cFos Activity Identifies Recruitment of Luteinizing Hormone‐Releasing Hormone Neurons During the Ascending Phase of the Proestrous Luteinizing Hormone Surge

Lee, Wen-See; Smith, M. Susan; Hoffman, Gloria E.

doi:10.1111/j.1365-2826.1992.tb00154.x

Cited by 68 publications

(40 citation statements)

References 54 publications

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“…As an immediate early gene, cFOS is induced via activity-dependent transcription in neurons. cFOS expression is increased in activated GnRH neurons, during the preovulatory LH surge and after kisspeptin treatment [124, 125]. We, on the other hand, posit that location of the cFOS induction is dependent on the proximity to the vasculature.…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

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

Lainez

Coss²

2019

Neuroendocrinology

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“…Studies in which increasing numbers of LHRH neu rons express nuclear Fos immunoreactivity during the LH surge in rats [22,23] and mice [24] suggest that recruit ment of LHRH neurons may be important to the induc tion of the preovulatory LH surge. Furthermore, blockade of progesterone's action by the administration of RU486 reduced the proestrous LH surge and the number of LHRH neurons expressing Fos [25], Most reports in which the presence of gonadal steroid hormone receptors in LHRH neurons has been investi gated have concluded that few, if any, LHRH neurons con tain gonadal steroid receptors. This conclusion has been reached in studies of estrogen receptors, progestin receptors and androgen receptors and is based upon work in a variety of species, including rats [2,3,26,27], guinea pigs [4], sheep [28,29], and chickens [30], There are a variety of explana- tions for the positive findings reported here.…”

Section: Discussionmentioning

confidence: 99%

A Subgroup of LHRH Neurons in Guinea Pigs with Progestin Receptors Is Centrally Positioned within the Total Population of LHRH Neurons

et al. 1995

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Although the role of gonadal steroids in inducing the LH surge is undisputed, the mechanism(s) whereby steroids induce the release of the hypothalamic luteinizing hormone-releasing hormone (LHRH) remain(s) enigmatic. In this study we examined the issue of the presence of steroid receptors in LHRH neurons using a mammalian species that has a true luteal phase, namely, guinea pigs. Progestin receptors (PR) were localized in LHRH neurons of ovariectomized guinea pigs administered estradiol (10–20 µg estradiol benzoate) for 3-4 days, using several different immunocytochemical protocols. The subgroup of LHRH neurons containing PR, although small, was strategically positioned within the core of the total population of LHRH neurons. This central position was visualized in simultaneous views of three-dimensional computer reconstructions of the populations of LHRH/PR neurons and LHRH neurons. The subgroup of LHRH/PR neurons formed a thread permeating the population of LHRH neurons. We propose that in guinea pigs, LHRH neurons containing progestin receptors, are foci of activity, capable of activating a larger component of the LHRH population of cells in certain endocrine conditions, such as prior to the LH surge.

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“…Lee and coworkers have observed that the immediate-early the concepts that the galanin gene expression in GnRH neurons is dependent on the induction of c-fos and that like the immediate genes c-fos and c-jun are induced in GnRH neurons during the proestrous LH surge (20)(21)(22). The presence of these markers of early genes, galanin mRNA induction is associated with GnRH neuronal activation.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Steroid‐Induced Galanin mRNA Expression in GnRH Neurons by Specific NMDA‐Receptor Blockade

Rossmanith

Marks

Steiner

et al. 1996

J Neuroendocrinology

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Galanin mRNA levels in GnRH neurons increase in association with a steroid-induced LH surge in female rats. Both the steroid-induced LH surge and the concomitant increase of galanin mRNA in GnRH neurons are blocked by non-specific inhibition of central nervous system activity imposed by pentobarbital and specific central alpha-adrenergic receptor blockade. Based on these observations, we hypothesized that galanin gene expression in GnRH neurons is induced whenever GnRH neurons become activated to generate an LH surge. If this were the case, then any neurotransmitter receptor blocking agent that inhibits the LH surge by central mechanisms would likewise block the associated increase in galanin mRNA in GnRH neurons. We tested this hypothesis by examining the effects of an N-methyl-D-aspartate (NMDA) receptor antagonist on the steroid-induced LH surge and on levels of galanin mRNA in GnRH neurons. Three groups of ovariectomized rats were used: Group 1-treated with estradiol and progesterone (E/P) and sacrificed at the peak of the LH surge; Group 2-treated the same as Group 1 except that dizocilpine (MK801, an NMDA receptor antagonist) was used to block the LH surge; and Group 3-treated the same as Group 1 except they received vehicle instead of E/P. Double-and single-label in situ hybridization followed by computerized image analysis were used to measure levels of galanin mRNA and GnRH mRNA in GnRH neurons [as grains/cell (g/c)]. E/P treatment induced a 3-fold increase in LH levels and a 5-fold increase in the galanin mRNA signal content of GnRH neurons. Treatment with MK801 completely prevented the LH surge in all animals and also blocked the steroid-induced increase in galanin mRNA in GnRH neurons. As assessed by 2 independent GnRH single-labeled assays, neither GnRH message content nor the number of identifiable GnRH neurons differed among the experimental groups. We conclude that the increase in galanin mRNA levels in GnRH neurons is tightly coupled to the occurrence of a steroid-evoked LH surge, and we infer that induction of galanin gene expression in GnRH neurons is induced as a consequence of synaptic activation of GnRH neurons.Rising plasma levels of ovarian steroids in the female rat lead to either a general anesthetic (pentobarbital ) or a specific a-adrenergic blocking agent (phenoxybenzamine) prevents the induction an activation of gonadotropin-releasing hormone (GnRH ) neurons whose amplified secretory activity results in the preovulatory of galanin gene expression in GnRH neurons, even in the presence high levels of ovarian steroids ( 9). Based on these observations, release of LH ( 1). Several neurotransmitters are thought to be involved in the process of generating an LH surge, including we hypothesized that galanin mRNA induction in GnRH neurons is tightly coupled to the occurrence of an LH surge; therefore, neuropeptide Y, norepinephrine, and galanin (2 ). Galanin is expressed in a variety of neurons throughout the brain, including any agent that blocks the LH surge should also prevent th...

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cFos Activity Identifies Recruitment of Luteinizing Hormone‐Releasing Hormone Neurons During the Ascending Phase of the Proestrous Luteinizing Hormone Surge

Cited by 68 publications

References 54 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

A Subgroup of LHRH Neurons in Guinea Pigs with Progestin Receptors Is Centrally Positioned within the Total Population of LHRH Neurons

Inhibition of Steroid‐Induced Galanin mRNA Expression in GnRH Neurons by Specific NMDA‐Receptor Blockade

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