Kiss1 Gene Expression Research Articles

Kisspeptin-1 regulates forebrain dopaminergic neurons in the zebrafish

The habenula is a phylogenetically conserved epithalamic structure, which conveys negative information via inhibition of mesolimbic dopamine neurons. We have previously shown the expression of kisspeptin (Kiss1) in the habenula and its role in the modulation of fear responses in the zebrafish. In this study, to investigate whether habenular Kiss1 regulates fear responses via dopamine neurons in the zebrafish, Kiss1 peptides were intracranially administered close to the habenula, and the expression of dopamine-related genes (th1, th2 and dat) were examined in the brain using real-time PCR and dopamine levels using LC–MS/MS. th1 mRNA levels and dopamine levels were significantly increased in the telencephalon 24-h and 30-min after Kiss1 administration, respectively. In fish administered with Kiss1, expression of neural activity marker gene, npas4a and kiss1 gene were significantly decreased in the ventral habenula. Application of neural tracer into the median raphe, site of habenular Kiss1 neural terminal projections showed tracer-labelled projections in the medial forebrain bundle towards the telencephalon where dopamine neurons reside. These results suggest that Kiss1 negatively regulates its own neuronal activity in the ventral habenula via autocrine action. This, in turn affects neurons of the median raphe via interneurons, which project to the telencephalic dopaminergic neurons.

The Role of Zingiber officinale (Ginger) Extract in the Kiss1 Gene Expression in the Ovary and Blood of Wistar Rats

The Role of Zingiber officinale (Ginger) Extract in the Kiss1 Gene Expression in the Ovary and Blood of Wistar Rats

Influences of Serotonin Hydrochloride on Adiponectin, Ghrelin and KiSS1 Genes Expression.

Background: Serotonin and kisspeptin stimulates gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release while ghrelin and adiponectin inhibit them. In the present experimental study, the effects of central injection of serotonin were investigated on LH concentration, KiSS1, adiponectin, and ghrelin genes expression. Materials and Methods: Fifteen Wistar male rats in three groups received saline or serotonin hydrochloride via the third cerebral ventricle. Blood samples were collected via the tail vein. Serum LH concentration and relative gene expression were evaluated by radioimmunoassay and real-time polymerase chain reaction method, respectively. Results: Serotonin significantly increased the mean serum LH concentration and KiSS1 gene expression levels compared to the saline group. Serotonin significantly decreased the mean ghrelin and adiponectin genes expression levels compared to the saline group. Conclusion: The serotonergic pathway may have stimulatory effects on hypothalamic kisspeptin synthesis, partly via inhibiting hypothalamic ghrelin and adiponectin neural activity.

Influences of Serotonin Hydrochloride on Adiponectin, Ghrelin and KiSS1 Genes Expression

Background: Serotonin and kisspeptin stimulates gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release while ghrelin and adiponectin inhibit them. In the present experimental study, the effects of central injection of serotonin were investigated on LH concentration, KiSS1, adiponectin, and ghrelin genes expression. Materials and Methods: Fifteen Wistar male rats in three groups received saline or serotonin hydrochloride via the third cerebral ventricle. Blood samples were collected via the tail vein. Serum LH concentration and relative gene expression were evaluated by radioimmunoassay and real-time polymerase chain reaction method, respectively. Results: Serotonin significantly increased the mean serum LH concentration and KiSS1 gene expression levels compared to the saline group. Serotonin significantly decreased the mean ghrelin and adiponectin genes expression levels compared to the saline group. Conclusion: The serotonergic pathway may have stimulatory effects on hypothalamic kisspeptin synthesis, partly via inhibiting hypothalamic ghrelin and adiponectin neural activity.[GMJ.2020;9:e1767]

Bisphenol A and Puberty Onset in Female Mice: Developmental Effects of Low-Dose Exposure.

Bisphenol A and Puberty Onset in Female Mice: Developmental Effects of Low-Dose Exposure.

Roles of intracerebral activin, inhibin, and follistatin in the regulation of Kiss-1 gene expression: Studies using primary cultures of fetal rat neuronal cells

Hypothalamic kisspeptin, encoded by the Kiss-1 gene, governs the hypothalamic-pituitary-gonadal axis by directly regulating the release of gonadotropin-releasing hormone. In this study, we examined the roles of activin, inhibin, and follistatin in the regulation of Kiss-1 gene expression using primary cultures of fetal rat neuronal cells, which express the Kiss-1 gene and kisspeptin. Stimulation with activin significantly increased Kiss-1 gene expression in these cultures by 2.02 ± 0.39-fold. In contrast, a significant decrease in Kiss-1 gene expression was observed with inhibin A and follistatin treatment. Inhibin B did not modulate Kiss-1 gene expression. Activin, inhibin, and follistatin were also expressed in fetal rat brain cultures and their expression was controlled by estradiol (E2). The inhibin α, βA, and βB subunits were upregulated by E2. Similarly, follistatin gene expression was significantly increased by E2 in these cells. Our results suggest the possibility that activin, inhibin, and follistatin expressed in the brain participate in the E2-induced feedback control of the hypothalamic-pituitary-gonadal axis.

SUN-244 Role of Activin, Follistatin, and Inhibin in the Regulation of KISS-1 Gene Expression in Hypothalamic Cell Models

Kisspeptin (encoded by the Kiss-1 gene) in the arcuate nucleus (ARC) of the hypothalamus governs the hypothalamic-pituitary-gonadal (HPG) axis by regulating pulsatile release of gonadotropin-releasing hormone (GnRH). Meanwhile, kisspeptin in the anteroventral periventricular nucleus (AVPV) region has been implicated in estradiol (E2)-induced GnRH surges. Kiss-1-expressing cell model mHypoA-55 exhibits characteristics of Kiss-1 neurons in the ARC region. On the other hand, Kiss-1 expressing mHypoA-50 cells originate from the AVPV region. In the mHypoA-55 ARC cells, activin significantly increased Kiss-1 gene expression. Follistatin alone reduced Kiss-1 expression within these cells. Interestingly, activin-induced Kiss-1 gene expression was completely abolished by follistatin. Inhibin A, but not inhibin B reduced Kiss-1 expression. Activin-increased Kiss-1 expression was also abolished by inhibin A. Pretreatment of the cells with follistatin or inhibin A significantly inhibited kisspeptin- or GnRH-induced Kiss-1 gene expression in mHypoA-55 cells. In contrast, in the mHypoA-50 AVPV cell model, activin, follistatin, and inhibin A did not modulate Kiss-1 gene expression. The subunits that compose activin and inhibin, as well as follistatin were expressed in both mHypoA-55 and mHypoA-50 cells. Expression of inhibin βA and βB subunits and follistatin was much higher in mHypoA-55 ARC cells. Furthermore, we found that expression of the inhibin αsubunit and follistatin genes was modulated in the presence of E2 in mHypoA-55 ARC cells. The results of this study suggest that activin, follistatin, and inhibin A within the ARC region participate in the regulation of the HPG axis under the influence of E2.

SUN-250 Effects of Anti-Mullerian Hormone on the Expression of Gonadotropin Subunits in Pituitary Gonadotroph Cell Models

Aim: We examined the effect of anti-Müllerian hormone (AMH) on the expression of gonadotropin subunits in pituitary gonadotrophs.Methods: The mouse pituitary gonadotroph cell line LβT2 was stimulated with AMH and the expression levels of gonadotropin subunits were determined by real-time PCR. We also examined the involvement of the Kiss-1 gene (encoding kisspeptin) and the kisspeptin receptor (Kiss-1R) in LβT2 cells. Results: A significant increase was observed in the expression level of the FSHβ subunit with AMH but not in the expression levels of gonadotropin α and LHβ subunits. A significant decrease was observed in the expression of Kiss-1 and Kiss-1R genes in LβT2 cells with AMH stimulation. Kiss-1 gene knockdown by siRNA did not alter the basal expression of gonadotropin subunits. When LβT2 cells overexpressing Kiss-1R were stimulated with kisspeptin, there was a significant increase in the gene expression levels of the gonadotropin subunits α, LHβ, and FSHβ. This inductive effect of kisspeptin was almost completely inhibited by AMH pretreatment. The GnRH-induced increase in gonadotropin subunit genes was unchanged in the presence of AMH. Conclusions: AMH can increase FSHβ subunit gene expression in pituitary gonadotroph cells. However, AMH decreases Kiss-1 and Kiss-1R gene expression within the gonadotrophs. Because AMH pretreatment abolishes kisspeptin-induced expression of gonadotropin subunit genes, AMH may control kisspeptin-regulated gonadotropin expression by inhibiting the expression and function of Kiss-1R within gonadotrophs.

SUN-LB57 Assessing the Requirement of Arcuate Nucleus Kisspeptin Neurons in Puberty Onset and Adult LH Secretion

Puberty is a critical developmental period marking the transition to adulthood and attainment of reproductive capability. A hallmark of puberty is increased pulsatile secretion of pituitary luteinizing hormone (LH) which is itself driven by increased gonadotropin-releasing hormone (GnRH) from the forebrain. The mechanisms governing GnRH neuron activation at puberty still remain unclear, but likely include enhanced stimulation from upstream reproductive neural circuits, including kisspeptin neurons. Kisspeptin is a potent stimulator of GnRH and is required for proper puberty onset. However, the specific brain site(s) from where kisspeptin signaling arises to trigger puberty remain unclarified. Kisspeptin is expressed in two primary nuclei in the hypothalamus, the arcuate nucleus (ARC) and anteroventral periventricular (AVPV) region. Studies suggest that, in adulthood, ARC Kiss1 neurons are involved in driving pulsatile secretion of GnRH (and hence, LH) in both sexes whereas AVPV Kiss1 neurons participate in the preovulatory GnRH/LH surge in females. However, the specific role of either kisspeptin neuron population in puberty onset still remains unknown. We previously showed that both kisspeptin populations show increased Kiss1 gene expression across the pubertal period, yet whether just one or both (or neither) population is needed for puberty to occur has not been determined. Here, we sought to tease out the role—if any—of ARC and AVPV Kiss1 neurons in the pubertal onset process. Since ARC Kiss1 neurons are abundant in both sexes and drive pulsatile GnRH secretion in adulthood, we hypothesized that ARC Kiss1 neurons are necessary for normal puberty onset and, conversely, that AVPV Kiss1 neurons are not sufficient on their own to induce normal puberty. To test this hypothesis, we used a Cre-specific diphtheria toxin approach to ablate just ARC Kiss1 neurons in juvenile mice (~ 2 weeks old) while leaving AVPV Kiss1 neurons intact. Preliminary data thus far indicates that site specific ablation of just ARC Kiss1 neurons during the juvenile period significantly delays puberty onset in both sexes, as measured by vaginal opening, first estrous, and preputial separation. In addition, selective ARC Kiss1 neuron ablation in juvenile life diminishes pulsatile LH secretion levels measured in adulthood, but does not alter LH surge generation in adult females. These preliminary findings empirically demonstrate that, in mice, ARC Kiss1 neurons are required for proper activation of the reproductive axis during puberty but not the LH surge in adulthood, and AVPV Kiss1 neurons are not sufficient to trigger normal pubertal onset.

Central injection of neuropeptide Y modulates sexual behavior in male rats: interaction with GnRH and kisspeptin/neurokinin B/dynorphin

Aims A number of studies have shown that neuropeptide Y (NPY) is considered to be one of the key regulators of hypothalamic-pituitary-gonadal (HPG) axis in the mammals. In addition, kisspeptin (encode by Kiss1 gene), neurokinin B (encode by Tac3 gene) and dynorphin (encode by Pdyn gene) (commonly known as KNDy secreting neurons) are a powerful upstream regulators of GnRH neuron in hypothalamus. Materials and Methods The present study aims to investigate the effects of the intracerebroventricular (icv) injection of NPY and BIBP3226 (NPY receptor antagonist (NPYRA)) on the male sexual behavioral. Additionally, in order to see whether NPY signals can be relayed through the pathway of kisspeptin/neurokinin B/dynorphin, the gene expression of these peptides along with Gnrh1 gene in the hypothalamus were measured. Results The icv injection of NPY decreased the latencies and increase the frequencies of sexual parameters of the male rats in a significant way. In this line, NPYRA antagonized the stimulative effects of NPY. Moreover, data from real-time quantitative PCR indicated that injection of NPY significantly increased the gene expression of Gnrh1, Kiss1 and Tac3 and decrease the Pdyn while treatment with NPYRA controlled the modulative effects of NPY on these gene expression. Conclusions In conclusion based on the results of this study, NPY can exert its impacts on the sexual behavior of male rats via modulation of the KNDy secreting neurons as an interneural pathway to GnRH neurons.

The effects of daylight exposure on melatonin levels, Kiss1 expression, and melanoma formation in mice

AimTo determine how daylight exposure in mice affects melatonin protein expression in blood and Kiss1 gene expression in the hypothalamus. The second aim was to assess the relationship between skin cancer formation, daylight exposure, melatonin blood level, and kisspeptin gene expression level.MethodsNew-born mice (n = 96) were assigned into the blind group or daylight group. The blind group was raised in the dark and the daylight group was raised under 12 hours light/12 hours dark cycle for 17 weeks. At the end of the 11th week, melanoma cell line was inoculated to mice, and tumor growth was observed for 6 weeks. At the end of the experiment, melatonin level was measured from blood serum and Kiss1 expression from the hypothalamus.ResultsThe blind group had significantly higher melatonin and lower Kiss1 expression levels than the daylight group. Tumor volume was inversely proportional to melatonin levels and directly proportional to Kiss1 expression levels. Tumor growth speed was lower in the blind than in the daylight group.ConclusionMelatonin and Kiss1 were shown to be involved in tumor suppression. They were affected by daylight and were mutually affected by each other.

Effects of the Fertility Drugs Clomiphene Citrate and Letrozole on Kiss-1 Expression in Hypothalamic Kiss-1-Expressing Cell Models.

Clomiphene citrate (CC) and letrozole stimulate the hypothalamic-pituitary-ovarian axis and are used widely as oral fertility drugs to induce folliculogenesis. We examined whether these drugs increase Kiss-1 expression in hypothalamic cell models. We utilized two hypothalamic cell models, mHypoA-50 and mHypoA-55, which originated from Kiss-1 neurons in the anteroventral periventricular (AVPV) nucleus and arcuate (ARC) nucleus of the mouse hypothalamus, respectively. The cells were stimulated with CC or letrozole, after which Kiss-1 mRNA expression was determined. CC stimulated Kiss-1 gene expression in mHypoA-50 and mHypoA-55 cells. The basal expression of Kiss-1 was significantly increased in the presence of estradiol (E2) in mHypoA-50 cells, and the CC-induced increase in Kiss-1 expression was not observed in the presence of E2 in these cells. In contrast, E2 did not modify the basal expression of Kiss-1 in mHypoA-55 cells, and CC-induced Kiss-1 expression was still observed in the presence of E2. The significant increase in Kiss-1 gene expression in mHypoA-50 and mHypoA-55 cells was blunted in the presence of estrogen receptor antagonists. Aromatase was expressed in mHypoA-50 and mHypoA-55 cells. Letrozole, an aromatase inhibitor, increased Kiss-1 expression in mHypoA-55 ARC cells but not in mHypoA-50 AVPV cells. Although the basal expression of Kiss-1 was increased by E2, letrozole did not modulate Kiss-1 expression in mHypoA-50 cells. Letrozole-induced Kiss-1 gene expression in mHypoA-55 cells was not modulated in the presence of E2. The fertility drugs CC and letrozole modulated Kiss-1 expression in hypothalamic cell models.

The effect of intracerebroventricular administration of neuropeptide Y on reproductive axis function in the male Wistar rats: Involvement of hypothalamic KiSS1/GPR54 system.

Several studies have shown that neuropeptide Y (NPY) is considered to be one of the key regulators of the hypothalamic-pituitary-gonadal axis in the mammals. Also, kisspeptin is a powerful upstream regulator of gonadotropin-releasing hormone neurons in the hypothalamus. The present study aims to investigate the effects of the intracerebroventricular (ICV) injection of NPY and BIBP3226 (NPY receptor antagonist) on the reproductive axis (either hormonal or behavioral) of the male rats. Furthermore, to see whether NPY signals can be relayed through the pathway of KiSS1/GPR54, the gene expression of these peptides in the arcuate nucleus was measured. The ICV injection of NPY decreased the latencies and increased the frequencies of sexual parameters of the male rats in a significant way. Results obtained from LH and testosterone measurement showed that NPY had a significant increase in comparison with the control group. In this line, BIBP3226 antagonized the stimulative effects of NPY. Furthermore, data from real-time quantitative PCR showed that injection of NPY significantly increased the gene expression of KiSS1 and GPR54, while treatment with BIBP3226 controlled the stimulative effects of NPY on gene expression of KiSS1 and GPR54. Summing up, NPY can exert its impacts on the reproductive axis, this occurs at least partly through affecting KiSS1/GPR54 system.

Upregulation of Kiss-1 and Gpr54 Genes Expression in Pituitary of Male Rats Following the Central Administration of Neuropeptide Y

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.

Allelic Loss Of 1Q32.1 The Kiss-1 Metastasis Suppressor Gene Locus in Iraqi Patients with Breast Cancer

Experimental cell lines provide evidence on Kiss-1 gene as a regulator of metastasis in many kinds of cancers, including breast cancer. However, there is scarcity in data for kiss1 gene expression profile in many malignancies, and to date, no effort has been made to explore kiss-1 gene-associated microsatellite markers in many types of tumors, including breast cancer. The present study aims to investigate the microsatellite markers associated with Kiss-1 gene and the current loss of Heterozygosity LOH in Iraqi patients with breast cancer; this was further correlated with immunohistochemical Kiss-1 gene expression. One hundred and three breast carcinoma samples were collected after mastectomy. Kiss-1 gene expression was analyzed using immunostaining. Three microsatellite marker sites: SHGC-76112, SHGC-76186 intragenic, and SHGC-33412 in chromosome 1q32.1 were selected to define allelotyping of kiss-1 gene in paired DNA samples `from tumor cells and control blood cells of each patient. The loss of Kiss-1 gene expression was significantly correlated with the clinical tumor stage (p-value andGLT; 0.01). Loss of heterozygosity (LOH) occurs in 60 (60%) samples. Seven of the examined samples show LOH in two markers; none of the samples show LOH in the three markers. Seven samples show LOH for both intragenic markers (SHGC-76112 and SHGC-76186). The highest LOH percentage was 28%, which occurred within the intragenic microsatellite marker (SHGC-76186), and the lowest was 14% within the flanking region microsatellite marker (SHGC-33412). Interestingly, a statistically significant relationship was found between the LOH and Loss of Kiss-1 gene expression (p-value = 0.0005). This study convinced us to consider the vital role of this gene in the progression of the carcinoma in Iraqi patients with breast cancer.

Changes in expression of reproduction-related hormones in the brain and pituitary during early ovarian differentiation and development in the red spotted grouper Epinephelus akaara, with emphasis on FSHβ and LHβ

The brain-pituitary-gonadal (BPG) axis, an important endocrine system, is closely related to gonadal development in teleosts. This study aimed to investigate the regulation of reproduction-related hormones in the BPG axis during early ovarian differentiation and development from 30 to 160 days post hatching (dph) in the red spotted grouper. The immune signals of FSHβ and LHβ were detected by immunohistochemistry. kiss1, kiss2, gpr54, gnrh1, fshβ, and lhβ gene expression was analyzed using qRT-PCR. 17β-estradiol (E2) levels were analyzed by ELISA. The immune signals of FSHβ and LHβ were detected in the central, ventral, or marginal part of the proximal pars distalis area at 55, 80, 100, 120, and 160 dph, along with a few signals detected in the external border of the pars intermedia area at 55, 120, and 160 dph. As a result of histological observation, we determined that ovarian differentiation began at 80 dph and finished at 120 dph. At 30 dph before ovarian differentiation, only the FSHβ signal was detected but with weak reaction, suggesting the earlier appearance of FSHβ than LHβ after hatching. Comparison of the signal intensity and gene expression of FSHβ and LHβ indicated that LH had stronger signals and higher transcript levels at 80 dph while E2 levels also increased, suggesting that LH may play a more active role in the onset of ovarian differentiation. gnrh1 and the kisspeptin genes showed no clear changes, but gpr54 (kisspeptin receptor) significantly increased during the ovarian differentiation phase. These results suggest that the kisspeptin receptor GPR54 may be involved in ovarian differentiation in the red spotted grouper.

Role of RFRP-3 in the Regulation of Kiss-1 Gene Expression in the AVPV Hypothalamic Cell Model mHypoA-50.

Kisspeptin, encoded by the Kiss-1 gene, plays a crucial role in reproductive function by governing the hypothalamic-pituitary-gonadal axis. The recently established Kiss-1-expressing cell model mHypoA-50 displays characteristics of neuronal cells of the anteroventral periventricular (AVPV) region of the mouse hypothalamus. Because Kiss-1 gene expression in these cells is upregulated by estradiol (E2), mHypoA-50 cells are regarded as a valuable model for the study of Kiss-1-expressing neurons in the AVPV region. These cells also express RFamide-related peptide-3 (RFRP-3), a mammalian homolog of gonadotropin inhibitory hormone. The RFRP-3 expression in mHypoA-50 cells was increased by melatonin stimulation. In addition, E2 stimulation increased RFRP-3 expression in these cells. Treatment of the mHypoA-50 cells with exogenous RFRP-3 resulted in the increase of Kiss-1 messenger RNA expression within the cells; however, RFRP-3 did not modify gonadotropin-releasing hormone or kisspeptin-induced Kiss-1 gene expression in these cells. In addition, we found that RFRP-3 stimulation increased the expression of corticotropin-releasing hormone, which may be involved in E2-induced positive feedback in mHypoA-50 cells. Our observations suggest that RFRP-3 might be involved in positive feedback regulation by directly or indirectly increasing Kiss-1 gene expression.

Estradiol Enables Chronic Corticosterone to Inhibit Pulsatile Luteinizing Hormone Secretion and Suppress Kiss1 Neuronal Activation in Female Mice

Introduction: Two common responses to stress include elevated circulating glucocorticoids and impaired luteinizing hormone (LH) secretion. We have previously shown that a chronic stress level of corticosterone can impair ovarian cyclicity in intact mice by preventing follicular-phase endocrine events. Objective: This study is aimed at investigating if corticosterone can disrupt LH pulses and whether estradiol is necessary for this inhibition. Methods: Our approach was to measure LH pulses prior to and following the administration of chronic corticosterone or cholesterol in ovariectomized (OVX) mice treated with or without estradiol, as well as assess changes in arcuate kisspeptin (Kiss1) neuronal activation, as determined by co-expression with c-Fos. Results: In OVX mice, a chronic 48 h elevation in corticosterone did not alter the pulsatile pattern of LH. In contrast, corticosterone induced a robust suppression of pulsatile LH secretion in mice treated with estradiol. This suppression represented a decrease in pulse frequency without a change in amplitude. We show that the majority of arcuate Kiss1 neurons contain glucocorticoid receptor, revealing a potential site of corticosterone action. Although arcuate Kiss1 and Tac2 gene expression did not change in response to corticosterone, arcuate Kiss1 neuronal activation was significantly reduced by chronic corticosterone, but only in mice treated with estradiol. Conclusions: Collectively, these data demonstrate that chronic corticosterone inhibits LH pulse frequency and reduces Kiss1 neuronal activation in female mice, both in an estradiol-dependent manner. Our findings support the possibility that enhanced sensitivity to glucocorticoids, due to ovarian steroid milieu, may contribute to reproductive impairment associated with stress or pathophysiologic conditions of elevated glucocorticoids.

Exogenous kisspeptin (kp-10) resumes cyclicity in postpartum anestrus mithun cows

Present study was conducted to assess the effect of exogenous kisspeptin administration on estrus induction, Kiss1gene expression, endocrinological profiles and follicular development in post partum (PP) anestrus mithun cows. Animals who failed to resume cyclicity after day 90–100 of parturition were selected. Experimental cows were examined thoroughly through per-rectal as well as ultrasonograpic examination to confirm the anestrous status. PP anestrous healthy mithun cows (12), aged 5–6 years (body condition score: 5–6 of 10) were selected with uniform anestrus status and randomly divided into 2 groups namely treatment (Gr I) and control (Gr II), each group consist 6 cows. Anestrus cows in Gr 1 were injected with kisspeptin @ 1.30 μg per kg body weight at 3 day interval for 21 days after 90–100 days of post parturition whereas in control group, normal saline was injected as placebo. Blood samples were collected on the days of injection and at estrus in both the groups. Trans-rectal ultrasonography was done at 3 days interval till onset of estrus and ovulation to study the follicular development. Exogenous kisspeptin administration caused significantly early resumption of cyclicity in treatment as compared to control (24.64±10.43 vs 66.56±14.66 days) and significantly increased kiss1 and GPR54 mRNA expression in treatment as compared to control on the day of estrus (1.943±0.29 vs 0.424±0.062 and 1.84±0.31 vs 0.416±0.082, respectively). Similarly, circulating level of estradiol and follicle stimulating hormone (FSH) increased gradually after exogenous administration of kisspeptin, which reached peak on the day of estrus in treatment group (25.36±1.27 pg/ml and 15.65±1.22 ng/ml, respectively) whereas no significant difference was observed between days of treatment in control group except on the day of estrus (11.29±1.76 pg/ml and 9.86±1.06 ng/ml, respectively). Level of estradiol and FSH on the day of estrus was significantly higher in treatment as compared to control whereas non-significant difference was observed in plasma progesterone concentration. Number of medium and large follicles increased in treatment whereas only small follicles were observed in control group. Improved endocrinological profiles, follicle development and kiss gene profiles in post partum anestrous mithun cows following exogenous kisspeptin indicates that kisspeptin inducted or resumed the cyclicity in early.

Role of activin, follistatin, and inhibin in the regulation of Kiss-1 gene expression in hypothalamic cell models†.

Kisspeptin (encoded by the Kiss-1 gene) in the arcuate nucleus (ARC) of the hypothalamus governs the hypothalamic-pituitary-gonadal (HPG) axis by regulating pulsatile release of gonadotropin-releasing hormone (GnRH). Meanwhile, kisspeptin in the anteroventral periventricular nucleus (AVPV) region has been implicated in estradiol (E2)-induced GnRH surges. Kiss-1-expressing cell model mHypoA-55 exhibits characteristics of Kiss-1 neurons in the ARC region. On the other hand, Kiss-1 expressing mHypoA-50 cells originate from the AVPV region. In the mHypoA-55 ARC cells, activin significantly increased Kiss-1 gene expression. Follistatin alone reduced Kiss-1 expression within these cells. Interestingly, activin-induced Kiss-1 gene expression was completely abolished by follistatin. Inhibin A, but not inhibin B reduced Kiss-1 expression. Activin-increased Kiss-1 expression was also abolished by inhibin A. Pretreatment of the cells with follistatin or inhibin A significantly inhibited kisspeptin- or GnRH-induced Kiss-1 gene expression in mHypoA-55 cells. In contrast, in the mHypoA-50 AVPV cell model, activin, follistatin, and inhibin A did not modulate Kiss-1 gene expression. The subunits that compose activin and inhibin, as well as follistatin were expressed in both mHypoA-55 and mHypoA-50 cells. Expression of inhibin βA and βB subunits and follistatin was much higher in mHypoA-55 ARC cells. Furthermore, we found that expression of the inhibin α subunit and follistatin genes was modulated in the presence of E2 in mHypoA-55 ARC cells. The results of this study suggest that activin, follistatin, and inhibin A within the ARC region participate in the regulation of the HPG axis under the influence of E2.