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The Influence of Circulating Sex Hormones on Severe Intermittent Hypoxia‐Induced Phrenic Long‐Term Facilitation in Female and Male Rats
Author(s) -
Dougherty Brendan
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02885
Subject(s) - hormone , estrogen , biology , estrous cycle , endocrinology , medicine
Multiple, stimulus‐specific cellular mechanisms give rise to phrenic long‐term facilitation (pLTF), a well‐studied form of respiratory neuroplasticity. We recently demonstrated that circulating sex hormones are critical for induction of pLTF following moderate acute intermittent hypoxia (mAIH; 35‐45mmHG Pa O 2 ) in adult female rats; mAIH‐induced pLTF is not expressed during estrous cycle stages with low circulating 17β‐estradiol (the most neuroactive form of estrogen) or following removal of the ovaries, the primary source of circulating sex hormones. Castrated male rats also do not express mAIH‐induced pLTF supporting a link between circulating sex hormones and pLTF expression in males as well. More severe AIH protocols (sAIH; 25‐35mmHg Pa O 2 ) induce pLTF through a unique set of cellular pathways. However, all studies of sAIH‐induced pLTF to date have been completed in young‐adult, gonadally‐intact male rats. Our primary Aims for these studies were two‐fold: 1) determine if sAIH‐induced pLTF was expressed in female rats across stages of the estrous cycle; and 2) determine if removal of the gonads (ovaries or testicles) influenced expression of sAIH‐induced pLTF. We hypothesized that sAIH‐induced pLTF would be expressed in females regardless of estrous cycle stage, and that sAIH‐induced pLTF would be expressed in both females and males following removal of the gonads. Young adult (12‐13 weeks) female and male Sprague‐Dawely rats were used for each study. In study 1, pLTF was quantified in female rats on the morning of estrus (low circulating 17β‐estradiol) or proestrus (high circulating 17β‐estradiol) based on examination of vaginal cell characteristics in vaginal smears using light microscopy. In study 2, ovariectomy or castration was completed at least 7 days prior to pLTF assessments. Contrary to our hypothesis, preliminary results suggest that sAIH‐induced pLTF may be significantly influenced by circulating sex hormones. Though female rats exhibited sAIH‐induced plasticity across estrous cycle stages, the magnitude of pLTF was associated with circulating estradiol levels. Additionally, removal of the gonads abolished the expression of sAIH‐induced pLTF in both female and male rats, suggesting a direct influence of sex hormones on sAIH mechanisms to pLTF. These data provide further evidence that sex hormones may play a critical role in expression of AIH‐induced respiratory neuroplasticity.