scholarly journals Grid1 Regulates the Onset of Puberty in Female Rats

2020 ◽  
Author(s):  
Jing Ye ◽  
Ping Qin ◽  
Hailing Li ◽  
Tiezhu Kang ◽  
Wenyu Si ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Female Rats ◽  
Mrna Levels ◽  
Vaginal Opening ◽  
Ionotropic Receptor ◽  
Delta Type ◽  
Periventricular Nucleus ◽  
Old Rats ◽  
Puberty Onset

Abstract The present study aimed to investigate whether Grid1, encoding the glutamate ionotropic receptor delta type subunit 1(GluD1), influences the onset of puberty in female rats. First, we detected the expression of Grid1 mRNA and its protein in the hypothalamus from infancy to puberty. Second, we evaluated the suppression of Grid1 expression by Lentivirus-Grid1 (LV-Grid1) in primary hypothalamus cells through measuring the expression level of Grid1. Finally, LV-Grid1 was intracerebroventricular injected (ICV) into 21-day-old rats and to investigate the effect of Grid1 suppression on puberty onset in vivo. Results showed that GluD1 immunoreactivity could be detected in the arcuate nucleus (ARC), paraventricular nucleus (PVN), and periventricular nucleus (PeN). Grid1 mRNA levels were the lowest at prepuberty. Treatment of hypothalamic neurons with LV-Grid1 decreased the mRNA expression levels of Grid1 and Rfrp-3 (encoding RFamide-related peptide 3, RFRP 3), but increased that of Gnrh (encoding gonadotropin-releasing hormone, GnRH). After 7 days of ICV LV-Grid1 into rats, the Grid1 mRNA was significantly reduced (by 46%), Gnrh mRNA expression was significantly increased, but Rfrp-3 mRNA levels were decreased. The time of rat vaginal opening (VO) was earlier in the LV-Grid1 group; the concentrations of luteinizing hormone (LH), estradiol (E2), and progesterone (P4) in serum were significantly increased; and the ovaries were significantly larger. Our study revealed that Grid1 affects the onset of puberty by regulating the level of GnRH and RFRP3.

scholarly journals Early Metabolic Programming of Puberty Onset: Impact of Changes in Postnatal Feeding and Rearing Conditions on the Timing of Puberty and Development of the Hypothalamic Kisspeptin System

Endocrinology ◽  
2011 ◽  
Vol 152 (9) ◽  
pp. 3396-3408 ◽  
Author(s):  
Juan M. Castellano ◽  
Agnete H. Bentsen ◽  
Miguel A. Sánchez-Garrido ◽  
Francisco Ruiz-Pino ◽  
Magdalena Romero ◽  
...  
Keyword(s):  
Body Weight ◽  
Metabolic Disorders ◽  
Arcuate Nucleus ◽  
Female Rats ◽  
Mrna Levels ◽  
Vaginal Opening ◽  
Timing Of Puberty ◽  
Puberty Onset ◽  
Periventricular Area ◽  
Underlying Mechanisms

Kiss1 neurons have recently emerged as a putative conduit for the metabolic gating of reproduction, with leptin being a regulator of hypothalamic Kiss1 expression. Early perturbations of the nutritional status are known to predispose to different metabolic disorders later in life and to alter the timing of puberty; however, the potential underlying mechanisms remain poorly defined. Here we report how changes in the pattern of postnatal feeding affect the onset of puberty and evaluate key hormonal and neuropeptide [Kiss1/kisspeptin (Kp)] alterations linked to these early nutritional manipulations. Female rats were raised in litters of different sizes: small (four pups per dam: overfeeding), normal (12 pups per dam), and large litters (20 pups per litter: underfeeding). Postnatal overfeeding resulted in persistently increased body weight and earlier age of vaginal opening, as an external sign of puberty, together with higher levels of leptin and hypothalamic Kiss1 mRNA. Conversely, postnatal underfeeding caused a persistent reduction in body weight, lower ovarian and uterus weights, and delayed vaginal opening, changes that were paralleled by a decrease in leptin and Kiss1 mRNA levels. Kisspeptin-52 immunoreactivity (Kp-IR) in the hypothalamus displayed similar patterns, with lower numbers of Kp-IR neurons in the arcuate nucleus of postnatally underfed animals, and a trend for increased Kp-positive fibers in the periventricular area of early overfed rats. Yet, gonadotropin responses to Kp at puberty were similar in all groups, except for enhanced responsiveness to low doses of Kp-10 in postnatally underfed rats. In conclusion, our data document that the timing of puberty is sensitive to both overfeeding and subnutrition during early (postnatal) periods and suggest that alterations in hypothalamic expression of Kiss1/kisspeptin may underlie at least part of such programming phenomenon.

scholarly journals Downregulation of TTF1 in the rat hypothalamic ARC or AVPV nucleus inhibits Kiss1 and GnRH expression, leading to puberty delay

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shaolian Zang ◽  
Xiaoqin Yin ◽  
Pin Li
Keyword(s):  
Pubertal Development ◽  
Gonad Development ◽  
Gene Promoter ◽  
Female Rats ◽  
Luciferase Reporter ◽  
Vaginal Opening ◽  
Early Puberty ◽  
Puberty Onset

Abstract Background TTF1 is a transcription factor that is expressed in the hypothalamus after birth and plays crucial roles in pubertal development. TTF1 may regulate the expression of the Kiss1 gene, which may drive puberty onset in the hypothalamic arcuate (ARC) and anterior ventral paraventricular (AVPV) nuclei. Methods A dual-luciferase reporter assay was used to detect binding between TTF1 and the Kiss1 gene promoter. To investigate the effects of TTF1, we modified TTF1 expression in cell lines and in the ARC or AVPV nucleus of 21-day-old female rats via lentivirus infection. TTF1 and other puberty onset-related genes were detected by qRT-PCR and western blot analyses. Results The in vitro data indicated that TTF1 knockdown (KD) significantly reduced Kiss1 and GnRH expression. Overexpression (OE) of TTF1 promoted Kiss1 expression. In vivo, the expression of Kiss1 and GnRH decreased significantly in the rats with hypothalamic ARC- or AVPV-specific TTF1 KD. The TTF1-KD rats showed vaginal opening delay. H&E staining revealed that the corpus luteum was obviously reduced at the early puberty and adult stages in the rats with ARC- or AVPV-specific TTF1 KD. Conclusion TTF1 bound to the promoter of the Kiss1 gene and enhanced its expression. For 21-day-old female rats, decreased TTF1 in the hypothalamic ARC or AVPV nucleus resulted in delayed vaginal opening and ovarian abnormalities. These observations suggested that TTF1 regulates puberty onset by promoting the expression of Kiss1 and plays an important role in gonad development.

scholarly journals The Mammalian Target of Rapamycin as Novel Central Regulator of Puberty Onset via Modulation of Hypothalamic Kiss1 System

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5016-5026 ◽  
Author(s):  
J. Roa ◽  
D. Garcia-Galiano ◽  
L. Varela ◽  
M. A. Sánchez-Garrido ◽  
R. Pineda ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Female Rats ◽  
Target Of Rapamycin ◽  
Functional Coupling ◽  
Mrna Levels ◽  
Positive Effects ◽  
Puberty Onset ◽  
Lh Secretion

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that operates as sensor of cellular energy status and effector for its coupling to cell growth and proliferation. At the hypothalamic arcuate nucleus, mTOR signaling has been recently proposed as transducer for leptin effects on energy homeostasis and food intake. However, whether central mTOR also participates in metabolic regulation of fertility remains unexplored. We provide herein evidence for the involvement of mTOR in the control of puberty onset and LH secretion, likely via modulation of hypothalamic expression of Kiss1. Acute activation of mTOR by l-leucine stimulated LH secretion in pubertal female rats, whereas chronic l-leucine infusion partially rescued the state of hypogonadotropism induced by food restriction. Conversely, blockade of central mTOR signaling by rapamycin caused inhibition of the gonadotropic axis at puberty, with significantly delayed vaginal opening, decreased LH and estradiol levels, and ovarian and uterine atrophy. Inactivation of mTOR also blunted the positive effects of leptin on puberty onset in food-restricted females. Yet the GnRH/LH system retained their ability to respond to ovariectomy and kisspeptin-10 after sustained blockade of mTOR, ruling out the possibility of unspecific disruption of GnRH function by rapamycin. Finally, mTOR inactivation evoked a significant decrease of Kiss1 expression at the hypothalamus, with dramatic suppression of Kiss1 mRNA levels at the arcuate nucleus. Altogether our results unveil the role of central mTOR signaling in the control of puberty onset and gonadotropin secretion, a phenomenon that involves the regulation of Kiss1 and may contribute to the functional coupling between energy balance and gonadal activation and function.

GABAB receptor antagonism from birth to weaning permanently modifies Kiss1 expression in hypothalamus and gonads in mice

2021 ◽  
Author(s):  
Marianne Bizzozzero Hiriart ◽  
Noelia P. Di Giorgio ◽  
Carlos Libertun ◽  
Victoria A.R. Lux-Lantos
Keyword(s):  
Arcuate Nucleus ◽  
Gabab Receptor ◽  
Seminiferous Tubules ◽  
Testis Weight ◽  
Hpg Axis ◽  
Estrous Cycles ◽  
Amino Butyric Acid ◽  
Periventricular Nucleus ◽  
Puberty Onset ◽  
Ovulatory Follicles

Introduction: The kisspeptin gene Kiss1 is expressed in two hypothalamic areas: anteroventral periventricular nucleus/periventricular nucleus (AVPV/PeN) and arcuate nucleus (ARC), and also in gonads. Evidences suggest that gamma-amino butyric acid B receptors (GABAB) signaling can regulate Kiss1 expression. Here we inhibited GABAB signaling from PND2-PND21 and evaluated the hypothalamic-pituitary-gonadal (HPG) axis. Methods: BALB/c mice were treated on postnatal days 2-21 (PND2-PND21) with CGP55845 (GABAB antagonist), and evaluated in PND21 and adulthood: gene expression (qPCR) in hypothalamus and gonads, hormones by radioimmunoassay, gonad histochemistry (H&E), puberty onset, estrous cycles. Results: At PND21, CGP inhibited Kiss1 and Tac2 and increased Pdyn and Gabbr1 in the ARC of both sexes and decreased Th only in female AVPV/PeN. Serum follicle-stimulating hormone (FSH) and testis weight decreased in CGP-males and puberty onset was delayed. In adults, Kiss1, Tac2, Pdyn, Pgr, Cyp19a1, Gad1 were downregulated, while Gabbr1 was upregulated in the ARC of both sexes. In the AVPV/PeN, Kiss1, Th, Cyp19a1 and Pgr decreased while Gad1 increased in CGP-females, whereas Cyp19a1 increased in CGP-males. Serum FSH increased in CGP-males while prolactin increased in CGP-females. Testosterone and progesterone increased in ovaries from CGP-females, in which Kiss1, Cyp19a1 and Esr1 were downregulated while Hsd3b2 was upregulated, together with increased atretic and decreased ovulatory follicles. Testes from CGP-males showed decreased progesterone, increased Gabbr1, Kiss1, Kiss1r, Esr2 and decreased Cyp19a1 and clear signs of seminiferous tubules atrophy. Conclusion: These results demonstrate that appropriate GABAB signaling during this critical prepubertal period is necessary for the normal development of the HPG axis.

Effect of age on the 3,5,3′-tri-iodothyronine-induced increase in sugar uptake in rat thymocytes

1986 ◽  
Vol 110 (3) ◽  
pp. 511-515 ◽  
Author(s):  
J. Segal ◽  
B. R. Troen
Keyword(s):  
Female Rats ◽  
In Vivo Studies ◽  
Sugar Uptake ◽  
Male And Female Rats ◽  
Old Rats ◽  
Effect Of Age ◽  
Age And Sex ◽  
In Cells

ABSTRACT The effect of age on the responsiveness of rat thymocytes to 3,5,3′-tri-iodothyronine (T3) was studied. It has been demonstrated previously that the plasma membrane-mediated effect of T3 to increase sugar uptake by rat thymocytes is influenced by age and sex. In both sexes, T3 given in vitro stimulated sugar uptake in cells from animals of 15 days of age, had no effect at 21 days and was again effective at 26 days. In the male, thymocytes from animals of 40 days of age and older were refractory to T3. However, in the female, T3, although less effective than in cells from 26-day-old animals, remained stimulatory in cells from 40- and 60-day-old rats. T3 had no effect in cells from animals of 90 days of age and older. In in-vivo studies in which female rats of 26, 60 and 90 days of age were first injected with T3 and 1 h later with [3H]2-deoxyglucose, the responsiveness of thymocytes to T3 also declined progressively with advancing age; T3 was most effective in cells from 26-day-old animals, less stimulatory in 60-day-old and essentially without effect in cells from 90-day-old animals. From these observations we have concluded that in both male and female rats the responsiveness of thymocytes to T3 declines progressively with age, and that this decline occurs at an earlier age in cells obtained from males. J. Endocr. (1986) 110, 511–515

Increased hypothalamic somatostatin mRNA following dexamethasone administration in rats

1992 ◽  
Vol 127 (5) ◽  
pp. 416-419 ◽  
Author(s):  
Koji Nakagawa ◽  
Tatsuya Ishizuka ◽  
Chikara Shimizu ◽  
Yoshito Ito ◽  
Ichiji Wakabayashi
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Female Rats ◽  
Mrna Levels ◽  
Plasma Growth Hormone ◽  
Hormone Production ◽  
Blot Technique ◽  
Series Of Experiments

There is increasing evidence to suggest that supraphysiological doses of glucocorticoids suppress growth hormone secretion in vivo by augmenting somatostatin release from the hypothalamus; previously, we reported an increase in hypothalamic somatostatin content in dexamethasone-treated rats. To further examine whether the production of somatostatin really is augmented, hypothalamic somatostatin mRNA levels were determined by the Northern blot technique in female rats receiving 330 μg of dexamethasone daily for three days. In two series of experiments, hypothalamic somatostatin mRNA levels in dexamethasone-treated rats were significantly (p<0.05) increased to 133±19 (mean±sd)% and 153±38% of the controls. In the dexamethasone-treated rats, plasma growth hormone levels were markedly suppressed compared with those of the controls. These results further support the hypothesis that pharmacological doses of glucocorticoids increase the production and release of somatostatin from the hypothalamus and thus inhibit growth hormone secretion, overriding the direct stimulatory effect of glucocorticoids on growth hormone production at the pituitary level.

scholarly journals Xenoestrogens Ethinyl Estradiol and Zearalenone Cause Precocious Puberty in Female Rats via Central Kisspeptin Signaling

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 3996-4007 ◽  
Author(s):  
Rókus Kriszt ◽  
Zsuzsanna Winkler ◽  
Ágnes Polyák ◽  
Dániel Kuti ◽  
Csilla Molnár ◽  
...  
Keyword(s):  
Ethinyl Estradiol ◽  
Physiological Activity ◽  
Estrogen Receptor Α ◽  
Female Rats ◽  
Mrna Levels ◽  
Vaginal Opening ◽  
Fiber Density ◽  
Contraceptive Pills ◽  
Female Wistar Rats ◽  
Related Transcription Factor

Xenoestrogens from synthetic or natural origin represent an increasing risk of disrupted endocrine functions including the physiological activity of the hypothalamo-pituitary-gonad axis. Ethinyl estradiol (EE2) is a synthetic estrogen used in contraceptive pills, whereas zearalenone (ZEA) is a natural mycoestrogen found with increasing prevalence in various cereal crops. Both EE2 and ZEA are agonists of estrogen receptor-α and accelerate puberty. However, the neuroendocrine mechanisms that are responsible for this effect remain unknown. Immature female Wistar rats were treated with EE2 (10 μg/kg), ZEA (10 mg/kg), or vehicle for 10 days starting from postnatal day 18. As a marker of puberty, the vaginal opening was recorded and neuropeptide and related transcription factor mRNA levels were measured by quantitative real time PCR and in situ hybridization histochemistry. Both ZEA and EE2 accelerated the vaginal opening, increased the uterine weight and the number of antral follicles in the ovary, and resulted in the increased central expression of gnrh. These changes occurred in parallel with an earlier increase of kiss1 mRNA in the anteroventral and rostral periventricular hypothalamus and an increased kisspeptin (KP) fiber density and KP-GnRH appositions in the preoptic area. These changes are compatible with a mechanism in which xenoestrogens overstimulate the developmentally unprepared reproductive system, which results in an advanced vaginal opening and an enlargement of the uterus at the periphery. Within the hypothalamus, ZEA and EE2 directly activate anteroventral and periventricular KP neurons to stimulate GnRH mRNA. However, GnRH and gonadotropin release and ovulation are disrupted due to xenoestrogen-mediated inhibitory KP signaling in the arcuate nucleus.

PRECOCIOUS PUBERTY IN RATS WITH HYPOTHALAMIC LESIONS

1960 ◽  
Vol XXXIII (IV) ◽  
pp. 569-576 ◽  
Author(s):  
Ronald J. Gellert ◽  
William F. Ganong
Keyword(s):  
Precocious Puberty ◽  
Arcuate Nucleus ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Vaginal Opening ◽  
Mammillary Body ◽  
Immature Female ◽  
Hypothalamic Lesions ◽  
Electrolytic Lesions

ABSTRACT Eight female rats with electrolytic lesions involving the arcuate nucleus in the posterior tuberal region of the hypothalamus matured significantly earlier than unoperated controls. Lesions placed in the anterior hypothalamus, mammillary body, hippocampus, cortex and thalamus of immature female rats had no effect on the age at which vaginal opening and first oestrus occurred.

scholarly journals Alcohol Exposure during the Developmental Period Induces β-Endorphin Neuronal Death and Causes Alteration in the Opioid Control of Stress Axis Function

Endocrinology ◽  
2007 ◽  
Vol 148 (6) ◽  
pp. 2828-2834 ◽  
Author(s):  
Dipak K. Sarkar ◽  
Peter Kuhn ◽  
Jasson Marano ◽  
Cuiping Chen ◽  
Nadka Boyadjieva
Keyword(s):  
Neuronal Death ◽  
Arcuate Nucleus ◽  
Alcohol Exposure ◽  
Ethanol Exposure ◽  
Developmental Period ◽  
Stress Axis ◽  
Mrna Levels ◽  
Arcuate Nuclei ◽  
Tgf Β1

Proopiomelanocortin-producing neurons in the arcuate nucleus of the hypothalamus secrete β-endorphin (β-EP), which controls varieties of body functions including the feedback regulation of the CRH neuronal activity in the paraventricular nucleus of the hypothalamus. Whether ethanol exposure in developing rats induces β-EP neuronal death and alters their influence on CRH neurons in vivo has not been determined. We report here that binge-like ethanol exposures in newborn rats increased the number of apoptotic β-EP neurons in the arcuate nucleus of the hypothalamus. We also found that immediately after ethanol treatments there was a significant reduction in the expression of proopiomelanocortin and adenylyl cyclases mRNA and an increased expression of several TGF-β1-linked apoptotic genes in β-EP neurons isolated by laser-captured microdissection from arcuate nuclei of young rats. Several weeks after the ethanol treatment, we detected a reduction in the number of β-EP neuronal perikarya in arcuate nuclei and in the number of β-EP neuronal terminals in paraventricular nuclei of the hypothalamus in the treated rats. Additionally, these rats showed increased response of the hypothalamic CRH mRNA to the lipopolysaccharide challenge. The ethanol-treated animals also showed incompetent ability to respond to exogenous β-EP to alter the lipopolysaccharide-induced CRH mRNA levels. These data suggest that ethanol exposure during the developmental period causes β-EP neuronal death by cellular mechanisms involving the suppression of cyclic AMP production and activation of TGF-β1-linked apoptotic signaling and produces long-term structural and functional deficiency of β-EP neurons in the hypothalamus.

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