共查询到20条相似文献,搜索用时 31 毫秒
1.
M. Sakakibara C. Deura S. Minabe Y. Iwata Y. Uenoyama K.‐I. Maeda H. Tsukamura 《Journal of neuroendocrinology》2013,25(3):251-259
Female rats show a gonadotrophin‐releasing hormone (GnRH)/luteinising hormone (LH) surge in the presence of a preovulatory level of oestrogen, whereas males do not because of brain defeminisation during the developmental period by perinatal oestrogen converted from androgen. The present study aimed to identify the site(s) of oestrogen action and the critical period for defeminising the mechanism regulating the GnRH/LH surge. Animals given perinatal treatments, such as steroidal manipulations, brain local implantation of oestradiol (E2) or administration of an NMDA antagonist, were examined for their ability to show an E2‐induced LH surge at adulthood. Lordosis behaviour was examined to compare the mechanisms defeminising the GnRH/LH surge and sexual behaviour. A single s.c. oestradiol‐benzoate administration on either the day before birth (E21), the day of birth (D0) or day 5 (D5) postpartum completely abolished the E2‐induced LH surge at adulthood in female rats, although the same treatment did not inhibit lordosis. Perinatal castration on E21 or D0 partially rescued the E2‐induced LH surge in genetically male rats, whereas castration from E21 to D5 totally rescued lordosis. Neonatal E2 implantation in the anterior hypothalamus including the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) abolished the E2‐induced LH surge in female rats, whereas E2 implantation in the mid and posterior hypothalamic regions had no inhibitory effect on the LH surge. Lordosis was not affected by neonatal E2 implantation in any hypothalamic regions. In male rats, neonatal NMDA antagonist treatment rescued lordosis but not the LH surge. Taken together, these results suggest that an anterior hypothalamic region such as the AVPV/POA region is a perinatal site of oestrogen action where the GnRH/LH regulating system is defeminised to abolish the oestrogen‐induced surge. The mechanism for defeminisation of the GnRH/LH surge system might be different from that of sexual behaviour, in terms of the site(s) of oestrogen action and critical period, as well as the neurotransmitter system involved. 相似文献
2.
Lack of Pulse and Surge Modes and Glutamatergic Stimulation of Luteinising Hormone Release in Kiss1 Knockout Rats 总被引:2,自引:0,他引:2 下载免费PDF全文
Y. Hayakawa K. Ikegami Y. Watanabe C. Deura S. Minabe J. Tomikawa T. Goto N. Ieda N. Inoue M. Sanbo C. Tamura M. Hirabayashi K.‐I. Maeda H. Tsukamura 《Journal of neuroendocrinology》2015,27(3):187-197
Kisspeptin, encoded by the Kiss1 gene, has attracted attention as a key candidate neuropeptide in controlling puberty and reproduction via regulation of gonadotrophin‐releasing hormone (GnRH) secretion in mammals. Pioneer studies with Kiss1 or its cognate receptor Gpr54 knockout (KO) mice showed the indispensable role of kisspeptin‐GPR54 signalling in the control of animal reproduction, although detailed analyses of gonadotrophin secretion, especially pulsatile and surge‐mode of luteinising hormone (LH) secretion, were limited. Thus, in the present study, we have generated Kiss1 KO rats aiming to evaluate a key role of kisspeptin in governing reproduction via pulse and surge modes of GnRH/LH secretion. Kiss1 KO male and female rats showed a complete suppression of pulsatile LH secretion, which is responsible for folliculogenesis and spermatogenesis, and an absence of puberty and atrophic gonads. Kiss1 KO female rats showed no spontaneous LH/follicle‐stimulating hormone surge and an oestrogen‐induced LH surge, suggesting that the GnRH surge generation system, which is responsible for ovulation, does not function without kisspeptin. Furthermore, challenge of major stimulatory neurotransmitters, such as monosodium glutamate, NMDA and norepinephrine, failed to stimulate LH secretion in Kiss1 KO rats, albeit they stimulated LH release in wild‐type controls. Taken together, the results of the present study confirm that kisspeptin plays an indispensable role in generating two modes (pulse and surge) of GnRH/gonadotrophin secretion to regulate puberty onset and normal reproductive performance. In addition, the present study suggests that kisspeptin neurones play a critical role as a hub integrating major stimulatory neural inputs to GnRH neurones, using newly established Kiss1 KO rats, which serve as a useful model for detailed analysis of hormonal profiles. 相似文献
3.
Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice 下载免费PDF全文
D. A. Adekunbi X. F. Li G. Lass K. Shetty O. A. Adegoke S. H. Yeo W. H. Colledge S. L. Lightman K. T. O'Byrne 《Journal of neuroendocrinology》2018,30(3)
The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is, however, limited information available on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. The present study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and the anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss‐Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV‐hSyn‐DIO‐hM3D(Gq)‐mCherry) targeted to the MePD, with subsequent activation by i.p. injection of clozapine‐N‐oxide (CNO). Socio‐sexual behaviours were assessed in a counter‐balanced fashion after i.p. injection of either saline or CNO (5 mg kg‐1). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female, as well as the duration of social interaction. Additionally, after CNO injection, the mice appeared less anxious, as indicated by a longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline‐treated controls. These data indicate that DREADD‐induced activation of MePD kisspeptin neurones enhances both sexual partner preference in males and social interaction and also decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour. 相似文献
4.
Kisspeptin/Gpr54‐Independent Gonadotrophin‐Releasing Hormone Activity in Kiss1 and Gpr54 Mutant Mice
Y. M. Chan S. Broder‐Fingert K. M. Wong S. B. Seminara 《Journal of neuroendocrinology》2009,21(12):1015-1023
The kisspeptin/Gpr54 signalling pathway plays a critical role in reproduction by stimulating the secretion of gonadotrophin‐releasing hormone (GnRH), yet mice carrying mutations in Kiss1 (which encodes kisspeptin) or Gpr54 exhibit partial sexual maturation. For example, a proportion of female Kiss1?/? and Gpr54?/? mice exhibit vaginal oestrus, and some male Kiss1?/? and Gpr54?/? mice exhibit spermatogenesis. To characterise this partial sexual maturation, we examined the vaginal cytology of female Kiss1?/? and Gpr54?/? mice over time. Almost all mutant mice eventually enter oestrus, and then spontaneously transition from oestrus to dioestrus and back to oestrus again. These transitions are not associated with ovulation, and the frequency of these transitions increases with age. The oestrus exhibited by female Kiss1?/? and Gpr54?/? mice was disrupted by the administration of the competitive GnRH antagonist acyline, which also resulted in lower uterine weights and, in Kiss1?/? mice, lower serum follicle‐stimulating hormone (FSH) and luteinising hormone (LH) concentrations. Similarly, male Kiss1?/? and Gpr54?/? mice treated with acyline had smaller testicular sizes and an absence of mature sperm. In addition to examining intact Kiss1?/? and Gpr54?/? mice, we also assessed the effects of acyline on gonadotrophin concentrations in gonadectomised mice. Gonadectomy resulted in a significant increase in serum FSH concentrations in male Gpr54?/? and Kiss1?/? mice. Acyline administration to gonadectomised Kiss1?/? and Gpr54?/? male mice lowered serum FSH and LH concentrations significantly. By contrast to males, gonadectomy did not result in significant gonadotrophin changes in female Kiss1?/? and Gpr54?/? mice, but acyline administration was followed by a decrease in LH concentrations. These results demonstrate that, although kisspeptin signalling is critical for the high levels of GnRH activity required for normal sexual maturation and for ovulation, Kiss1?/? and Gpr54?/? mice retain some degree of GnRH activity. This GnRH activity is sufficient to produce significant effects on vaginal cytology and uterine weights in female mice and on spermatogenesis and testicular weights in male mice. 相似文献
5.
M. C. Poling J. H. Quennell G. M. Anderson A. S. Kauffman 《Journal of neuroendocrinology》2013,25(10):876-886
The neuropeptides kisspeptin (encoded by Kiss1) and RFamide‐related peptide‐3 (also known as GnIH; encoded by Rfrp) are potent stimulators and inhibitors, respectively, of reproduction. Whether kisspeptin or RFRP‐3 might act directly on each other's neuronal populations to indirectly modulate reproductive status is unknown. To examine possible interconnectivity of the kisspeptin and RFRP‐3 systems, we performed double‐label in situ hybridisation (ISH) for the RFRP‐3 receptors, Gpr147 and Gpr74, in hypothalamic Kiss1 neurones of adult male and female mice, as well as double‐label ISH for the kisspeptin receptor, Kiss1r, in Rfrp‐expressing neurones of the hypothalamic dorsal‐medial nucleus (DMN). Only a very small proportion (5‐10%) of Kiss1 neurones of the anteroventral periventricular region expressed Gpr147 or Gpr74 in either sex, whereas higher co‐expression (approximately 25%) existed in Kiss1 neurones in the arcuate nucleus. Thus, RFRP‐3 could signal to a small, primarily arcuate, subset of Kiss1 neurones, a conclusion supported by the finding of approximately 35% of arcuate kisspeptin cells receiving RFRP‐3‐immunoreactive fibre contacts. By contrast to the former situation, no Rfrp neurones co‐expressed Kiss1r in either sex, and Tacr3, the receptor for neurokinin B (NKB; a neuropeptide co‐expressed with arcuate kisspeptin neurones) was found in <10% of Rfrp neurones. Moreover, kisspeptin‐immunoreactive fibres did not readily appose RFRP‐3 cells in either sex, further excluding the likelihood that kisspeptin neurones directly communicate to RFRP‐3 neurones. Lastly, despite abundant NKB in the DMN region where RFRP‐3 soma reside, NKB was not co‐expressed in the majority of Rfrp neurones. Our results suggest that RFRP‐3 may modulate a small proportion of kisspeptin‐producing neurones in mice, particularly in the arcuate nucleus, whereas kisspeptin neurones are unlikely to have any direct reciprocal actions on RFRP‐3 neurones. 相似文献
6.
Characterisation of Kiss1r (Gpr54)‐Expressing Neurones in the Arcuate Nucleus of the Female Rat Hypothalamus 下载免费PDF全文
Kisspeptin is essential in reproduction and acts by stimulating neurones expressing gonadotrophin‐releasing hormone (GnRH). Recent studies suggest that kisspeptin has multiple roles in the modulation of neuronal circuits in systems outside the hypothalamic‐pituitary‐gonadal axis. Our recent research using in situ hybridisation (ISH) clarified the histological distribution of Kiss1r (Gpr54)‐expressing neurones in the rat brain that were presumed to be putative targets of kisspeptin. The arcuate nucleus (ARN) of the hypothalamus is one of the brain regions in which Kiss1r expression in non‐GnRH neurones is prominent. However, the characteristics of Kiss1r‐expressing neurones in the ARN remain unclear. The present study aimed to determine the neurochemical characteristics of Kiss1r‐expressing neurones in the ARN using ISH and immunofluorescence. We revealed that the majority (approximately 63%) of Kiss1r‐expressing neurones in the ARN were pro‐opiomelanocortin (POMC) neurones, which have an anorexic effect in mammals. Additionally, a few Kiss1r‐expressing neurones in the dorsal ARN are tuberoinfundibular dopamine (TIDA) neurones, which control milk production by inhibiting prolactin secretion from the anterior pituitary. TIDA neurones showed a relatively weak Kiss1r ISH signal compared to POMC neurones, as well as low co‐expression of Kiss1r (approximately 15%). We also examined the expression of Kiss1r in neuropeptide Y and kisspeptin neurones, which are reported to arise from POMC‐expressing progenitor cells during development. However, the vast majority of neuropeptide Y and kisspeptin neurones in the ARN did not express Kiss1r. These results suggest that kisspeptin may directly regulate energy homeostasis and milk production by modulating the activity of POMC and TIDA neurones, respectively. Our results provide an insight into the wide variety of roles that kisspeptin plays in homeostatic and neuroendocrine functions. 相似文献
7.
P. G. Morris S. Jackman L. C. Sinnett‐Smith M. Schacker C. Chen W. H. Colledge 《Journal of neuroendocrinology》2016,28(11)
Kisspeptin neuropeptides are encoded by the Kiss1 gene and play a critical role in the regulation of the mammalian reproductive axis. Kiss1 neurones are found in two locations in the rodent hypothalamus: one in the arcuate nucleus (ARC) and another in the RP3V region, which includes the anteroventral periventricular nucleus (AVPV). Detailed mapping of the fibre distribution of Kiss1 neurones will help with our understanding of the action of these neurones in other regions of the brain. We have generated a transgenic mouse in which the Kiss1 coding region is disrupted by a CRE‐GFP transgene so that expression of the CRE recombinase protein is driven from the Kiss1 promoter. As expected, mutant mice of both sexes are sterile with hypogonadotrophic hypogonadism and do not show the normal rise in luteinising hormone after gonadectomy. Mutant female mice do not develop mature Graafian follicles or form corpora lutea consistent with ovulatory failure. Mutant male mice have low blood testosterone levels and impaired spermatogenesis beyond the meiosis stage. Breeding Kiss‐CRE heterozygous mice with CRE‐activated tdTomato reporter mice allows fluorescence visualisation of Kiss1 neurones in brain slices. Approximately 80‐90% of tdTomato positive neurones in the ARC were co‐labelled with kisspeptin and expression of tdTomato in the AVPV region was sexually dimorphic, with higher expression in females than males. A small number of tdTomato‐labelled neurones was also found in other locations, including the lateral septum, the anterodorsal preoptic nucleus, the amygdala, the dorsomedial and ventromedial hypothalamic nuclei, the periaquaductal grey, and the mammillary nucleus. Three dimensional visualisation of Kiss1 neurones and fibres by CLARITY processing of whole brains showed an increase in ARC expression during puberty and higher numbers of Kiss1 neurones in the caudal region of the ARC compared to the rostral region. ARC Kiss1 neurones sent fibre projections to several hypothalamic regions, including rostrally to the periventricular and pre‐optic areas and to the lateral hypothalamus. 相似文献
8.
The Distribution of Kisspeptin (Kiss)1‐ and Kiss2‐Positive Neurones and Their Connections with Gonadotrophin‐Releasing Hormone‐3 Neurones in the Zebrafish Brain 下载免费PDF全文
Kisspeptin is a neuroendocrine hormone with a critical role in the activation of gonadotrophin‐releasing hormone (GnRH) neurones, which is vital for the onset of puberty in mammals. However, the functions of kisspeptin neurones in non‐mammalian vertebrates are not well understood. We have used transgenics to labell kisspeptin neurones (Kiss1 and Kiss2) with mCherry in zebrafish (Danio rerio). In kiss1:mCherry transgenic zebrafish, Kiss1 cells were located in the dorsomedial and ventromedial habenula, with their nerve fibres contributing to the fasciculus retroflexus and projecting to the ventral parts of the interpeduncular and raphe nuclei. In kiss2:mCherry zebrafish, Kiss2 cells were primarily located in the dorsal zone of the periventricular hypothalamus and, to a lesser extent, in the periventricular nucleus of the posterior tuberculum and the preoptic area. Kiss2 fibres formed a wide network projecting into the telencephalon, the mesencephalon, the hypothalamus and the pituitary. To study the relationship of kisspeptin neurones and GnRH3 neurones, these fish were crossed with gnrh3:EGFP zebrafish to obtain kiss1:mCherry/gnrh3:EGFP and kiss2:mCherry/gnrh3:EGFP double transgenic zebrafish. The GnRH3 fibres ascending to the habenula were closely associated with Kiss1 fibres projecting from the ventral habenula. On the other hand, GnRH3 fibres and Kiss2 fibres were adjacent but scarcely in contact with each other in the telencephalon and the hypothalamus. The Kiss2 and GnRH3 fibres in the ventral hypothalamus projected into the pituitary via the pituitary stalk. In the pituitary, Kiss2 fibres were directly in contact with GnRH3 fibres in the pars distalis. These results reveal the pattern of kisspeptin neurones and their connections with GnRH3 neurones in the brain, suggesting distinct mechanisms for Kiss1 and Kiss2 in regulating reproductive events in zebrafish. 相似文献
9.
Enhancement of the luteinising hormone surge by male olfactory signals is associated with anteroventral periventricular Kiss1 cell activation in female rats 下载免费PDF全文
Y. Watanabe K. Ikegami R. Ishigaki N. Ieda Y. Uenoyama K. I. Maeda H. Tsukamura N. Inoue 《Journal of neuroendocrinology》2017,29(8)
Olfactory stimuli play an important role in regulating reproductive functions in mammals. The present study investigated the effect of olfactory signals derived from male rats on kisspeptin neuronal activity and luteinising hormone (LH) secretion in female rats. Wistar‐Imamichi strain female rats were ovariectomised (OVX) and implanted with preovulatory levels of 17β‐oestradiol (E2). OVX+E2 rats were killed 1 hour after exposure to either: clean bedding, female‐soiled bedding or male‐soiled bedding. Dual staining for Kiss1 mRNA in situ hybridisation and c‐Fos immunohistochemistry revealed that the numbers of Kiss1‐expressing cells and c‐Fos‐immunopositive Kiss1‐expressing cells in the anteroventral periventricular nucleus (AVPV) were significantly higher in OVX+E2 rats exposed to male‐soiled bedding than those of the other groups. No significant difference was found with respect to the number of c‐Fos‐immunopositive Kiss1‐expressing cells in the arcuate nucleus and c‐Fos‐immunopositive Gnrh1‐expressing cells between the groups. The number of c‐Fos‐immunopositive cells was also significantly higher in the limbic system consisting of several nuclei, such as the bed nucleus of the stria terminalis, the cortical amygdala and the medial amygdala, in OVX+E2 rats exposed to male‐soiled bedding than the other groups. OVX+E2 rats exposed to male‐soiled bedding showed apparent LH surges, and the peak of the LH surge and area under the curve of LH concentrations in the OVX+E2 group were significantly higher than those of the other two groups. These results suggest that olfactory signals derived from male rats activate AVPV kisspeptin neurones, likely via the limbic system, resulting in enhancement of the peak of the LH surge in female rats. Taken together, the results of the present study suggests that AVPV kisspeptin neurones are a target of olfactory signals to modulate LH release in female rats. 相似文献
10.
A. S. Kauffman 《Journal of neuroendocrinology》2010,22(7):682-691
The brains of males and females differ anatomically and physiologically, including sex differences in neurone size or number, synapse morphology and specific patterns of gene expression. Brain sex differences may underlie critical sex differences in physiology or behaviour, including several aspects of reproduction, such as the timing of sexual maturation (earlier in females than males) and the ability to generate a preovulatory gonadotrophin surge (in females only). The reproductive axis is controlled by afferent pathways that converge upon forebrain gonadotrophin‐releasing hormone (GnRH) neurones, but GnRH neurones are not sexually dimorphic. Although most reproductive sex differences probably reflect sex differences in the upstream circuits and factors that regulate GnRH secretion, the key sexually‐dimorphic factors that influence reproductive status have remained poorly defined. The recently‐identified neuropeptide kisspeptin, encoded by the Kiss1 gene, is an important regulator of GnRH secretion, and Kiss1 neurones in rodents are sexually dimorphic in specific hypothalamic populations, including the anteroventral periventricular nucleus–periventricular nucleus continuum (AVPV/PeN) and the arcuate nucleus (ARC). In the adult AVPV/PeN, Kiss1 neurones are more abundant in females than males, representing a sex difference that is regulated by oestradiol signalling during critical periods of postnatal and pubertal development. By contrast, Kiss1 neurones in the ARC are not sexually differentiated in adult rodents but, in mice, the regulation of ARC Kiss1 cells by gonadal hormone‐independent factors is sexually dimorphic during prepubertal development. These various sex differences in hypothalamic Kiss1 neurones may relate to known sex differences in reproductive physiology, such as puberty onset and positive feedback. 相似文献
11.
12.
The Luteinising Hormone Surge‐Generating System is Functional in Male Goats as in Females: Involvement of Kisspeptin Neurones in the Medial Preoptic Area 下载免费PDF全文
F. Matsuda K. Nakatsukasa Y. Suetomi Y. Naniwa D. Ito N. Inoue Y. Wakabayashi H. Okamura K.‐I. Maeda Y. Uenoyama H. Tsukamura S. Ohkura 《Journal of neuroendocrinology》2015,27(1):57-65
A luteinising hormone (LH) surge is fundamental to the induction of ovulation in mammalian females. The administration of a preovulatory level of oestrogen evokes an LH surge in ovariectomised females, whereas the response to oestrogen in castrated males differs among species; namely, the LH surge‐generating system is sexually differentiated in some species (e.g. rodents and sheep) but not in others (e.g. primates). In the present study, we aimed to determine whether there is a functional LH surge‐generating system in male goats, and whether hypothalamic kisspeptin neurones in male goats are involved in the regulation of surge‐like LH secretion. By i.v. infusion of oestradiol (E2; 6 μg/h) for 16 h, a surge‐like LH increase occurred in both castrated male and ovariectomised female goats, although the mean peak LH concentration was lower and the mean peak of the LH surge was later in males compared to females. Dual staining with KISS1 in situ hybridisation and c‐Fos immunohistochemistry revealed that E2 treatment significantly increased c‐Fos expression in the medial preoptic area (mPOA) KISS1 cells in castrated males, as well as ovariectomised females. By contrast, dual‐labelled cells were scarcely detected in the arcuate nucleus (ARC) after E2 treatment in both sexes. These data suggest that kisspeptin neurones in the mPOA, but not those in the ARC, are involved in the induction of surge‐like LH secretion in both male and female goats. In summary, our data show that the mechanism that initiates the LH surge in response to oestrogen, the mPOA kisspeptin neurones, is functional in male goats. Thus, sexual differentiation of the LH surge‐generating system would not be applicable to goats. 相似文献
13.
Galanin‐like peptide (GALP) is a known mediator of metabolism and reproduction; however, the role that GALP plays in the onset of puberty is unknown. First, we tested the hypothesis that central GALP administration could rescue puberty in food‐restricted weanling rats. GALP treatment in food‐restricted rats of both sexes rescued the timing of the onset of puberty to that seen in ad lib. fed controls. Second, we tested whether GALP translation knocked‐down in ad lib. fed, prepubertal rats would alter the timing of puberty. Knock‐down females, but not males, showed a significant (P < 0.01) delay in the onset of puberty compared to controls. Third, we sought evidence that the role of GALP in pubertal onset is mediated by the kisspeptin system. In situ hybridisation analyses showed a significant (P < 0.01) reduction in Kiss1 mRNA within the hypothalamic arcuate nucleus in food‐restricted rats compared to ad lib. fed controls and this reduction was prevented with i.c.v. GALP administration. Furthermore, analyses of Fos‐immunoreactivity (‐IR) after i.c.v. GALP treatment did not elicit Fos‐IR within any kisspeptin neurones, nor are GALP and kisspeptin peptides or mRNA colocalised. These data demonstrate that hypothalamic GALP infusion maintained the onset of puberty in food‐restricted weanling rats, although probably not via direct innervation of kisspeptin neurones. 相似文献
14.
Gabriela Neubert da Silva Tatiana Zauer Curi Sara Emília Lima Tolouei Marcella Tapias Passoni Giovanna Beatriz Sari Hey Renata Marino Romano Anderson Joel Martino‐Andrade Paulo Roberto Dalsenter 《Journal of neuroendocrinology》2019,31(12)
Phthalates are found in different plastic materials, such as packaging, toys and medical devices. Some of these compounds are endocrine disruptors, comprising substances that are able to induce multiple hormonal disturbances and downstream developmental effects, including the disruption of androgen‐dependent differentiation of the male reproductive tract and changes in pathways that regulate hormone‐dependent behaviours. In a previous study, metabolites of diisopentyl phthalate (DiPeP), a potent anti‐androgenic phthalate, were found in the urine of Brazilian pregnant women. Therefore, the present study aimed to evaluate the effects of DiPeP exposure during critical developmental periods on behaviours controlled by sex hormones in rats. Pregnant Wistar rats were treated with DiPeP (1, 10 or 100 mg kg day‐1) or canola oil by oral gavage between gestational day 10 and post‐natal day (PND) 21. Male offspring were tested in a behavioural battery, including the elevated plus maze task, play behaviour, partner preference and sexual behaviour. After the behavioural tests, the hypothalamus and pituitary of these animals were removed on PND 60‐65 and PND 145‐160 to quantify gene expression for aromatase, androgen receptor (Ar) and oestrogen receptors α (Esr1) and β (Esr2). Male rats exposed to 1 and 10 mg kg day‐1 DiPeP displayed no preference for the female stimulus rat in the partner preference test and 1 mg kg day‐1 DiPeP rats also showed a significant increase in mount and penetration latencies when mated with receptive females. A decrease in pituitary Esr1 expression was observed in all DiPeP treated groups regardless of age. A reduction in hypothalamic Esr1 expression in rats exposed to 10 mg kg day‐1 DiPeP was also observed. No significant changes were found with respect to Ar, Esr2 and aromatase expression in the hypothalamus. These results suggest that DiPeP exposure during critical windows of development in rats may induce changes in behaviours related to mating and the sexual motivation of males. 相似文献
15.
Release of gonadotropins in adult rodents is sex specific and dependent upon kisspeptin (Kiss1) neurons. This crucial pathway within the hypothalamic-pituitary-gonadal (HPG) axis is profoundly influenced by neonatal estrogens, which induce a male-like phenotype. Classically, estrogen activity is mediated via the estrogen receptors α and β (ERα and ERβ), but the relative roles each plays in organizing the sex-specific ontogeny of kisspeptin signaling pathways remain unresolved. Thus, the present study used in situ hybridization histochemistry (ISHH) to map the temporal and sexually dimorphic neonatal mRNA expression profiles of ERα, ERβ, and Kiss1 in the anterioventral periventricular nucleus (AVPV), medial preoptic area (MPOA), ventromedial nucleus (VMN), and arcuate nucleus (ARC), all regions critical for kisspeptin regulation of gonadotropin secretion. In general, females had higher levels of ERα, in all regions examined, a sex difference that persisted until postnatal day (PND) 19 except in the ARC. Males had significantly more ERβ expression in the AVPV at birth, but this sex difference was lost and then re-emerged on PND 19, with females having more than males. VMN ERβ levels were higher in females until PND 19. Kiss1 was not detectable until PND 11 in the anterior hypothalamus, but expression levels were equivalent at birth in the ARC. By PND 2, ARC ERα and Kiss1 levels were abundant, sexually dimorphic (higher in females), and, respectively, showed a U- and a bell-shaped pattern with age. Sex differences in ARC Kiss1 expression provide evidence that Kiss1 may play a role in the sexual dimorphic organization of the neonatal brain. These detailed profiles of neonatal Kiss1 and ERs mRNA levels will help elucidate the relative roles each plays in the sex-specific, estrogen-dependent organization of gonadotropin signaling pathways. 相似文献
16.
17.
Reproductive status‐dependent kisspeptin and RFamide‐related peptide (Rfrp) gene expression in female Damaraland mole‐rats 下载免费PDF全文
Damaraland mole rats (Fukomys damarensis) are cooperatively breeding, subterranean mammals that exhibit a high reproductive skew. Reproduction is monopolised by the dominant female of the group, whereas subordinates are physiologically suppressed to the extent that they are anovulatory. In these latter animals, it is assumed that normal gonadotropin‐releasing hormone secretion from the hypothalamus is disrupted. The RFamide peptides kisspeptin (Kiss1) and RFamide‐related peptide‐3 (RFRP‐3) are considered as potent regulators of gonadotropin release. To assess whether these neuropeptides are involved in the mechanism of reproductive suppression, we investigated the distribution and gene expression of Kiss1 and Rfrp by means of in situ hybridisation in wild‐caught female Damaraland mole‐rats with different reproductive status. In both reproductive phenotypes, substantial Kiss1 expression was found in the arcuate nucleus and only few Kiss1‐expressing cells were detected in the anteroventral periventricular nucleus (AVPV), potentially as a result of low circulating oestradiol concentrations in breeding and nonbreeding females. Rfrp gene expression occurred in the dorsomedial nucleus, the paraventricular nucleus and the periventricular nucleus. While in female breeders and nonbreeders, plasma oestradiol levels were low and not significantly different, quantification of the hybridisation signal for both genes revealed significant differences in relation to reproductive status. Reproductively active females had more Kiss1‐expressing cells and a higher number of silver grains per cell in the arcuate nucleus compared to nonreproductive females. This difference was most pronounced in the caudal part of the nucleus. No such differences were found in the AVPV. Furthermore, breeding status was associated with a reduced number of Rfrp‐expressing cells in the anterior hypothalamus. This reproductive status‐dependent expression pattern of Kiss1 and Rfrp suggests that both neuropeptides play a role in the regulation of reproduction in Damaraland mole‐rats. Enhanced long‐term negative feedback effects of oestradiol could be responsible for the lower Kiss1 expression in the arcuate nucleus of reproductively suppressed females. 相似文献
18.
Unaltered Hypothalamic Metabolic Gene Expression in Kiss1r Knockout Mice Despite Obesity and Reduced Energy Expenditure 下载免费PDF全文
Julie‐Ann P. De Bond Kristen P. Tolson Chanond Nasamran Alexander S. Kauffman Jeremy T. Smith 《Journal of neuroendocrinology》2016,28(10)
Kisspeptin controls reproduction by stimulating gonadotrophin‐releasing hormone neurones via its receptor Kiss1r. Kiss1r is also expressed other brain areas and in peripheral tissues, suggesting additional nonreproductive roles. We recently determined that Kiss1r knockout (KO) mice develop an obese and diabetic phenotype. In the present study, we investigated whether Kiss1r KOs develop this metabolic phenotype as a result of alterations in the expression of metabolic genes involved in the appetite regulating system of the hypothalamus, including neuropeptide Y (Npy) and pro‐opiomelanocortin (Pomc), as well as leptin receptor (Lepr), ghrelin receptor (Ghsr), and melanocortin receptors 3 and 4 (Mc3r, Mc4r). Body weights, leptin levels and hypothalamic gene expression were measured in both gonad‐intact and gonadectomised (GNX) mice at 8 and 20 weeks of age that had received either normal chow or a high‐fat diet. We detected significant increases in Pomc expression in gonad‐intact Kiss1r KO mice at 8 and 20 weeks, although there were no alterations in the other metabolic‐related genes. However, the Pomc increases appeared to reflect genotype differences in circulating sex steroids, because GNX wild‐type and Kiss1r KO mice exhibited similar Pomc levels, along with similar Npy levels. The altered Pomc gene expression in gonad‐intact Kiss1r KO mice is consistent with previous reports of reduced food intake in these mice and may serve to increase the anorexigenic drive, perhaps compensating for the obese state. However, the surprising overall lack of changes in any of the hypothalamic metabolic genes in GNX KO mice suggests that the aetiology of obesity in the absence of kisspeptin signalling may reflect peripheral rather than central metabolic impairments. 相似文献
19.
Noelia P. Di Giorgio Marianne Bizzozzero Hiriart Pablo N. Surkin Paula V. Lpez Nadia S. Bourguignon Vernica B. Dorfman Bernhard Bettler Carlos Libertun Victoria Lux‐Lantos 《Journal of neuroendocrinology》2019,31(8)
Female mice lacking GABAB receptors, GABAB1KO, show disrupted oestrous cycles, reduced pregnancies and increased hypothalamic Gnrh1 mRNA expression, whereas anteroventral periventricular/periventricular preoptic nucleus (AVPV/PeN) Kiss1 mRNA was not affected. In the present study, we characterise the important components of the gonadotrophic preovulatory surge, aiming to unravel the origin of this reproductive impairment. In GABAB1KO and wild‐type (WT) females, we determined: (i) hypothalamic oestrogen receptor (ER)α and β and aromatase mRNA and protein expression; (ii) ovulation index and oestrus serum follicle‐stimulating hormone (FSH) and pituitary Gnrh1r expression; (iii) in ovariectomised‐oestradiol valerate‐treated mice, we evaluated ex vivo hypothalamic gonadotrophin‐releasing hormone (GnRH) pulsatility in the presence/absence of kisspeptin (Kiss‐10, constant or pulsatile) and oestradiol (constant); and (iv) in ovariectomised‐oestradiol silastic capsule‐treated mice (proestrous‐like environment), we evaluated morning and evening kisspeptin neurone activation (c‐Fos+) and serum luteinising homrone (LH). In the medial basal hypothalamus of oestrus GABAB1KOs, aromatase and ERα mRNA and protein were increased, whereas ERβ was decreased. In GABAB1KOs, the ovulation index was decreased together with decreased first oestrus serum FSH and increased pituitary Gnrh1r mRNA. Under constant Kiss‐10 stimulation, hypothalamic GnRH pulse frequency did not vary, although GnRH mass/pulse was increased in GABAB1KOs. In WTs, pulsatile Kiss‐10 together with constant oestradiol significantly increased GnRH pulsatility, whereas, in GABAB1KOs, oestradiol alone increased GnRH pulsatility and this was reversed by pulsatile Kiss‐10 addition. In GABAB1KOs AVPV/PeN kisspeptin neurones were similarly activated (c‐Fos+) in the morning and evening, whereas WTs showed the expected, marked evening stimulation. LH correlated with activated kisspeptin cells in WT mice, whereas GABAB1KO mice showed high, similar LH levels both in the morning and evening. Taken together, all of these alterations point to impairment in the trigger of the preovulatory GnRH surge that entails the reproductive alterations described. 相似文献
20.
We recently reported that female aromatase knockout (ArKO) mice show deficits in sexual behaviour and a decreased population of kisspeptin‐immunoreactive neurones in the rostral periventricular area of the third ventricle (RP3V), resurrecting the question of whether oestradiol actively contributes to female‐typical sexual differentiation. To further address this question, we assessed the capacity of ArKO mice to generate a steroid‐induced luteinising hormone (LH) surge. Adult, gonadectomised wild‐type (WT) and ArKO mice were given silastic oestradiol implants s.c. and, 1 week later, received s.c. injections of either oestradiol benzoate (EB) followed by progesterone, EB alone, or no additional steroids to activate gonadotrophin‐releasing hormone (GnRH) neurones and generate an LH surge. Treatment with EB and progesterone induced significant Fos/GnRH double‐labelling and, consequently, an LH surge in female WT and in ArKO mice of both sexes but not in male WT mice. ArKO mice of both sexes had fewer cells expressing Kiss‐1 mRNA in the RP3V compared to female WT mice but had more Kiss‐1 mRNA‐expressing cells compared to WT males, reflecting an incomplete sexual differentiation of this system. To determine the number of cells expressing kisspeptin, the same experimental design was repeated in Experiment 2 with the addition of groups of WT and ArKO mice that were given EB + progesterone and sacrificed 2 h before the expected LH surge. No differences were observed in the number of kisspeptin‐immunoreactive cells 2 h before and at the time of the LH surge. The finding that ArKO mice of both sexes have a competent LH surge system suggests that oestradiol has predominantly defeminising actions on the GnRH/LH surge system in males and that the steroid‐induced LH surge can occur in females even with a greatly reduced population of kisspeptin neurones in the RP3V. 相似文献