Neuroendocrine integration of nutritional signals on reproduction

Evans, Maggie C.; Anderson, Greg M.

doi:10.1530/jme-16-0212

Cited by 55 publications

(39 citation statements)

References 239 publications

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“…GnRH neuronal processes, named “dendrons,” by Herbison group [3], form an interwoven network that receives direct synaptic and neuropeptide input from upstream regulatory neurons, most notably kisspeptin [4, 5]. This GnRH network integrates other signals that impinge on reproduction, such as stress [6, 7], endocrine disruptors [8], circadian rhythms [9, 10], metabolism [11, 12], and acute inflammation during infection [13-15]. …”

Section: Introductionmentioning

confidence: 99%

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Lainez

Coss²

2019

Neuroendocrinology

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Background: The mechanisms whereby neuroinflammation negatively affects neuronal function in the hypothalamus are not clear. Our previous study determined that obesity-mediated chronic inflammation elicits sex-specific impairment in reproductive function via reduction in spine density in gonadotropin-releasing hormone (GnRH) neurons. Neuroinflammation and subsequent decrease in GnRH neuron spine density was specific for male mice, while protection in females was independent of ovarian estrogens. Methods: To examine if neuroinflammation-induced cytokines can directly regulate GnRH gene expression, herein we examined signaling pathways and mechanisms in males in vivo and in GnRH-expressing cell line, GT1–7. Results: GnRH neurons express cytokine receptors, and chronic or acute neuroinflammation represses GnRH gene expression in vivo. Leukemia inhibitory factor (LIF) in particular represses GnRH expression in GT1–7 cells, while other cytokines do not. STAT3 and MAPK pathways are activated following LIF treatment, but only MAPK pathway, specifically p38α, is sufficient to repress the GnRH gene. LIF induces cFOS that represses the GnRH gene via the -1,793 site in the enhancer region. In vivo, following high-fat diet, cFOS is induced in GnRH neurons and neurons juxtaposed to the leaky blood brain barrier of the organum vasculosum of the lamina terminalis, but not in the neurons further away. Conclusion: Our results indicate that the increase in LIF due to neuroinflammation induces cFOS and represses the GnRH gene. Therefore, in addition to synaptic changes in GnRH neurons, neuroinflammatory cytokines directly regulate gene expression and reproductive function, and the specificity for neuronal targets may stem from the proximity to the fenestrated capillaries.

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Section: Introductionmentioning

confidence: 99%

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Lainez

Coss²

2019

Neuroendocrinology

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“…Other factors in addition to sex steroids could affect the inguinal fat pad as there is a clear link between adipocyte metabolism and reproduction [62, 63]. For example, reproduction is sensitive to leptin feedback as a signal of the nutritional status and level of fat accumulation in the body.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, all nutritional signals (e.g. adiponectin, insulin and ghrelin) with receptors on the GnRH neurons or their afferent neurons [63] would be ineffective due to the impaired GnRH receptor. However, these nutritional hormones also have peripheral effects.…”

Section: Discussionmentioning

confidence: 99%

Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

Busby

Sherwood

2017

PLoS ONE

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Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15–28 may account for the altered metabolism in the prepubertal female pups.

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“…However, it is worth mentioning the relatively recent discovery that the production of leptin, a peptide hormone produced by adipose tissues and also by the placenta, is now seen as an important modulator of diet, body condition and the neural control of reproduction (Barb et al, 2005;Daniel et al2013;Evans and Anderson, 2017). Extremes of body condition such as obesity or malnutrition are known to impact the success of reproduction in humans and other species (Hausman et al, 2012;Perez-Perez et al, 2015;Walzem and Chen, 2014).…”

Section: Reproduction In Eutherian Mammalsmentioning

confidence: 99%

Mammalian Reproduction Overview

Holt

Johnston

2018

Encyclopedia of Reproduction

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GlossaryAltricial Offspring that are hatched or born in a very immature and helpless condition so as to require parental care for some time. Delayed implantation Delayed implantation or embryonic diapause is a reproductive strategy used by approximately 100 different mammals in seven or eight different orders. In embryonic diapause, the embryo (blastocyst) does not immediately implant in the uterus after sexual reproduction has created the zygote, but is maintained in a state of dormancy. Eutheria Is the taxonomic name for the main group of living mammals. This taxon contains the placental mammals, of which humans are one species. Marsupials Mammals of an order whose members are born incompletely developed (i.e., altricial) and are typically carried and suckled in a pouch on the mother‫׳‬s belly. Marsupials are found chiefly in Australia and New Guinea, and also in America. Metatheria Is a mammalian clade that includes all mammals more closely related to marsupials than to placentals. It is a slightly more inclusive group than the marsupials; it contains all of the living mammals with abdominal pouches (most female marsupials) as well as their more primitive ancestors and relatives. Monotreme Any member of the Monotremata, the most primitive order of mammals, characterized by certain birdlike and reptilian features, such as hatching young from eggs, and having a single opening for the digestive, urinary, and genital organs. Platypus and echidnas are the only extent monotremes. Phylogeny The evolutionary history of a group of organisms, especially as depicted in a family tree. Prototherian Primitive oviparous mammals belonging to the order Monotremata.

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Neuroendocrine integration of nutritional signals on reproduction

Cited by 55 publications

References 239 publications

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

Mammalian Reproduction Overview

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