Paraventricular Dynorphin A Neurons Mediate LH Pulse Suppression Induced by Hindbrain Glucoprivation in Female Rats

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Hitomi Tsuchida ◽  
Parvin Mostari ◽  
Koki Yamada ◽  
Sae Miyazaki ◽  
Yuki Enomoto ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Critical Role ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Central Administration ◽  
Dynorphin A ◽  
Gonadotropin Secretion ◽  
Feedback Level ◽  
Estradiol 17Β

Abstract Malnutrition suppresses reproductive functions in mammals, which is considered to be mostly due to the inhibition of pulsatile gonadotropin-releasing hormone (GnRH)/gonadotropin secretion. Accumulating evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC) play a critical role in the regulation of pulsatile GnRH/gonadotropin release. The present study aimed to examine if the hypothalamic dynorphin A (Dyn) neurons mediate the suppression of GnRH/luteinizing hormone (LH) pulses during malnutrition. Ovariectomized rats treated with a negative feedback level of estradiol-17β-treated (OVX+E2) were administered with intravenous (iv) or fourth cerebroventricle (4V) 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, to serve as a malnutrition model. Central administration of a Dyn receptor antagonist blocked the iv- or 4V-2DG-induced suppression of LH pulses in OVX+E2 rats. The 4V 2DG administration significantly increased the number of Pdyn (Dyn gene)-positive cells co-expressing fos in the paraventricular nucleus (PVN), but not in the ARC and supraoptic nucleus (SON), and the iv 2DG treatment significantly increased the number of fos and Pdyn-co-expressing cells in the PVN and SON, but decreased it in the ARC. The E2 treatment significantly increased Pdyn expression in the PVN, but not in the ARC and SON. Double in situ hybridization for Kiss1 (kisspeptin gene) and Oprk1 (Dyn receptor gene) revealed that around 60% of ARC Kiss1-expressing cells co-expressed Oprk1. These results suggest that the PVN Dyn neurons, at least in part, mediate LH pulse suppression induced by the hindbrain or peripheral glucoprivation, and Dyn neurons may directly suppress the ARC kisspeptin neurons in female rats.

scholarly journals Overexpression of Corticotropin Releasing Factor in the Central Nucleus of the Amygdala Advances Puberty and Disrupts Reproductive Cycles in Female Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3934-3944 ◽  
Author(s):  
X. F. Li ◽  
M. H. Hu ◽  
S. Y. Li ◽  
C. Geach ◽  
A. Hikima ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Hpa Axis ◽  
Pulse Generator ◽  
Female Rats ◽  
Central Nucleus ◽  
Ovariectomized Rats ◽  
Human Society ◽  
Central Administration ◽  
Corticosterone Secretion ◽  
Stress Changes

Abstract Prolonged exposure to environmental stress activates the hypothalamic-pituitary-adrenal (HPA) axis and generally disrupts the hypothalamic-pituitary-gonadal axis. Because CRF expression in the central nucleus of the amygdala (CeA) is a key modulator in adaptation to chronic stress, and central administration of CRF inhibits the hypothalamic GnRH pulse generator, we tested the hypothesis that overexpression of CRF in the CeA of female rats alters anxiety behavior, dysregulates the HPA axis response to stress, changes pubertal timing, and disrupts reproduction. We used a lentiviral vector to increase CRF expression site specifically in the CeA of preweaning (postnatal day 12) female rats. Overexpression of CRF in the CeA increased anxiety-like behavior in peripubertal rats shown by a reduction in time spent in the open arms of the elevated plus maze and a decrease in social interaction. Paradoxically, puberty onset was advanced but followed by irregular estrous cyclicity and an absence of spontaneous preovulatory LH surges associated with proestrous vaginal cytology in rats overexpressing CRF. Despite the absence of change in basal corticosterone secretion or induced by stress (lipopolysaccharide or restraint), overexpression of CRF in the CeA significantly decreased lipopolysaccharide, but not restraint, stress-induced suppression of pulsatile LH secretion in postpubertal ovariectomized rats, indicating a differential stress responsivity of the GnRH pulse generator to immunological stress and a potential adaptation of the HPA axis to chronic activation of amygdaloid CRF. These data suggest that the expression profile of this key limbic brain CRF system might contribute to the complex neural mechanisms underlying the increasing incidence of early onset of puberty on the one hand and infertility on the other attributed to chronic stress in modern human society.

Effects of triiodothyronine, dexamethasone and estradiol-17β on GH mRNA in rat pituitary cells in culture as revealed by in situ hybridization

1991 ◽  
Vol 124 (1) ◽  
pp. 83-90 ◽  
Author(s):  
M. G. Martinoli ◽  
R. Veilleux ◽  
G. Pelletier
Keyword(s):  
In Situ Hybridization ◽  
Calf Serum ◽  
Female Rats ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Male And Female ◽  
Male And Female Rats ◽  
Rat Pituitary ◽  
Estradiol 17Β

Abstract. The GH lines of rat pituitary tumour cells have been largely used to study the regulation of GH mRNA. In order to investigate the role of T3, dexamethasone and estradiol-17β on GH expression in non-tumoural pituitary cells, we have used in situ hybridization techniques performed on rat anterior pituitary cells in monolayer culture. The amounts of mRNA encoding for GH, as evaluated by counting the number of grains per somatotrope, were markedly reduced after 4 days of culture in a steroid-free medium supplemented with an hypothyroid calf serum. Addition of T3 or dexamethasone for 3 days increased GH mRNA levels. The concomitant administration of the two hormones produced a synergistic effect on GH mRNA levels which became higher than those observed after T3 or dexamethasone administration alone. However, this effect did not restore GH mRNA levels to those measured in monolayer pituitary cells grown in medium containing 10% fetal calf serum. Moreover GH mRNA levels appeared higher in male than in female pituitary cells. The administration of E2 to pituitary cell cultures from both male and female rats produced an increase by 15, and 12.8% in GH mRNA levels in male and female, respectively. This stimulatory effect of E2 in cell culture was competitively blocked by simultaneous incubation with the antiestrogen LY156758 (Keoxifene). These results demonstrate that T3, dexamethasone as well as E2 act directly on somatotropic cells to regulate GH gene expression.

scholarly journals RFamide-Related Peptide-3 Receptor Gene Expression in GnRH and Kisspeptin Neurons and GnRH-Dependent Mechanism of Action

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3770-3779 ◽  
Author(s):  
Mohammed Z. Rizwan ◽  
Matthew C. Poling ◽  
Maggie Corr ◽  
Pamela A. Cornes ◽  
Rachael A. Augustine ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Receptor Gene ◽  
Male Rats ◽  
Gonadotropin Secretion ◽  
Female Mice ◽  
Related Peptide ◽  
Gnrh Neurons ◽  
Lh Secretion ◽  
G Protein Coupled

RFamide-related peptide-3 (RFRP-3) is known to inhibit the activity of GnRH neurons. It is not yet clear whether its G protein-coupled receptors, GPR147 and GPR74, are present on GnRH neurons or on afferent inputs of the GnRH neuronal network or whether RFRP-3 can inhibit gonadotropin secretion independently of GnRH. We tested the following: 1) whether GnRH is essential for the effects of RFRP-3 on LH secretion; 2) whether RFRP-3 neurons project to GnRH and rostral periventricular kisspeptin neurons in mice, and 3) whether Gpr147 and Gpr74 are expressed by these neurons. Intravenous treatment with the GPR147 antagonist RF9 increased plasma LH concentration in castrated male rats but was unable to do so in the presence of the GnRH antagonist cetrorelix. Dual-label immunohistochemistry revealed that approximately 26% of GnRH neurons from male and diestrous female mice were apposed by RFRP-3 fibers, and 19% of kisspeptin neurons from proestrous female mice were apposed by RFRP-3 fibers. Using immunomagnetic purification of GnRH and kisspeptin cells, single-cell nested RT-PCR, and in situ hybridization, we showed that 33% of GnRH neurons and 9–16% of rostral periventricular kisspeptin neurons expressed Gpr147, whereas Gpr74 was not expressed in either population. These data reveal that RFRP-3 can act at two levels of the GnRH neuronal network (i.e. the GnRH neurons and the rostral periventricular kisspeptin neurons) to modulate reproduction but is unable to inhibit gonadotropin secretion independently of GnRH.

scholarly journals Characterization of the Potent Gonadotropin-Releasing Activity of RF9, a Selective Antagonist of RF-Amide-Related Peptides and Neuropeptide FF Receptors: Physiological and Pharmacological Implications

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1902-1913 ◽  
Author(s):  
R. Pineda ◽  
D. Garcia-Galiano ◽  
M. A. Sanchez-Garrido ◽  
M. Romero ◽  
F. Ruiz-Pino ◽  
...  
Keyword(s):  
Female Rats ◽  
Central Administration ◽  
Gonadotropin Secretion ◽  
Male And Female ◽  
Selective Antagonist ◽  
Male And Female Rats ◽  
Neuropeptide Ff ◽  
Gonadotropin Inhibitory Hormone

Identification of RF-amide-related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone, has drawn considerable interest on its potential effects and mechanisms of action in the control of gonadotropin secretion in higher vertebrates. Yet, these analyses have so far relied mostly on indirect approaches, while direct assessment of their physiological roles has been hampered by the lack of suitable antagonists. RF9 was recently reported as a selective and potent antagonist of the receptors for RFRP (RFRPR) and the related neuropeptides, neuropeptide FF (NPFF) and neuropeptide AF (NPFF receptor). We show here that RF9 possesses very strong gonadotropin-releasing activities in vivo. Central administration of RF9 evoked a dose-dependent increase of LH and FSH levels in adult male and female rats. Similarly, male and female mice responded to intracerebroventricular injection of RF9 with robust LH secretory bursts. In rats, administration of RF9 further augmented the gonadotropin-releasing effects of kisspeptin, and its stimulatory effects were detected despite the prevailing suppression of gonadotropin secretion by testosterone or estradiol. In fact, blockade of estrogen receptor-α partially attenuated gonadotropin responses to RF9. Finally, systemic administration of RF9 modestly stimulated LH secretion in vivo, although no direct effects in terms of gonadotropin secretion were detected at the pituitary in vitro. Altogether, these data are the first to disclose the potent gonadotropin-releasing activity of RF9, a selective antagonist of RFRP (and NPFF) receptors. Our findings support a putative role of the RFRP/gonadotropin-inhibitory hormone system in the central control of gonadotropin secretion in mammals and have interesting implications concerning the potential therapeutic indications and pharmacological effects of RF9.

scholarly journals The 17α and 17β Isomers of Estradiol Both Induce Rapid Spine Synapse Formation in the CA1 Hippocampal Subfield of Ovariectomized Female Rats

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 287-293 ◽  
Author(s):  
Neil J. MacLusky ◽  
Victoria N. Luine ◽  
Tibor Hajszan ◽  
Csaba Leranth
Keyword(s):  
Spatial Memory ◽  
Synapse Formation ◽  
Hormone Replacement ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Maximal Response ◽  
Response Analysis ◽  
Potent Inducer ◽  
The Impact ◽  
Estradiol 17Β

Previous studies have demonstrated that estradiol-17β and estradiol-17α both induce short-latency effects on spatial memory in rats, estradiol-17α being at least as potent as its 17β isomer. To determine whether the mechanisms underlying these behavioral responses might include effects on hippocampal synaptic plasticity, CA1 pyramidal spine synapse density (PSSD) was measured in ovariectomized rats within the first few hours after sc estrogen injection. PSSD increased markedly (by 24%) 4.5 h after the administration of 45 μg/kg estradiol-17β. The PSSD response was significantly greater (44% above control) 30 min after estradiol-17β injection and was markedly dose dependent; a 3-fold lower estradiol-17β dose (15 μg/kg) did not significantly affect CA1 PSSD at either 30 min or 4.5 h. Estradiol-17α was a more potent inducer of PSSD than estradiol-17β. Dose-response analysis determined an ED50 for the effect of estradiol-17α on PSSD of 8.92 ± 1.99 μg/kg, with a maximal response at 15 μg/kg. These results demonstrate that high doses of estradiol induce rapid changes in CA1 PSSD. CA1 spine synapse formation appears to be more sensitive to estradiol-17α than to estradiol-17β, paralleling previous data on the effects of these two steroids on spatial memory. Rapid remodeling of hippocampal synaptic connections may thus contribute to the enhancement of spatial mnemonic processing observed within the first few hours after estrogen treatment. The potency of estradiol-17α suggests that hormone replacement therapy using this steroid might be useful clinically in ameliorating the impact of low endogenous estrogen production on the development and progression of neurodegenerative disorders involving the hippocampus.

Possible mechanisms of metabolic dysfunction in ovariectomized rats : impact of intrinsic aerobic fitness

2015 ◽  
Author(s):  
◽  
Young-Min Park
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Aerobic Capacity ◽  
Aerobic Fitness ◽  
Wheel Running ◽  
Critical Role ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Metabolic Dysfunction

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Ovariectomized (OVX) rodents are used as a model of human menopause as frequently both experience weight gain, decreased insulin sensitivity and decreased physical activity, which may manifest into metabolic syndrome. Intrinsic aerobic capacity may influence OVX-induced metabolic dysfunction. Female rats selectively bred for high (HCR) and low (LCR) aerobic capacity were used to elucidate the underlying mechanisms by which intrinsic aerobic fitness impacts OVX-associated metabolic dysfunction. We demonstrated that HCR were not fully protected against an OVX-induced decline in insulin sensitivity partially due to a [about]30% attenuation of insulin-stimulated skeletal muscle glucose uptake. HCROVX were protective against HFD-associated insulin resistance through a unique mechanism of behavioral change (i.e. compensatory increase in spontaneous physical activity), while LCROVX exacerbated insulin resistance following HFD. HCR were not protected from OVX-induced reduction in voluntary wheel running; yet HCRhad greater DA activation, compared to LCR, which was associated with their enhanced running distance. Collectively, these data suggest that high aerobic fitness may play a critical role in attenuating metabolic dysfunction associated with OVX and external stress due to their intrinsically enhanced insulin sensitivity. However, high aerobic fitness is not fully protective to OVX-induced impairments in metabolic function and physical activity levels, indicative of a strong physiological effect of ovarian hormone loss.

Interleukin-1β fever in rats: gender difference and estrous cycle influence

1998 ◽  
Vol 275 (5) ◽  
pp. R1450-R1454 ◽  
Author(s):  
A. Mouihate ◽  
X. Chen ◽  
Q. J. Pittman
Keyword(s):  
Estrous Cycle ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Febrile Response ◽  
Immune System Activation ◽  
System Activation ◽  
Fever Response ◽  
Estradiol 17Β ◽  
Hormonal Levels

Evidence exists to support the concept of sex difference in immune system activation by pyrogenic cytokines. In this study, fever development was monitored to analyze the effect of peripheral administration of interleukin (IL)-1β (1 μg/kg) in adult male and cycling or ovariectomized female rats with or without ovarian hormonal replacement. In male and randomly cycling female rats, a similar increase in body temperature occurred after intraperitoneal IL-1β injection. Two representative stages of estrus with higher and lower levels of ovarian hormones (proestrus and diestrus, respectively) were chosen for study of the febrile response induced by IL-1β. The fever induced by IL-1β was found to be significantly higher and more prolonged in females at proestrus than at diestrus. The differential fever response seems to be mainly linked to the ovarian hormonal levels because bilaterally ovariectomized females, supplemented with sequential injections of estradiol 17β and progesterone, showed a significantly higher IL-1β fever than did ovariectomized rats receiving estradiol 17β only. These results indicate that gonadal hormones can influence fever development and raise the possibility of interaction between sex hormones and thermogenesis in females during the estrous cycle.

Central μ-opioid receptor antagonism blocks glucoprivic LH pulse suppression and gluconeogenesis/feeding in female rats

Endocrinology ◽  
2021 ◽  
Author(s):  
Hitomi Tsuchida ◽  
Narumi Kawai ◽  
Koki Yamada ◽  
Marina Takizawa ◽  
Naoko Inoue ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Glucose Utilization ◽  
Marker Gene ◽  
Reproductive Function ◽  
Female Rats ◽  
Μ Opioid Receptor ◽  
Lh Release ◽  
Feedback Level ◽  
Gene Expressing ◽  
Estradiol 17Β

Abstract Energetic status often affects reproductive function, glucose homeostasis and feeding in mammals. Malnutrition suppresses pulsatile release of the gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) and increases gluconeogenesis and feeding. The present study aims to examine whether β-endorphin-μ-opioid receptor (MOR) signaling mediates the suppression of pulsatile GnRH/LH release, and an increase in gluconeogenesis/feeding induced by malnutrition. Ovariectomized female rats treated with a negative feedback level of estradiol-17β (OVX + low E2) receiving 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, intravenously (iv), were used as a malnutrition model. An administration of D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective MOR antagonist, into the 3 rd ventricle blocked the suppression of the LH pulse and increase in gluconeogenesis/feeding induced by iv 2DG administration. Histological analysis revealed that arcuate Kiss1 (kisspeptin gene)-expressing cells and preoptic Gnrh1 (GnRH gene)-expressing cells co-expressed little Oprm1, while around 10% of arcuate Slc17a6 (glutamatergic marker gene)-expressing cells co-expressed Oprm1. Further, the CTOP treatment decreased the number of fos-positive cells in the paraventricular nucleus (PVN) in OVX + low E2 rats treated with iv 2DG, but failed to affect the number of arcuate fos-expressing Slc17a6-positive cells. Taken together, these results suggest that the central β-endorphin-MOR signaling mediates the suppression of pulsatile LH release and that the β-endorphin may indirectly suppress the arcuate kisspeptin neurons, a master regulator for GnRH/LH pulses during malnutrition. Furthermore, the current study suggests that central β-endorphin-MOR signaling is also involved in gluconeogenesis and an increase in food intake by directly or indirectly acting on the PVN neurons during malnutrition in female rats.

Regulation by ovarian factors of the LHRH-induced LH response in pituitary glands in situ or grafted under the kidney capsule in intact and ovariectomized rats

1989 ◽  
Vol 123 (1) ◽  
pp. 41-45 ◽  
Author(s):  
J. A. M. J. van Dieten ◽  
J. de Koning ◽  
G. P. van Rees
Keyword(s):  
Pituitary Gland ◽  
High Rate ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Lag Phase ◽  
Kidney Capsule ◽  
Pituitary Glands ◽  
Lh Release ◽  
Secretory Products

ABSTRACT When pituitary glands from intact female rats are incubated with LHRH, the resulting LH release shows a biphasic pattern: an initial low rate of LH release (lag phase) is followed by a high rate. When pituitary glands from long-term ovariectomized rats are incubated, the rate of LH release is high throughout stimulation with LHRH. The disappearance of the lag phase might be due to increased LHRH release after ovariectomy and/or the disappearance of ovarian factors. To distinguish between these possibilities, pituitary glands which had been exposed to endogenous LHRH (pituitary glands in situ) or which had been unexposed to endogenous LHRH (pituitary glands transplanted under the kidney capsule) were incubated in the presence or absence of LHRH. Biphasic LH secretion patterns were observed during incubation with LHRH with the animal's own pituitary gland and with the transplanted pituitary gland from intact, but not from ovariectomized rats. Thus the disappearance of the lag phase after ovariectomy results from the absence of ovarian secretory products, rather than from increased release of LHRH. Journal of Endocrinology (1989) 123, 41–45

scholarly journals Osteoporosis Affects Functional Activity and Gene Expression of Osteoblastic Cells Derived from Rat Alveolar Bone

2020 ◽  
Vol 31 (6) ◽  
pp. 617-622
Author(s):  
Paula Katherine Vargas-Sanchez ◽  
Roger Rodrigo Fernandes ◽  
Flávia Aparecida Chaves Furlaneto ◽  
Luiz Gustavo de Sousa ◽  
Selma Siéssere ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Alveolar Bone ◽  
Bone Cells ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Osteoblastic Cells ◽  
Expression Of Genes ◽  
In Situ Detection

Abstract Recent studies suggest that osteoporosis, in addition to the damage caused in long bones, may cause deterioration in the jaws, especially in alveolar bone sites, with effects in the progress of periodontal disease as well as in bone healing. The aim of this study was to evaluate the effect of osteoporosis in the metabolism of rat alveolar bone osteoblasts. There were used 10 female rats divided in two experimental groups (Sham and OVX), which were ovariectomized and after 8 weeks euthanized to collect mandibular bone samples in order to isolate osteoblastic cells. The cells were cultured in 24-well plates to perform the in vitro experiments. After 7, 10 and 14 days, there were evaluated cell proliferation by MTT assay, in situ detection of alkaline phosphatase (ALP) as well as mineralized nodules and expression of genes associated to bone remodeling. Results showed that at 7, 10 and 14 days cell proliferation was lower for OVX group. In situ detection of ALP was higher at 7 days and lower at 10 and 14 days in OVX group. At 17 and 21 days, OVX group had a significative decrease of mineralization nodules. There was a downregulation in the expression of Alp, Bglap and Runx2 genes and an upregulation of Opg in OVX group, whereas Opn and Rankl modulation was similar between the evaluated groups. Our results suggest that osteoporosis has a deleterious effect on alveolar bone cells from ovariectomized rats, which might affect the treatment of diseases associated to the jaw bones.

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