integrated function of both these neuropeptide systems that modulate the annual shift in photoperiod to a physiological change in fertility. 相似文献
4.
Yoshihisa UENOYAMA Akira TANAKA Kenji TAKASE Shunji YAMADA Vutha PHENG Naoko INOUE Kei-ichiro MAEDA Hiroko TSUKAMURA 《The Journal of reproduction and development》2015,61(4):351-359
The present study aimed to determine estrogen feedback action sites to mediate prepubertal restraint of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) release in female rats. Wistar-Imamichi strain rats were ovariectomized (OVX) and received a local estradiol-17β (estradiol) or cholesterol microimplant in several brain areas, such as the medial preoptic area (mPOA), paraventricular nucleus, ventromedial nucleus and arcuate nucleus (ARC), at 20 or 35 days of age. Six days after receiving the estradiol microimplant, animals were bled to detect LH pulses at 26 or 41 days of age, representing the pre- or postpubertal period, respectively. Estradiol microimplants in the mPOA or ARC, but not in other brain regions, suppressed LH pulses in prepubertal OVX rats. Apparent LH pulses were found in the postpubertal period in all animals bearing estradiol or cholesterol implants. It is unlikely that pubertal changes in responsiveness to estrogen are due to a change in
estrogen receptor (ER) expression, because the number of ERα-immunoreactive cells and mRNA levels of Esr1, Esr2 and Gpr30 in the mPOA and ARC were comparable between the pre- and postpubertal periods. In addition, kisspeptin or GnRH injection overrode estradiol-dependent prepubertal LH suppression, suggesting that estrogen inhibits the kisspeptin-GnRH cascade during the prepubertal period. Thus, estrogen-responsive neurons located in the mPOA and ARC may play key roles in estrogen-dependent prepubertal restraint of GnRH/LH secretion in female rats. 相似文献
5.
The neuronal control of fertility and sterility has been a subject of research for years. However, nowadays, in spite of considerable literature about GnRH during the last few decades, the precise cellular and molecular mechanisms whereby gonadal steroids and other peripheral signals converge in the brain to achieve the fine regulation of GnRH secretion remains partially unknown. In this scenario, a major breakthrough in our understanding of the neuronal signals governing reproduction took place in 2003 with the discovery of metastin/kisspeptin as a major player in the control of GnRH secretion. This molecule, first described as having a crucial role in triggering the onset of puberty, is involved in all phases of reproductive life and hence has attracted the interest of many reproductive neuroendocrinologists. Administered either centrally or peripherally, kisspeptin strongly induces the secretion of gonadotropin in many species, mainly through stimulation of GnRH secretion. Kisspeptin cells involved in the control of GnRH secretion are located in two regions of the brain: the preoptic area and the arcuate nucleus. Carrying oestradiol receptor alpha, kisspeptin cells of these regions appear to be the main integration centres for the expression of both the positive and negative feedback of steroid on GnRH secretion. More recently, this molecule has been shown to be able to synchronize preovulatory surges in cyclic ewes and cause ovulation in seasonally acyclic ewes. This review summarizes the most relevant aspects of the role of kisspeptin in GnRH/LH release and the potential application of this molecule in new strategies for controlling female fertility. 相似文献
6.
The anteroventral periventricular nucleus (AVPV) of the preoptic area has been implicated in the induction of spontaneous ovulation. In the AVPV, we found a striking sex difference in the distribution of estrogen receptor (ER) positive cells. In females, a significantly larger number of ER mRNA-positive cells were visualized than in males using in situ hybridization in the most medial part of the AVPV next to the ependymal lining of the third ventricle. In males, the labeled cells were dispersed into more lateral region. Immunohistochemistry revealed a similar sexual dimorphism in the ER protein. The dimorphism persisted from Day 7 to Day 60. Orchidectomy of male neonates or estrogen treatment of female pups had reversed the brain phenotype when examined on Day 14. No gross sex difference was detected in the pattern of ER expression in the medial preoptic nucleus and the bed nucleus of the stria terminals. Estrogen receptor immunoreactive cells co-localization in 83% of ER mRNA positive cells in the AVPV of adult females. Infusion of an ER antisense oligonucleotide into the third ventricle resulted in a significantly longer period of successive vaginal estrus and 50% reduction in the number of ER-immunoreactive cells in the AVPV. These findings suggest an important role of ER AVPV in the female-typical estrogen-dependent induction of the luteinizing hormone surge. 相似文献
7.
T Watanabe 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》1992,54(4):723-729
In the present study, attempts were made to evaluate the effects of the estrous cycle and the administration of estradiol (Ovx-E) or progesterone (Ovx-P) after ovariectomy on the threshold of antidromic (AD) and orthodromic (OD) responses of neurons in the medial preoptic area (POA) induced by electrical stimulation of the median eminence-arcuate nucleus (ARC) of the hypothalamus. Single units were evaluated with extracellular recording. The threshold of AD and OD response in POA neurons declined during estrus and proestrus of the estrous cycle and in the Ovx-E group, but increased in the Ovx-P group and during diestrus. The number of neurons with the inhibitory OD response increased during proestrus and in the Ovx-E group, but decreased during diestrus. The neurons with the excitatory OD response increased in the Ovx-P group and during diestrus, and decreased during proestrus. The threshold of the inhibitory and excitatory OD response decreased during proestrus, estrus and in the Ovx-E group, but increased in the Ovx-P group. It is apparent from these studies that estrogen appears to activate the neurons of the POA receiving inhibitory synaptic input via the axonal collateral branches of the ARC neurons, and that progesterone seems to activate the neurons of the POA receiving excitatory synaptic input. 相似文献
8.
A.J. Ziecik W. Sienkiewicz S. Okrasa H. Kalamarz M. Lakomy R.R. Kraeling 《Reproduction in domestic animals》1999,34(6):477-487
Contents The relationship of neuropeptide Y (NPY), galanin (GAL), β-endorphin (β-END) and vasoactive intestinal peptide (VIP) to GnRH neurons were determined during the estradiol-induced LH surge. In experiment 1, 16 ovariectomized (OVX) gilts received 15 μg estradiol benzoate (EB)/kg BW at 0800 h and were slaughtered at either 24 h (n = 5), 48 h (n = 6) or 72 h (n = 5) later and five were injected with corn oil vehicle (0 h controls). Concentrations of neuropeptides were determined in tissue extracts by RIA. In experiment 2, nine OVX gilts were injected with EB as in experiment 1 and killed at either 24, 48 or 72 h (n = 3) later and three were not injected with EB (0 h controls). Frozen sections were processed to localize neuropeptides. In experiment 1, all measured neuropeptides were highest in pituitary stalk median eminence (SME). The GnRH concentration was not different at any time point in medial basal hypothalamus (MBH), preoptic area (POA) or SME. The NPY content in MBH was lower at 24, 48 and 72 h after EB than at 0 h (p < 0.001), and lower in SME at 48 and 72 h than at 24 h (p < 0.05) and 0 h (p < 0.01), respectively. Concentration of GAL in SME was four times higher at 72 h than at 0, 24 or 48 h (p < 0.001). The VIP concentration increased in POA (p < 0.05) and MBH (p < 0.001) at 24 h and 72 h (p < 0.05). Concentration of VIP in SME was lower at 24 and 48 h than at 0 h (p < 0.05) and increased to more than twice (p < 0.05) by 72 h. Concentrations of β-END were not different at any time point in POA and MBH but the highest content of β-END in SME occurred at 24 h (p < 0.001). In experiment 2 a moderate number of GnRH-immunoreactive (IR) fibres were found in the periventricular area of the POA and in organum vasculosum of the laminae terminalis (OVLT). The GnRH-IR fibres formed networks in the external and internal layer of the median eminence (ME). At 24 h, GnRH-IR neurons and fibres in the POA and ME were more numerous and noticeable differences were found in the arcuate nucleus (ARC) and ventromedial nucleus (NVM). At 48 and 72 h, numbers of IR neurons and fibres were higher in the ARC and NVM, but no changes occurred in the POA and ME. The ARC contained a moderate number of NPY-IR fibres, but less numerous small cell bodies. Only a few NPY-IR perikarya and fibres were in the NVM and fibre density was similar at all times after EB injection. VIP-IR fibres were scarcely distributed mostly in the posterior POA and the internal layer of ME. The number of VIP-IR fibres was similar at all time points and regions. A moderate number of varicose β-END fibres supplied the POA, and they were especially dense near the OVLT, but the cell bodies were moderate in number and did not show strong immunoreactivity. In ME, ARC and NVM, the number of β-END immunoreactive structures was greater at 24 and 48 h than at 0 h. The number of β-END-IR nerve fibres in POA was higher at 72 h than at 0 h. Levels of all neuropeptides studied were similar in the POA and MBH and content of NPY, GAL and β-END was very high in the SME of the pig forebrain. The dynamic changes of NPY, GAL, VIP and β-END content in pig hypothalamus during the oestrogen-induced negative and positive feedback phases of LH secretion indicate their potential role in modulating GnRH release from the median eminence. 相似文献
9.
Increasing plasma estrogen (E) levels during the follicular phase of the estrous cycle trigger the pre-ovulatory surge of gonadotropin-releasing hormone (GnRH)/LH. Noradrenaline (NA)-producing cells of the brain stem are involved in regulating GnRH cells and project to the preoptic area (POA) and bed nucleus of stria terminalis (BnST). Input to GnRH cells may be direct or indirect, via relay neurons in the POA/BnST. To investigate this, we ascertained whether an 1-adrenergic antagonist would block/delay the LH surge in ovariectomised (OVX), E-treated ewes. E benzoate (EB) (50 μg) was injected (i.m.) and Doxazosin (100 nmol/h) or vehicle was infused into the third ventricle 2–26 h after EB injection. Doxazosin reduced the magnitude of the LH surge, but did not affect timing. To determine if NA is released in the POA/BnST of cyclic ewes, we immunostained dopamine-β-hydroxylase (DBH) in terminal fields. Reduced numbers of varicosities staining for DBH indicates release of NA. The number of varicosities immunostained for DBH was reduced in the dorsal and lateral BnST during the follicular phase and during the preovulatory LH surge compared to the luteal phase. These data suggest that noradrenergic mechanisms are involved in generation of the GnRH/LH surge via projections to the BnST and relay to GnRH cells. Since Doxasozin reduced the magnitude of the LH surge in the E-treated OVX ewe, and release of NA in cyclic ewes occurred during the follicular phase of the estrous cycle, we speculate that NA is a permissive factor in surge generation. Thus, increased noradrenergic activity is not a trigger mechanism for initiation of the surge. 相似文献
10.
Tomomi TANAKA Satoshi OHKURA Yoshihiro WAKABAYASHI Takenobu KUROIWA Kiyosuke NAGAI Natsumi ENDO Akira TANAKA Hisanori MATSUI Masami KUSAKA Hiroaki OKAMURA 《The Journal of reproduction and development》2013,59(6):563-568
The aim of the present study was to determine if the estradiol-induced luteinizing
hormone (LH) surge is influenced by the constant exposure to TAK-683, an
investigational metastin/kisspeptin analog, that had been established to depress the
pulsatile gonadotropin-releasing hormone (GnRH) and LH secretion in goats.
Ovariectomized goats subcutaneously received TAK-683 (TAK-683 group, n=6) or vehicle
(control group, n=6) constantly via subcutaneous implantation of an osmotic pump.
Five days after the start of the treatment, estradiol was infused intravenously in
both groups to evaluate the effects on the LH surge. Blood samples were collected at
6-min intervals for 4 h prior to the initiation of either the TAK-683 treatment or
the estradiol infusion, to determine the profiles of pulsatile LH secretion. They
were also collected at 2-h intervals from –4 h to 32 h after the start of estradiol
infusion for analysis of LH surges. The frequency and mean concentrations of LH
pulses in the TAK-683 group were remarkably suppressed 5 days after the start of
TAK-683 treatment compared with those of the control group (P<0.05). On the other
hand, a clear LH surge was observed in all animals of both groups. There were no
significant differences in the LH concentrations for surge peak and the peak time of
the LH surge between the TAK-683 and control groups. These findings suggest that the
effects of continuous exposure to kisspeptin or its analog on the mechanism(s) that
regulates the pulsatile and surge mode secretion of GnRH/LH are different in
goats. 相似文献
11.
Murata K Wakabayashi Y Sakamoto K Tanaka T Takeuchi Y Mori Y Okamura H 《The Journal of reproduction and development》2011,57(2):197-202
Exposure of females to the male pheromone induces pulsatile release of gonadotropin-releasing hormone (GnRH) in goats. Recently, kisspeptin neurons in the arcuate nucleus (ARC) have been suggested to represent the proximate source of the GnRH pulse generator. In this study, we examined the effects of the pheromone on multiple-unit activity (MUA) in female goats fitted with recording electrodes aimed at the ARC kisspeptin neurons. In all eight goats, periodic bursts in MUA (MUA volleys), which were considered to be electrophysiological manifestations of the GnRH pulse generator, were observed. The mean intervolley interval (T) during the control period was calculated in each goat that was then exposed to the male pheromone for 1 sec at timings of 1/4 T, 1/2 T or 3/4 T after one regularly occurring MUA volley. An instantaneous rise in MUA was observed immediately after the exposure regardless of timing. Exposure at a timing of 3/4 T resulted in an MUA volley within 60 sec following the instantaneous rise in all goats. In contrast, an MUA volley was induced in only 2 goats by exposure at 1/2 T, while exposure at 1/4 T failed to induce an MUA volley in any goats. These results suggest that transmission of the pheromone signal to the ARC, represented by an instantaneous rise, activates the GnRH pulse generator. Moreover, the timing-dependent pheromone action in inducing an MUA volley indicates that the GnRH pulse generator has a refractory period for the pheromone signal after the burst. 相似文献
12.
Yoshihiro WAKABAYASHI Hiroaki OKAMURA Takashi YAMAMURA 《The Journal of reproduction and development》2021,67(6):352
Kisspeptin neurons in the arcuate nucleus (ARC), which co-express neurokinin B (NKB) and dynorphin A, are termed KNDy neurons. These neurons are candidates for the intrinsic gonadotropin-releasing hormone (GnRH) pulse generator. The central and peripheral administration of NKB or its receptor (NK3R) agonist evokes GnRH pulse generator activity and the subsequent pulsatile GnRH/luteinizing hormone (LH) secretion. However, the mechanism responsible for neural activation of the GnRH pulse generator in goats is unclear. We conducted electrophysiological and histochemical experiments to test the hypothesis that KNDy neurons receive NKB and that the signal is transmitted bilaterally to a population of KNDy neurons. Bilateral electrodes aimed at a cluster of KNDy neurons were inserted into the ovariectomized goat ARC. We observed the GnRH pulse generator activity, represented by characteristic increases in multiple-unit activity (MUA volleys). The unilateral administration of NKB or vehicle in the close vicinity of KNDy neurons under simultaneous MUA recording from both sides revealed that only NKB evoked MUA volley(s) immediately after administration. The timing of the MUA volley(s) evoked on the ipsilateral side was synchronized to that on the contralateral side. The double-labeled ISH for KISS1 and TACR3, which encode kisspeptin and NK3R, respectively, revealed that most KNDy neurons co-expressed TACR3. Therefore, NKB could directly stimulate KNDy neurons, following which the stimulatory signal is immediately transmitted to the entire population of KNDy neurons via connection with their fibers. This mechanism helps synchronize burst activity among KNDy neurons, thereby generating neural signals that govern pulsatile GnRH secretion. 相似文献
13.
Nahoko IEDA Yoshihisa UENOYAMA Yoko TAJIMA Tomoko NAKATA Masatoshi KANO Yousuke NANIWA Youki WATANABE Shiori MINABE Junko TOMIKAWA Naoko INOUE Fuko MATSUDA Satoshi OHKURA Kei-ichiro MAEDA Hiroko TSUKAMURA 《The Journal of reproduction and development》2014,60(4):312-316
Puberty is associated with an increase in gonadotropin secretion as a result of an increase in gonadotropin-releasing hormone
(GnRH) secretion. Kisspeptin is considered to play a key role in puberty onset in many mammalian species, including rodents,
ruminants and primates. The present study aimed to determine if changes in hypothalamic expression of the KISS1
gene, encoding kisspeptin, are associated with the onset of puberty in pigs. The animals (n=4 in each group) were perfused with 4%
paraformaldehyde at 0, 1, 2, 3 and 4 months old, as prepubertal stages, and at 5 months old, as the peripubertal stage, following
each blood sampling. KISS1 gene expressions in coronal sections of brains were visualized by in
situ hybridization. Plasma luteinizing hormone (LH) was measured by radioimmunoassay. KISS1 mRNA
signals were observed in the arcuate nucleus (ARC) at all ages examined without any significant difference in the number of
KISS1-expressing cells, indicating that the KISS1 gene is constantly expressed in the ARC
throughout pubertal development in pigs. The plasma LH concentration was the highest in 0-month-old piglets and significantly
decreased in the 1- and 2 month-old groups (P<0.05), suggesting a developing negative feedback mechanism affecting gonadotropin
release during the prepubertal period. Considering the potent stimulating effect of kisspeptin on gonadotropin release in
prepubertal pigs, kisspeptin secretion rather than kisspeptin synthesis may be responsible for the onset of puberty in pigs. 相似文献
14.
Yoshihiro WAKABAYASHI Takashi YAMAMURA Kohei SAKAMOTO Yuji MORI Hiroaki OKAMURA 《The Journal of reproduction and development》2013,59(1):40-48
Neurons in the arcuate nucleus (ARC) that concomitantly express kisspeptin, neurokinin B
(NKB) and dynorphin A are termed KNDy neurons and are likely candidates for the intrinsic
gonadotropin-releasing hormone (GnRH) pulse generator. Our hypothesis is that KNDy neurons
are functionally and anatomically interconnected to generate discrete neural signals that
govern pulsatile GnRH secretion. Our goal was to address this hypothesis using
electrophysiological and anatomical experiments in goats. Bilateral electrodes targeting
KNDy neurons were implanted into ovariectomized goats, and GnRH pulse generator activity,
represented by characteristic increases in multiple-unit activity (MUA volleys), was
measured. Spontaneous and pheromone- or senktide (an NKB receptor agonist)-induced MUA
volleys were simultaneously recorded from both sides of the ARC. An anterograde tracer,
biotinylated dextran amine (BDA), was also injected unilaterally into the ARC of castrated
male goats, and the distribution of fibers containing both BDA and NKB was examined using
dual-labeling histochemistry. The results showed that MUA volleys, regardless of origin
(spontaneous or experimentally induced), occur simultaneously between the right and left
sides of the ARC. Tract tracing indicated that axons projecting from NKB neurons in the
ARC were directly apposed to other NKB neuronal cells located bilaterally in the ARC.
These results demonstrate that GnRH pulse generator activity occurs synchronously between
both sides of the ARC in goats and that KNDy neurons are bilaterally interconnected in the
ARC via NKB-containing fibers. Taken together, the results suggest that KNDy neurons form
a neuronal circuit to synchronize burst activity among KNDy neurons and thereby generate
discrete neural signals that govern pulsatile GnRH secretion. 相似文献
15.
Arisa SUGIMOTO Hitomi TSUCHIDA Mayuko NAGAE Naoko INOUE Yoshihisa UENOYAMA Hiroko TSUKAMURA 《The Journal of reproduction and development》2022,68(3):190
Reproductive function is suppressed during lactation owing to the suckling-induced suppression of the kisspeptin gene (Kiss1) expression in the arcuate nucleus (ARC) and subsequent suppression of luteinizing hormone (LH) release. Our previous study revealed that somatostatin (SST) neurons mediate suckling-induced suppression of LH release via SST receptor 2 (SSTR2) in ovariectomized lactating rats during early lactation. This study examined whether central SST-SSTR2 signaling mediates the inhibition of ARC Kiss1 expression and LH release in lactating rats during late lactation and whether the inhibition of glutamatergic neurons, stimulators of LH release, is involved in the suppression of LH release mediated by central SST-SSTR2 signaling in lactating rats. A central injection of the SSTR2 antagonist CYN154806 (CYN) significantly increased ARC Kiss1 expression in lactating rats on day 16 of lactation. Dual in situ hybridization revealed that few ARC Kiss1-positive cells co-expressed Sstr2, and some of the ARC Slc17a6 (a glutamatergic neuronal marker)-positive cells co-expressed Sstr2. Furthermore, almost all ARC Kiss1-positive cells co-expressed Grin1, a subunit of N-methyl-D-aspartate (NMDA) receptors. The numbers of Slc17a6/Sstr2 double-labeled and Slc17a6 single-labeled cells were significantly lower in lactating dams than in non-lactating rats whose pups had been removed after parturition. A central injection of an NMDA antagonist reversed the CYN-induced increase in LH release in lactating rats. Overall, these results suggest that central SST-SSTR2 signaling, at least partly, mediates the suppression of ARC Kiss1 expression and LH release by inhibiting ARC glutamatergic interneurons in lactating rats. 相似文献
16.
M.-E. Sébert D. LometS. Ben Saïd P. MongetC. Briant R.J. ScaramuzziA. Caraty 《Domestic animal endocrinology》2010
We have previously demonstrated that a constant intravenous infusion of kisspeptin (Kp) for 48 h in anestrous ewes induces a preovulatory luteinizing hormone (LH) surge followed by ovulation in approximately 75% of animals. The mechanisms underlying this effect are unknown. In this study, we investigated whether Kp-induced preovulatory LH surges in anestrous ewes were the result of the general activation of the whole gonadotropic axis or of the direct activation of central GnRH neurons required for the GnRH/LH surge. In the first experiment, a constant iv infusion of ovine kisspeptin 10 (Kp; 15.2 nmol/h) was given to 11 seasonally acyclic ewes over 43 h. Blood samples were taken every 10 min for 15 h, starting 5 h before the infusion, and then hourly until the end of the infusion. We found that the infusion of Kp induced a well-synchronized LH surge (around 22 h after the start of the Kp infusion) in 82% of the animals. In all ewes with an LH surge, there was an immediate but transient increase in the plasma concentrations of LH, follicle-stimulating hormone (FSH), and growth hormone (GH) at the start of the Kp infusion. Mean (± SEM) concentrations for the 5-h periods preceding and following the start of the Kp infusion were, respectively, 0.33 ± 0.09 vs 2.83 ± 0.49 ng/mL (P = 0.004) for LH, 0.43 ± 0.05 vs 0.55 ± 0.03 ng/mL (P = 0.015) for FSH, and 9.34 ± 1.01 vs 11.51 ± 0.92 ng/mL (P = 0.004) for GH. In the first experiment, surges of LH were observed only in ewes that also had a sustained rise in plasma concentrations of estradiol (E2) in response to Kp. Therefore, a second experiment was undertaken to determine the minimum duration of Kp infusion necessary to induce such a pronounced and prolonged increase in plasma E2 concentration. Kisspeptin (15.2 nmol/h) was infused for 6, 12, or 24 h in seasonally acyclic ewes (N = 8), and blood samples were collected hourly for 28 h (beginning 5 h before the start of infusion), then every 2 h for the following 22 h. Kisspeptin infused for 24 h induced LH surges in 75% of animals, and this percentage decreased with the duration of the infusion (12 h = 50%; 6 h = 12.5%). The plasma concentration of E2 was greater in ewes with an LH surge compared to those without LH surges; mean (± SEM) concentrations for the 5-h period following the Kp infusion were, respectively, 2.23 ± 0.16 vs 1.27 ± 0.13 pg/mL (P < 0.001). Collectively, our results strongly suggest that the systemic delivery of Kp induced LH surges by activating E2-positive feedback on gonadotropin secretion in acyclic ewes. 相似文献
17.
Jaroenporn S Horii Y Akieda-Asai S Wang K Nagaoka K Ohta R Shirota M Watanabe G Taya K 《The Journal of reproduction and development》2011,57(6):690-699
Hatano high- and low-avoidance rats (HAA and LAA strains, respectively) were selected and bred according to the avoidance rate in a shuttle-box task. Although they have clear strain differences in ovarian function, their endocrine mechanisms still remain to be clarified. Differences in female reproductive endocrinology between the strains were investigated by means of measuring the plasma concentration of reproductive hormones during the estrous cycle. LAA rats showed approximately threefold lower basal and surge levels of LH, a more than fourfold lower level of FSH surges and higher levels of inhibin A and inhibin B during the estrous cycle compared with the levels seen in HAA rats. The concentration of estradiol-17β in the proestrous stage was significantly lower in LAA rats than in HAA rats. Additionally, LH and FSH secretions from primary cultured anterior pituitary cells with or without in vitro GnRH stimulation were lower in the cells derived from LAA rats and, in terms of FSH secretion, were unresponsive to GnRH in contrast to cells derived from HAA rats. Although an increased number of preantral follicles in diestrus were observed in LAA rats, number of hCG-induced ovulation was lower in LAA rats. LAA rats may have much more follicle growth during the early stage of folliculogenesis, but most follicles might not grow into mature follicles. These results strongly suggest that the strain difference in ovarian function of these two Hatano rats is due to the difference in the regulation of hypothalamo-hypophyseal system for gonadotropins secretion. 相似文献
18.
In vitro responsiveness of the horse anterior pituitary (AP) gonadotropes to single and multiple GnRH challenges was examined. The pituitaries were collected from reproductively sound mares in estrus (n = 5) and diestrus (n = 5). Uniform 0.5 mm AP slices were subdivided using a 3 mm biopsy punch and then bisected for use in the perifusion chamber. Four bisected sections per chamber were perifused at 0.5 ml/min at 37 C for 560 min in Medium 199 saturated with 95% 0(2)/5% CO2. Ten minute fractions were collected after an initial 2 hr equilibration period. Four different treatment regimes of GnRH (10(-10) M) were evaluated: (A) three consecutive 10 min GnRH pulses separated by 80 and 100 min, respectively; (B) a single 120 min GnRH infusion; (C) a 10 min GnRH pulse followed 80 min later by a 120 min GnRH infusion and (D) two 10 min GnRH pulses separated by 60 min followed 80 min later by a 120 min GnRH infusion. Estimated total pituitary LH content was higher in estrous than diestrus mares (p less than 0.05). The total amount of LH released in response to GnRH tended to be greater in estrus than diestrus (p less than 0.1), whereas the percentage of LH released in estrus and diestrus was similar. An increase in the area under the LH response curve was noted with each successive 10 min pulse of GnRH during both estrus and diestrus (p less than 0.05), demonstrating a self-priming effect of GnRH. In addition, a significant increase in the peak LH amplitude (p less than 0.05) and the slope to peak amplitude (p less than 0.05) were observed for the 120 min GnRH pulse in regime C and D indicating that prior exposure to short-term pulses of GnRH increased the acute LH secretory response. These results suggest that in the cycling mare (1) the responsiveness of the pituitary (amount of LH released as percent of total LH) is similar in both estrus and diestrus, however, the magnitude of the LH response (total microgram amount of LH released) differs with the stage of the estrous cycle, being highest in estrus, and appears to be related, in part, to pituitary LH content and (2) GnRH self-priming occurs independently of the stage of the estrous cycle. Furthermore, we have demonstrated that the pulsatile mode of GnRH can act directly on the anterior pituitary to dictate the pulsatile release pattern of LH in the cycling mare. 相似文献
19.
C Fergani JE Routly DN Jones LC Pickavance RF Smith H Dobson 《Reproduction in domestic animals》2014,49(3):433-440
Normal reproductive function is dependent upon availability of glucose and insulin‐induced hypoglycaemia is a metabolic stressor known to disrupt the ovine oestrous cycle. We have recently shown that IIH has the ability to delay the LH surge of intact ewes. In the present study, we examined brain tissue to determine: (i) which hypothalamic regions are activated with respect to IIH and (ii) the effect of IIH on kisspeptin cell activation and CRFR type 2 immunoreactivity, all of which may be involved in disruptive mechanisms. Follicular phases were synchronized with progesterone vaginal pessaries and at 28 h after progesterone withdrawal (PW), animals received saline (n = 6) or insulin (4 IU/kg; n = 5) and were subsequently killed at 31 h after PW (i.e., 3 h after insulin administration). Peripheral hormone concentrations were evaluated, and hypothalamic sections were immunostained for either kisspeptin and c‐Fos (a marker of neuronal activation) or CRFR type 2. Within 3 h of treatment, cortisol concentrations had increased whereas plasma oestradiol concentrations decreased in peripheral plasma (p < 0.05 for both). In the arcuate nucleus (ARC), insulin‐treated ewes had an increased expression of c‐Fos. Furthermore, the percentage of kisspeptin cells co‐expressing c‐Fos increased in the ARC (from 11 to 51%; p < 0.05), but there was no change in the medial pre‐optic area (mPOA; 14 vs 19%). CRFR type 2 expression in the lower part of the ARC and the median eminence was not altered by insulin treatment. Thus, disruption of the LH surge after IIH in the follicular phase is not associated with decreased kisspeptin cell activation or an increase in CRFR type 2 in the ARC but may involve other cell types located in the ARC nucleus which are activated in response to IIH. 相似文献
20.
Yousuke NANIWA Keisuke NAKATSUKASA Shohei SETSUDA Shinya OISHI Nobutaka FUJII Fuko MATSUDA Yoshihisa UENOYAMA Hiroko TSUKAMURA Kei-ichiro MAEDA Satoshi OHKURA 《The Journal of reproduction and development》2013,59(6):588-594
Kisspeptin is a key molecule that stimulates gonadotropin secretion via release of
gonadotropin-releasing hormone (GnRH). In the present study, our aim was to
investigate whether kisspeptin has stimulatory effects on follicular development via
GnRH/gonadotropin secretion in cows. Japanese Black beef cows were intravenously
injected with full-length bovine kisspeptin [Kp-53 (0.2 or 2 nmol/kg)] or vehicle 5
days after they exhibited standing estrus (Day 0). In cows injected with Kp-53 at 2
nmol/kg, the follicular sizes of the first dominant follicles increased on Day 6 and
thereafter. Ovulation of the first dominant follicle occurred in 1 out of 4 cows
treated with Kp-53 at 2 nmol/kg. Injection of Kp-53 at 2 nmol/kg increased the
concentration of plasma luteinizing hormone (LH) but not follicle-stimulating
hormone, over a 4-h period following injection in all cows. The present study
suggests that administration of full-length kisspeptin causes LH secretion, which is
sustained for a few hours, and it is capable of stimulating follicular development
and/or ovulation. 相似文献