Prostaglandin synthesis mediates the suppression of arcuate Kiss1 neuron activation and pulsatile luteinizing hormone secretion during immune/inflammatory stress in female mice
Year: 2025
Type: article
Abstract: Stress induces a series of compensatory mechanisms with the objective of restoration or adaptation of physiological function. A common casualty of the response to stress is impaired reproduction via the inhibition of pulsatile luteinizing hormone (LH) secretion; however, how stressors convey LH inhibition remains unclear and may be dependent on stress type. Immune/inflammatory stress, modeled with peripheral lipopolysaccharide (LPS) exposure, induces a systemic inflammatory response which may contrast with the neural mechanisms employed by psychosocial stressors. We examined the suppressive effect of LPS versus psychosocial stress, modeled with restraint, on pulsatile LH secretion and investigated the neural mechanisms underlying LPS-induced LH suppression in ovariectomized (OVX) female mice. We observed that both LPS and restraint significantly suppressed mean LH concentrations; however, the dynamics of pulse suppression displayed stress-type dependency. LPS induced a reduction in both LH pulse frequency and amplitude, whereas restraint suppressed LH pulse frequency without compromising pulse amplitude. Next, we investigated the mediatory role of immune/inflammatory signaling for LPS to impair LH secretion and upstream arcuate Kiss1 cell function. Peripheral administration of flurbiprofen, a prostaglandin synthesis inhibitor, blocked the suppressive effect of LPS on LH pulse frequency and amplitude. Interestingly, flurbiprofen only partially prevented the suppressive effect of LPS on arcuate Kiss1 cell activity, as measured by c-Fos expression. These data demonstrate that immune/inflammatory stress inhibits the activity of the LH pulse generator, in part, via a prostaglandin-dependent pathway and supports the role of differential neural mechanisms mediating LH pulse suppression during stress.
Source: Journal of Neuroendocrinology
DOI: 10.1111/jne.70004
Institution: University of California San Diego
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Regulation of gonadotropin secretion during undernutrition by a brainstem-hypothalamic neural pathway, Investigation of brainstem neurons in the regulation of gonadotropin secretion, G3752029025, G6209994949, G66353979, G6691228967, G725142646, Investigation of Anatomical and Functional Mechanisms Underlying the Suppression of Gonadotropin Secretion by Metabolic Stress, Training in Reproductive Sciences
OpenAlex ID: W4408301704