Victoria Lux-lantos - Academia.edu (original) (raw)

Papers by Victoria Lux-lantos

Research paper thumbnail of Further Evidence for the Inhibitory Action of Baclofen on a Prolactin-Releasing Factor

Experimental Biology and Medicine, 1991

The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chloroph... more The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chlorophenyl-gamma-aminobutyric acid or baclofen, in its inhibitory action on prolactin release, was studied. Dose-response studies of the effect of baclofen on prolactin (PRL) secretion were performed in stressed male rats. Furthermore, the action of the drug was evaluated in (i) rats treated with haloperidol or alpha-methyl-p-tyrosine, (ii) stressed or suckled rats pretreated with sulpiride, and (iii) animals treated with serotonin, alone, or with alpha-methyl-p-tyrosine. Baclofen showed a clear dose-dependent inhibition of prolactin secretion in males under stress. The drug was unable to inhibit the prolactin release induced by haloperidol or alpha-methyl-p-tyrosine, although it reduced the PRL secretion induced by serotonin. It also inhibited PRL release in sulpiride-pretreated stressed or suckled rats. These results suggest that the dose-dependent effect of baclofen on PRL secretion is the consequence of an inhibition exerted on the prolactin-releasing factor component of the neuroendocrine responses evoked by stress or suckling, possibly acting at the serotonergic system.

Research paper thumbnail of GABA< sub> B1</sub> Knockout Mice Reveal Alterations in Prolactin Levels, Gonadotropic Axis, and Reproductive Function

Neuroendocrinology, 2005

γ-Aminobutyric acid (GABA) has been implicated in the control of hypophyseal functions. We evalua... more γ-Aminobutyric acid (GABA) has been implicated in the control of hypophyseal functions. We evaluated whether the constitutive loss of functional GABA< sub> B</sub> receptors in GABA< sub> B1</sub> knockout (GABA< sub> B1</sub>< sup>–/–</sup>) mice alters hormonal levels, under basal and stimulated conditions, and reproductive function. The serum hormone levels were measured by radioimmunoassay, the estrous cyclicity was evaluated by vaginal lavages, and the mating behavior was determined by the presence ...

Research paper thumbnail of Effects of GABABAgonists and Antagonists on Glycemia Regulation in Mice

BASIC/TRANSLATIONAL - Obesity, Inflammation & Diabetes

Research paper thumbnail of Lack of Functional GABAB Receptors Disrupts Normal Kiss1 mRNA Expression in Neonatal Mice

BASIC/TRANSLATIONAL - Reproduction & Neuroendocrinology

Research paper thumbnail of GABAergic input through GABAB receptors is necessary during a perinatal window to shape gene expression of factors critical to reproduction such as Kiss1

American Journal of Physiology-Endocrinology and Metabolism

Lack of GABAB receptors in GABAB1 knockout mice decreases neonatal ARC kisspeptin 1 ( Kiss1) expr... more Lack of GABAB receptors in GABAB1 knockout mice decreases neonatal ARC kisspeptin 1 ( Kiss1) expression in the arcuate nucleus of the hypothalamus (ARC) in females, which show impaired reproduction as adults. Our aim was to selectively impair GABAB signaling during a short postnatal period to evaluate its impact on the reproductive system. Neonatal male and female mice were injected with the GABAB antagonist CGP 55845 (CGP, 1 mg/kg body wt sc) or saline from postnatal day 2 ( PND2) to PND6, three times per day (8 AM, 1 PM, and 6 PM). One group was killed on PND6 for collection of blood samples (hormones by radioimmunoassay), brains for gene expression in the anteroventral periventricular nucleus-periventricular nucleus continuum (AVPV/PeN), and ARC micropunches [quantitative PCR (qPCR)] and gonads for qPCR, hormone contents, and histology. A second group of mice was injected with CGP (1 mg/kg body wt sc) or saline from PND2 to PND6, three times per day (8 AM, 1 PM, and 6 PM), and le...

Research paper thumbnail of Mammary gland-specific regulation of GNRH and GNRH-receptor gene expression is likely part of a local autoregulatory system in female vizcachas (Rodentia: Chinchillidae)

General and Comparative Endocrinology

Research paper thumbnail of Calcium influx and intracellular stores in angiotensin II stimulation of normal and hyperplastic pituitary cells

American Journal of Physiology-Endocrinology and Metabolism

In rat pituitary cells from estrogen-induced hyperplasia, angiotensin II (ANG II) does not evoke ... more In rat pituitary cells from estrogen-induced hyperplasia, angiotensin II (ANG II) does not evoke a clear spike elevation of intracellular Ca2+concentration ([Ca2+]i) but induces a plateau increase. The present work was undertaken to establish whether this difference was related to a differential participation of intracellular and/or plasma membrane Ca2+ channels. We first tested the effect of 10 nM ANG II on [Ca2+]iin the absence of extracellular Ca2+ in cells depolarized with 25 mM K+ or in the presence of blockers of L-type voltage-sensitive Ca2+ channels (VSCC). These treatments did not alter spike elevation in [Ca2+]iin controls but reduced plateau levels in hyperplastic cells. Intracellular Ca2+ stores were similar in both groups, as assessed by thapsigargin treatment, but this drug abolished spike increase in controls and scarcely modified plateau levels in hyperplastic cells. Finally, inositol trisphosphate (InsP3) production in response to ANG II was significantly higher in ...

Research paper thumbnail of Early Exposure to a High-Fat Diet Impacts on Hippocampal Plasticity: Implication of Microglia-Derived Exosome-like Extracellular Vesicles

Molecular Neurobiology

Pág. 2 Alterations in endothelial and glial cells on the hippocampus of PDAPP mice, transgenic mo... more Pág. 2 Alterations in endothelial and glial cells on the hippocampus of PDAPP mice, transgenic model of Alzheimer's Disease. Interaction between components of the neurovascular unit.

Research paper thumbnail of Multiple failures in the LH surge generating system in GABAB 1 KO female mice

Journal of Neuroendocrinology

Research paper thumbnail of MON-031 In Vitro Exposure to Bisphenol A, Benzophenones 2 or 3, Have Different Effects on GnRH Gene Expression and Secretion in Mature and Immature GnRH Neurons

Journal of the Endocrine Society

Research paper thumbnail of SAT-409 A Novel Population of Kisspeptin Neurons in the Medial Tuberal Nucleus of the Hypothalamus in Mice

Journal of the Endocrine Society

Research paper thumbnail of SAT-165 Does Oligodeoxynucleotide IMT504 Have Any Effect On Beta Cells? A Preliminary Study On MIN6B1 Cell Line

Journal of the Endocrine Society

Research paper thumbnail of SAT-172 Continuous, Prolonged Treatment with the Oligonucleotide IMT504 in Diabetic NOD Mice Greatly Improves All Parameters of the Diabetic Condition

Journal of the Endocrine Society

Research paper thumbnail of Unraveling the connection between GABA and Kisspeptin in the control of reproduction

Reproduction

Neuroendocrine control of reproduction involves the interplay of various factors that become acti... more Neuroendocrine control of reproduction involves the interplay of various factors that become active at some point along development. GnRH is the main neurohormone controlling reproduction and among the most important inputs modulating GnRH synthesis/secretion are GABA and kisspeptins. These interactions of GABA and kisspeptin in the control of GnRH secretion can take place by the presence of the receptors of both factors on the GnRH neuron or alternatively by the actions of GABA on kisspeptin neurons and/or the actions of kisspeptin on GABA neurons. Kisspeptin acts on the Kiss1R, a seven transmembrane domain, Gαq/11–coupled receptor that activates phospholipase C, although some Gαq/11-independent pathways in mediating part of the effects of Kiss1R activation have also been proposed. GABA acts through two kinds of receptors, ionotropic GABAA/C receptors involving a chloride channel and associated with fast inhibitory/stimulatory conductance, and metabotropic GABAB receptors (GABABR) ...

Research paper thumbnail of Pituitary estrogen receptor alpha is involved in luteinizing hormone pulsatility at mid-gestation in the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

General and comparative endocrinology, Jan 12, 2018

The South American plains vizcacha, Lagostomus maximus, is a caviomorph rodent native from Argent... more The South American plains vizcacha, Lagostomus maximus, is a caviomorph rodent native from Argentina, Bolivia and Paraguay. It shows peculiar reproductive features like pre-ovulatory follicle recruitment during pregnancy with an ovulatory process at around mid-gestation. We have described the activation of the hypothalamic - pituitary - ovarian (HPO) axis during pregnancy. A progressive decrease of progesterone (P4) at mid-pregnancy elicits the delivery of gonadotropin-releasing hormone (GnRH) with the consequent secretion of follicle stimulating hormone (FSH) and estradiol (E) followed by luteinizing hormone (LH) release resulting in follicular luteinization and the P4 concentration recover. Pituitary gland is the central regulator of the HPO axis being E a key hormone involved in the regulation of its activity. In this work we analyzed the action of E on the pituitary response to the GnRH wave as well as its involvement on LH secretion at mid-gestation in L. maximus. The expressio...

Research paper thumbnail of {"__content__"=>"Local production of neurostradiol affects gonadotropin-releasing hormone (GnRH) secretion at mid-gestation in (Rodentia, Caviomorpha).", "i"=>{"__content__"=>"Lagostomus maximus"}}

Physiological reports, 2017

Females of the South American plains vizcacha, , show peculiar reproductive features such as mass... more Females of the South American plains vizcacha, , show peculiar reproductive features such as massive polyovulation up to 800 oocytes per estrous cycle and an ovulatory process around mid-gestation arising from the reactivation of the hypothalamic-hypophyseal-ovary (H.H.O.) axis. Estradiol (E) regulates gonadotropin-releasing hormone (GnRH) expression. Biosynthesis of estrogens results from the aromatization of androgens by aromatase, which mainly occurs in the gonads, but has also been described in the hypothalamus. The recently described correlation between GnRH and ER expression patterns in the hypothalamus of the vizcacha during pregnancy, with coexpression in the same neurons of the medial preoptic area, suggests that hypothalamic synthesis of E may affect GnRH neurons and contribute with systemic E to modulate GnRH delivery during the gestation. To elucidate this hypothesis, hypothalamic expression and the action of aromatase on GnRH release were evaluated in female vizcachas t...

Research paper thumbnail of Estradiol-Dependent and -Independent Stimulation of Kiss1 Expression in the Amygdala, BNST, and Lateral Septum of Mice

Endocrinology, 2018

Kisspeptin, encoded by Kiss1, activates reproduction by stimulating GnRH neurons. Although most K... more Kisspeptin, encoded by Kiss1, activates reproduction by stimulating GnRH neurons. Although most Kiss1 neurons are located in the hypothalamus, smaller Kiss1 populations also reside in the medial amygdala (MeA), bed nucleus of the stria terminalis (BnST), and lateral septum (LS). However, very little is known about the regulation and function of these extra-hypothalamic Kiss1 neurons. This study focused on the roles and interactions of two signaling factors, estradiol (E2) and GABA, known to stimulate and inhibit, respectively, extra-hypothalamic Kiss1 expression. First, using estrogen receptor (ER)α knockout (KO) and βERKO mice, we demonstrated that Kiss1 in both the BnST and LS is stimulated by E2, as occurs in the MeA, and that this E2 upregulation occurs via ERα, but not ERβ. Second, using GABABR KO and wild-type mice, we determined that whereas E2 normally increases extra-hypothalamic Kiss1 levels, such upregulation by E2 is further enhanced by the concurrent absence of GABABR s...

Research paper thumbnail of Neonatal exposure to bisphenol A alters the hypothalamic-pituitary-thyroid axis in female rats

Toxicology letters, Jan 15, 2018

Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in... more Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in many common products. Several reports revealed potent in vivo and in vitro effects. In this study we analyzed the effects of the exposure to BPA in the hypothalamic-pituitary-thyroid axis in female rats, both in vivo and in vitro. Female Sprague-Dawley rats were injected sc from postnatal day 1 (PND1) to PND10 with BPA: 500 μg 50 μloil (B500), or 50 μg 50 μl(B50), or 5 μg 50 μl(B5). Controls were injected with 50 μl vehicle during the same period. Neonatal exposure to BPA did not modify TSH levels in PND13 females, but it increased them in adults in estrus. Serum T4 was lower in B5 and B500 with regards to Control, whereas no difference was seen in T3. No significant differences were observed in TRH, TSHβ and TRH receptor expression between groups. TSH release from PPC obtained from adults in estrus was also higher in B50 with regard to Control. In vitro 24 h pre-treatment with BPA or E...

Research paper thumbnail of Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

World Journal of Stem Cells, 2017

Conflict-of-interest statement: López RA and Zorzopulos J are shareholders of Immunotech, the com... more Conflict-of-interest statement: López RA and Zorzopulos J are shareholders of Immunotech, the company that provided funding for several of the studies partially described in this review; Horn DL is the owner and CEO of David Horn, LLC, which owns all the IMT504 patents [Patents numbers: EP1511845B1. Immunostimulatory oligonucleotides and uses thereof. International application number: PCT/EP2003/005691. International publication number: WO2003/101375. US7943316(B2)]. There are no further patents, products in development, or marketed products to declare. These statements do not alter the authors' adherence to all the BPG policies on sharing data and material.

Research paper thumbnail of ERα and GnRH co-localize in the hypothalamic neurons of the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

Journal of Molecular Histology, 2017

Gonadotropin-releasing hormone (GnRH) is the key regulator of the hypothalamic-pituitary-gonadal ... more Gonadotropin-releasing hormone (GnRH) is the key regulator of the hypothalamic-pituitary-gonadal axis. Estradiol (E2) affects GnRH synthesis and delivery. Hypothalamic estrogen receptors (ER) modulate GnRH expression acting as transcription factors. The South American plains vizcacha, Lagostomus maximus, is able to ovulate up to 800 oocytes per reproductive cycle, and shows continuous folliculogenesis with pre-ovulatory follicle formation and an ovulatory event at mid-gestation. The aim of this work was to analyze the hypothalamic expression of ER in the vizcacha at different gestational time-points, and its relationship with GnRH expression, serum luteinizing hormone (LH) and E2. The hormonal pattern of mid-gestating vizcachas was comparable to ovulating-females with significant increases in GnRH, LH and E2. Hypothalamic protein and mRNA expression of ERα varied during pregnancy with a significant increase at mid-gestation whereas ERβ mRNA expression did not show significant variations. Hypothalamic immunolocalization of ERα was observed in neurons of the diagonal band of Brocca, medial preoptic area (mPOA), periventricular, suprachiasmatic, supraoptic (SON), ventromedial, and arcuate nuclei, and medial eminence, with a similar distribution throughout gestation. In addition, all GnRH neurons of the mPOA and SON showed ERα expression with no differences across the reproductive status. The correlation between GnRH and ERα at mid-gestation, and their co-localization in the hypothalamic neurons of the vizcacha, provides novel information compared with other mammals suggesting a direct action of estrogen as part of a differential reproductive strategy to assure GnRH synthesis during pregnancy.

Research paper thumbnail of Further Evidence for the Inhibitory Action of Baclofen on a Prolactin-Releasing Factor

Experimental Biology and Medicine, 1991

The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chloroph... more The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chlorophenyl-gamma-aminobutyric acid or baclofen, in its inhibitory action on prolactin release, was studied. Dose-response studies of the effect of baclofen on prolactin (PRL) secretion were performed in stressed male rats. Furthermore, the action of the drug was evaluated in (i) rats treated with haloperidol or alpha-methyl-p-tyrosine, (ii) stressed or suckled rats pretreated with sulpiride, and (iii) animals treated with serotonin, alone, or with alpha-methyl-p-tyrosine. Baclofen showed a clear dose-dependent inhibition of prolactin secretion in males under stress. The drug was unable to inhibit the prolactin release induced by haloperidol or alpha-methyl-p-tyrosine, although it reduced the PRL secretion induced by serotonin. It also inhibited PRL release in sulpiride-pretreated stressed or suckled rats. These results suggest that the dose-dependent effect of baclofen on PRL secretion is the consequence of an inhibition exerted on the prolactin-releasing factor component of the neuroendocrine responses evoked by stress or suckling, possibly acting at the serotonergic system.

Research paper thumbnail of GABA< sub> B1</sub> Knockout Mice Reveal Alterations in Prolactin Levels, Gonadotropic Axis, and Reproductive Function

Neuroendocrinology, 2005

γ-Aminobutyric acid (GABA) has been implicated in the control of hypophyseal functions. We evalua... more γ-Aminobutyric acid (GABA) has been implicated in the control of hypophyseal functions. We evaluated whether the constitutive loss of functional GABA< sub> B</sub> receptors in GABA< sub> B1</sub> knockout (GABA< sub> B1</sub>< sup>–/–</sup>) mice alters hormonal levels, under basal and stimulated conditions, and reproductive function. The serum hormone levels were measured by radioimmunoassay, the estrous cyclicity was evaluated by vaginal lavages, and the mating behavior was determined by the presence ...

Research paper thumbnail of Effects of GABABAgonists and Antagonists on Glycemia Regulation in Mice

BASIC/TRANSLATIONAL - Obesity, Inflammation & Diabetes

Research paper thumbnail of Lack of Functional GABAB Receptors Disrupts Normal Kiss1 mRNA Expression in Neonatal Mice

BASIC/TRANSLATIONAL - Reproduction & Neuroendocrinology

Research paper thumbnail of GABAergic input through GABAB receptors is necessary during a perinatal window to shape gene expression of factors critical to reproduction such as Kiss1

American Journal of Physiology-Endocrinology and Metabolism

Lack of GABAB receptors in GABAB1 knockout mice decreases neonatal ARC kisspeptin 1 ( Kiss1) expr... more Lack of GABAB receptors in GABAB1 knockout mice decreases neonatal ARC kisspeptin 1 ( Kiss1) expression in the arcuate nucleus of the hypothalamus (ARC) in females, which show impaired reproduction as adults. Our aim was to selectively impair GABAB signaling during a short postnatal period to evaluate its impact on the reproductive system. Neonatal male and female mice were injected with the GABAB antagonist CGP 55845 (CGP, 1 mg/kg body wt sc) or saline from postnatal day 2 ( PND2) to PND6, three times per day (8 AM, 1 PM, and 6 PM). One group was killed on PND6 for collection of blood samples (hormones by radioimmunoassay), brains for gene expression in the anteroventral periventricular nucleus-periventricular nucleus continuum (AVPV/PeN), and ARC micropunches [quantitative PCR (qPCR)] and gonads for qPCR, hormone contents, and histology. A second group of mice was injected with CGP (1 mg/kg body wt sc) or saline from PND2 to PND6, three times per day (8 AM, 1 PM, and 6 PM), and le...

Research paper thumbnail of Mammary gland-specific regulation of GNRH and GNRH-receptor gene expression is likely part of a local autoregulatory system in female vizcachas (Rodentia: Chinchillidae)

General and Comparative Endocrinology

Research paper thumbnail of Calcium influx and intracellular stores in angiotensin II stimulation of normal and hyperplastic pituitary cells

American Journal of Physiology-Endocrinology and Metabolism

In rat pituitary cells from estrogen-induced hyperplasia, angiotensin II (ANG II) does not evoke ... more In rat pituitary cells from estrogen-induced hyperplasia, angiotensin II (ANG II) does not evoke a clear spike elevation of intracellular Ca2+concentration ([Ca2+]i) but induces a plateau increase. The present work was undertaken to establish whether this difference was related to a differential participation of intracellular and/or plasma membrane Ca2+ channels. We first tested the effect of 10 nM ANG II on [Ca2+]iin the absence of extracellular Ca2+ in cells depolarized with 25 mM K+ or in the presence of blockers of L-type voltage-sensitive Ca2+ channels (VSCC). These treatments did not alter spike elevation in [Ca2+]iin controls but reduced plateau levels in hyperplastic cells. Intracellular Ca2+ stores were similar in both groups, as assessed by thapsigargin treatment, but this drug abolished spike increase in controls and scarcely modified plateau levels in hyperplastic cells. Finally, inositol trisphosphate (InsP3) production in response to ANG II was significantly higher in ...

Research paper thumbnail of Early Exposure to a High-Fat Diet Impacts on Hippocampal Plasticity: Implication of Microglia-Derived Exosome-like Extracellular Vesicles

Molecular Neurobiology

Pág. 2 Alterations in endothelial and glial cells on the hippocampus of PDAPP mice, transgenic mo... more Pág. 2 Alterations in endothelial and glial cells on the hippocampus of PDAPP mice, transgenic model of Alzheimer's Disease. Interaction between components of the neurovascular unit.

Research paper thumbnail of Multiple failures in the LH surge generating system in GABAB 1 KO female mice

Journal of Neuroendocrinology

Research paper thumbnail of MON-031 In Vitro Exposure to Bisphenol A, Benzophenones 2 or 3, Have Different Effects on GnRH Gene Expression and Secretion in Mature and Immature GnRH Neurons

Journal of the Endocrine Society

Research paper thumbnail of SAT-409 A Novel Population of Kisspeptin Neurons in the Medial Tuberal Nucleus of the Hypothalamus in Mice

Journal of the Endocrine Society

Research paper thumbnail of SAT-165 Does Oligodeoxynucleotide IMT504 Have Any Effect On Beta Cells? A Preliminary Study On MIN6B1 Cell Line

Journal of the Endocrine Society

Research paper thumbnail of SAT-172 Continuous, Prolonged Treatment with the Oligonucleotide IMT504 in Diabetic NOD Mice Greatly Improves All Parameters of the Diabetic Condition

Journal of the Endocrine Society

Research paper thumbnail of Unraveling the connection between GABA and Kisspeptin in the control of reproduction

Reproduction

Neuroendocrine control of reproduction involves the interplay of various factors that become acti... more Neuroendocrine control of reproduction involves the interplay of various factors that become active at some point along development. GnRH is the main neurohormone controlling reproduction and among the most important inputs modulating GnRH synthesis/secretion are GABA and kisspeptins. These interactions of GABA and kisspeptin in the control of GnRH secretion can take place by the presence of the receptors of both factors on the GnRH neuron or alternatively by the actions of GABA on kisspeptin neurons and/or the actions of kisspeptin on GABA neurons. Kisspeptin acts on the Kiss1R, a seven transmembrane domain, Gαq/11–coupled receptor that activates phospholipase C, although some Gαq/11-independent pathways in mediating part of the effects of Kiss1R activation have also been proposed. GABA acts through two kinds of receptors, ionotropic GABAA/C receptors involving a chloride channel and associated with fast inhibitory/stimulatory conductance, and metabotropic GABAB receptors (GABABR) ...

Research paper thumbnail of Pituitary estrogen receptor alpha is involved in luteinizing hormone pulsatility at mid-gestation in the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

General and comparative endocrinology, Jan 12, 2018

The South American plains vizcacha, Lagostomus maximus, is a caviomorph rodent native from Argent... more The South American plains vizcacha, Lagostomus maximus, is a caviomorph rodent native from Argentina, Bolivia and Paraguay. It shows peculiar reproductive features like pre-ovulatory follicle recruitment during pregnancy with an ovulatory process at around mid-gestation. We have described the activation of the hypothalamic - pituitary - ovarian (HPO) axis during pregnancy. A progressive decrease of progesterone (P4) at mid-pregnancy elicits the delivery of gonadotropin-releasing hormone (GnRH) with the consequent secretion of follicle stimulating hormone (FSH) and estradiol (E) followed by luteinizing hormone (LH) release resulting in follicular luteinization and the P4 concentration recover. Pituitary gland is the central regulator of the HPO axis being E a key hormone involved in the regulation of its activity. In this work we analyzed the action of E on the pituitary response to the GnRH wave as well as its involvement on LH secretion at mid-gestation in L. maximus. The expressio...

Research paper thumbnail of {"__content__"=>"Local production of neurostradiol affects gonadotropin-releasing hormone (GnRH) secretion at mid-gestation in (Rodentia, Caviomorpha).", "i"=>{"__content__"=>"Lagostomus maximus"}}

Physiological reports, 2017

Females of the South American plains vizcacha, , show peculiar reproductive features such as mass... more Females of the South American plains vizcacha, , show peculiar reproductive features such as massive polyovulation up to 800 oocytes per estrous cycle and an ovulatory process around mid-gestation arising from the reactivation of the hypothalamic-hypophyseal-ovary (H.H.O.) axis. Estradiol (E) regulates gonadotropin-releasing hormone (GnRH) expression. Biosynthesis of estrogens results from the aromatization of androgens by aromatase, which mainly occurs in the gonads, but has also been described in the hypothalamus. The recently described correlation between GnRH and ER expression patterns in the hypothalamus of the vizcacha during pregnancy, with coexpression in the same neurons of the medial preoptic area, suggests that hypothalamic synthesis of E may affect GnRH neurons and contribute with systemic E to modulate GnRH delivery during the gestation. To elucidate this hypothesis, hypothalamic expression and the action of aromatase on GnRH release were evaluated in female vizcachas t...

Research paper thumbnail of Estradiol-Dependent and -Independent Stimulation of Kiss1 Expression in the Amygdala, BNST, and Lateral Septum of Mice

Endocrinology, 2018

Kisspeptin, encoded by Kiss1, activates reproduction by stimulating GnRH neurons. Although most K... more Kisspeptin, encoded by Kiss1, activates reproduction by stimulating GnRH neurons. Although most Kiss1 neurons are located in the hypothalamus, smaller Kiss1 populations also reside in the medial amygdala (MeA), bed nucleus of the stria terminalis (BnST), and lateral septum (LS). However, very little is known about the regulation and function of these extra-hypothalamic Kiss1 neurons. This study focused on the roles and interactions of two signaling factors, estradiol (E2) and GABA, known to stimulate and inhibit, respectively, extra-hypothalamic Kiss1 expression. First, using estrogen receptor (ER)α knockout (KO) and βERKO mice, we demonstrated that Kiss1 in both the BnST and LS is stimulated by E2, as occurs in the MeA, and that this E2 upregulation occurs via ERα, but not ERβ. Second, using GABABR KO and wild-type mice, we determined that whereas E2 normally increases extra-hypothalamic Kiss1 levels, such upregulation by E2 is further enhanced by the concurrent absence of GABABR s...

Research paper thumbnail of Neonatal exposure to bisphenol A alters the hypothalamic-pituitary-thyroid axis in female rats

Toxicology letters, Jan 15, 2018

Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in... more Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in many common products. Several reports revealed potent in vivo and in vitro effects. In this study we analyzed the effects of the exposure to BPA in the hypothalamic-pituitary-thyroid axis in female rats, both in vivo and in vitro. Female Sprague-Dawley rats were injected sc from postnatal day 1 (PND1) to PND10 with BPA: 500 μg 50 μloil (B500), or 50 μg 50 μl(B50), or 5 μg 50 μl(B5). Controls were injected with 50 μl vehicle during the same period. Neonatal exposure to BPA did not modify TSH levels in PND13 females, but it increased them in adults in estrus. Serum T4 was lower in B5 and B500 with regards to Control, whereas no difference was seen in T3. No significant differences were observed in TRH, TSHβ and TRH receptor expression between groups. TSH release from PPC obtained from adults in estrus was also higher in B50 with regard to Control. In vitro 24 h pre-treatment with BPA or E...

Research paper thumbnail of Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

World Journal of Stem Cells, 2017

Conflict-of-interest statement: López RA and Zorzopulos J are shareholders of Immunotech, the com... more Conflict-of-interest statement: López RA and Zorzopulos J are shareholders of Immunotech, the company that provided funding for several of the studies partially described in this review; Horn DL is the owner and CEO of David Horn, LLC, which owns all the IMT504 patents [Patents numbers: EP1511845B1. Immunostimulatory oligonucleotides and uses thereof. International application number: PCT/EP2003/005691. International publication number: WO2003/101375. US7943316(B2)]. There are no further patents, products in development, or marketed products to declare. These statements do not alter the authors' adherence to all the BPG policies on sharing data and material.

Research paper thumbnail of ERα and GnRH co-localize in the hypothalamic neurons of the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)

Journal of Molecular Histology, 2017

Gonadotropin-releasing hormone (GnRH) is the key regulator of the hypothalamic-pituitary-gonadal ... more Gonadotropin-releasing hormone (GnRH) is the key regulator of the hypothalamic-pituitary-gonadal axis. Estradiol (E2) affects GnRH synthesis and delivery. Hypothalamic estrogen receptors (ER) modulate GnRH expression acting as transcription factors. The South American plains vizcacha, Lagostomus maximus, is able to ovulate up to 800 oocytes per reproductive cycle, and shows continuous folliculogenesis with pre-ovulatory follicle formation and an ovulatory event at mid-gestation. The aim of this work was to analyze the hypothalamic expression of ER in the vizcacha at different gestational time-points, and its relationship with GnRH expression, serum luteinizing hormone (LH) and E2. The hormonal pattern of mid-gestating vizcachas was comparable to ovulating-females with significant increases in GnRH, LH and E2. Hypothalamic protein and mRNA expression of ERα varied during pregnancy with a significant increase at mid-gestation whereas ERβ mRNA expression did not show significant variations. Hypothalamic immunolocalization of ERα was observed in neurons of the diagonal band of Brocca, medial preoptic area (mPOA), periventricular, suprachiasmatic, supraoptic (SON), ventromedial, and arcuate nuclei, and medial eminence, with a similar distribution throughout gestation. In addition, all GnRH neurons of the mPOA and SON showed ERα expression with no differences across the reproductive status. The correlation between GnRH and ERα at mid-gestation, and their co-localization in the hypothalamic neurons of the vizcacha, provides novel information compared with other mammals suggesting a direct action of estrogen as part of a differential reproductive strategy to assure GnRH synthesis during pregnancy.