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Department of Obstetrics, Gynecology & Reproductive Sciences OB/GYN
  1. Department of OBGYN & Reproductive Sciences
  2. Research
  3. Faculty Labs
  4. Breen Church Lab
  5. Publications

Publications

Complete List of Publications

 

Featured Publications

Neural Control of Reproduction in Response to Stress

Stress is well-known to inhibit reproductive function, but the mechanisms by which various stressors alter reproductive neuroendocrine output remain incompletely defined. My research program has focused extensively on understanding the neural control of the reproductive cycle in the female, using both large and small animal models to probe the neuroanatomical and functional role of neuroendocrine sites and cellular mechanisms underlying the effect of stress on LH pulses and generation of the LH surge. The Breen Church lab is investigating the anatomical and functional pathways activated by different stress types [(i.e. psychosocial (2017), metabolic (2019), immune (2020)]. Our recent review (McCosh, et all 2019) highlights our understanding of signaling molecules and neural substrates activated by stress.

  1. Yang JA, Song CI, Hughes JK, Kreisman MJ, Parra RA, Haisenleder DJ, Kauffman AS, Breen KM. Acute psychosocial stress Inhibits LH pulsatility and Kiss1 neuronal activation in female mice. Endocrinology, 158: 3716–3723, 2017. PMC5695836
  2. McCosh RB, Kreisman MJ, Tian K, Ho BS, Thackray VG, Breen KM. Insulin-induced hypoglycaemia suppresses pulsatile luteinising hormone secretion and arcuate Kiss1 cell activation in female mice. J Neuroendocrinol. 31:e12813. 2019. PMC6933080
  3. Makowski, KN, Kriesman, MJ, McCosh, RB, Raad, AA, Breen, KM. Peripheral interleukin-1β inhibits arcuate Kiss1 cells and LH pulses in female mice. Journal of Endocrinology. Online ahead of print. 2020. PMID32464599
  4. McCosh RB, Kauffman AS*, Breen KM*. (*, co-last authors contributed equally). Neural and endocrine mechanisms underlying stress-induced suppression of pulsatile LH secretion. Mol Cell Endocrinol 498:110579. 2019. PMC6874223

Role of Glucocorticoids as a Stress Mediator

When this work began the “upstream” neural circuits in the brain that conveys activation of LH pulses or during the LH surge were poorly understood; the influence of stress and elevated glucocorticoids was an even greater mystery. We used the ewe to chronical the inhibitory effect of elevated CORT on the follicular phase, first in 2000, while a Master’s student at UC Davis, and then followed up at Michigan in 2005. These studies showed us that CORT impairs multiple aspects of follicular phase events, including generation of the LH surge. We next identified that neural processing of the preovulatory estradiol signal was impaired by CORT (2009), but the cell type in which CORT was acting remained elusive. My independent research group has expanded upon this line of study using the mouse to genetically probe kisspeptin neurons in the ARC and AVPV and neuropeptide players involved in disruption of LH pulses (2019) and the LH surge (2016).

  1. Kreisman MJ, McCosh RB, Tian K, Song C, Breen KM. Estradiol enables chronic corticosterone to inhibit pulsatile LH secretion and suppress Kiss1 neuronal activation in female mice. Neuroendocrinology 110:501-516, 2019. PMID31461711
  2. Luo E, Stephens SB, Chaing S, Munaganuru N, Kauffman AS, Breen KM. Corticosterone blocks estrous cyclicity and the LH surge via decreased kisspeptin neuron activation in female mice. Endocrinology, 157:1187-1199, 2016. PMC4769373

Influence of Estradiol on Stress Responses

One of the goals of my research program is to understand the common and unique pathways whereby different types of stressors alter hypothalamic control of physiologic function. The female is exquisitely sensitive to alterations in ovarian steroid milieu, principally mediated by circulating levels of estradiol. We have utilized the mouse in powerful ways to probe the role of estradiol on stress-activated neurocircuitry. In 2019 we published the development of an estradiol-replacement paradigm and used this paradigm that CORT impairs LH pulsatility via suppression of KNDy cells. We just recently published our work showing that estradiol enhances the inhibitory effect of an immune cytokine (2020). Collectively, this work has begun to tease apart the physiologic regulation of estradiol-influenced stress pathways on hypothalamic neuroendocrine function.

  1. Kreisman MJ, McCosh RB, Tian K, Song C, Breen KM. Estradiol enables chronic corticosterone to inhibit pulsatile LH secretion and suppress Kiss1 neuronal activation in female mice. Neuroendocrinology 110:501-516, 2019. PMID31461711
  2. Makowski, KN, Kriesman, MJ, McCosh, RB, Raad, AA, Breen, KM. Peripheral interleukin-1β inhibits arcuate Kiss1 cells and LH pulses in female mice. Journal of Endocrinology. Online ahead of print. 2020. PMID32464599