Peripheral interleukin-1β inhibits arcuate kiss1 cells and LH pulses in female mice

Peripheral immune/inflammatory challenges rapidly disrupt reproductive neuroendocrine function. This inhibition is considered to be centrally mediated via suppression of gonadotropin-releasing hormone secretion, yet the neural pathway(s) for this effect remains unclear. We tested the hypothesis that...

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Bibliographic Details
Published in:	Journal of endocrinology Vol. 246; no. 2; pp. 149 - 160
Main Authors:	Makowski, Katherine N, Kreisman, Michael J, McCosh, Richard B, Raad, Ali A, Breen, Kellie M
Format:	Journal Article
Language:	English
Published:	England Bioscientifica Ltd 01-08-2020
Subjects:	Animals Estradiol - metabolism Female Gonadotropin-Releasing Hormone - genetics Gonadotropin-Releasing Hormone - metabolism Inflammation - genetics Inflammation - metabolism Interleukin-1beta - genetics Interleukin-1beta - metabolism Kisspeptins - genetics Kisspeptins - metabolism Luteinizing Hormone - metabolism Mice Ovariectomy Proto-Oncogene Proteins c-fos - genetics Proto-Oncogene Proteins c-fos - metabolism Receptors, Interleukin-1 - genetics Receptors, Interleukin-1 - metabolism stress luteinizing hormone GnRH immune/inflammatory
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Summary:	Peripheral immune/inflammatory challenges rapidly disrupt reproductive neuroendocrine function. This inhibition is considered to be centrally mediated via suppression of gonadotropin-releasing hormone secretion, yet the neural pathway(s) for this effect remains unclear. We tested the hypothesis that interleukin-1β inhibits pulsatile luteinizing hormone secretion in female mice via inhibition of arcuate kisspeptin cell activation, a population of neurons considered to be the gonadotropin-releasing hormone pulse generator. In the first experiment, we determined that the inhibitory effect of peripheral interleukin-1β on luteinizing hormone secretion was enhanced by estradiol. We next utilized serial sampling and showed that interleukin-1β reduced the frequency of luteinizing hormone pulses in ovariectomized female mice treated with estradiol. The interleukin-1β-induced suppression of pulse frequency was associated with reduced kisspeptin cell activation, as determined by c-Fos coexpression, but not as a result of impaired responsiveness to kisspeptin challenge. Together, these data suggest an inhibitory action of interleukin-1β upstream of kisspeptin receptor activation. We next tested the hypothesis that estradiol enhances the activation of brainstem nuclei responding to interleukin-1β. We determined that the expression of interleukin-1 receptor was elevated within the brainstem following estradiol. Interleukin-1β induced c-Fos in the area postrema, ventrolateral medulla, and nucleus of the solitary tract; however, the response was not increased by estradiol. Collectively, these data support a neural mechanism whereby peripheral immune/inflammatory stress impairs reproductive neuroendocrine function via inhibition of kisspeptin cell activation and reduced pulsatile luteinizing hormone secretion. Furthermore, these findings implicate the influence of estradiol on peripherally mediated neural pathways such as those activated by peripheral cytokines.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 K.N.M. and M.J.K. analyzed the data K.N.M., M.J.K., R.B.M., A.A.R. and K.M.B. edited and approved the manuscript. Co-first authors contributed equally Author contribution statement (optional) K.N.M., M.J.K., R.B.M. and K.M.B. designed the research study K.N.M., M.J.K., R.B.M., A.A.R. performed the research K.N.M. and K.M.B. wrote the paper, and
ISSN:	0022-0795 1479-6805
DOI:	10.1530/JOE-20-0165