Insulin-induced hypoglycemia suppresses pulsatile LH secretion and arcuate Kiss1 cell activation in female mice

Stress suppresses pulsatile LH secretion in a variety of species, however the mechanism underlying this inhibition of reproductive function remains unclear. Metabolic stress, particularly hypoglycemia, is a clinically-relevant stress type that is modeled with bolus insulin injection (insulin-induced...

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Veröffentlicht in:Journal of neuroendocrinology 2019-12, Vol.31 (12), p.e12813-e12813
Hauptverfasser: McCosh, Richard B., Kreisman, Michael J., Tian, Katherine, Ho, Bryan S., Thackray, Varykina G., Breen, Kellie M.
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Sprache:eng
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Zusammenfassung:Stress suppresses pulsatile LH secretion in a variety of species, however the mechanism underlying this inhibition of reproductive function remains unclear. Metabolic stress, particularly hypoglycemia, is a clinically-relevant stress type that is modeled with bolus insulin injection (insulin-induced hypoglycemia). The present study utilized ovariectomized C57BL/6 mice to test the hypothesis that acute hypoglycemia suppresses pulsatile LH secretion via central mechanisms. Pulsatile LH secretion was measured in 90-min sampling periods immediately prior to and following an intraperitoneal (i.p.) injection of saline or insulin. The secretion of LH was not altered over time in fed animals or acute fasted (5 h) animals following an i.p. saline injection. In contrast, insulin elicited a robust suppression of pulsatile LH secretion in fasted animals, preventing LH pulses in 5 of 6 mice. To identify the neuroendocrine site of impairment, a kisspeptin challenge was performed in saline or insulin pre-treated animals in a cross-over design. LH secretion in response to exogenous kisspeptin was not different between animals pre-treated with saline or insulin, indicating normal GnRH cell and pituitary responses during acute hypoglycemia. Based on this finding, the effect of insulin-induced hypoglycemia on arcuate kisspeptin (Kiss1) cell function was determined using c-Fos as a marker of neuronal activation. Insulin caused a significant suppression in the percentage of Kiss1 cells in the arcuate nucleus that contained c-Fos, compared to saline-injected controls. Together these data support the hypothesis that insulin-induced hypoglycemia suppresses pulsatile LH secretion in the female mouse via predominantly central mechanisms, which culminates in suppression of the arcuate Kiss1 population.
ISSN:0953-8194
1365-2826
DOI:10.1111/jne.12813