A Novel Tissue-Specific Insight into Sex Steroid Fluctuations Throughout the Murine Estrous Cycle

Abstract Serum sex steroid levels fluctuate throughout the reproductive cycle. However, the degree to which sex steroid tissue content mimics circulating content is unknown. Understanding the flux and physiological quantity of tissue steroid content is imperative for targeted hormonal therapy develo...

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Veröffentlicht in:Endocrinology (Philadelphia) 2024-01, Vol.165 (1), p.1
Hauptverfasser: Unger, Christian A, Hope, Marion C, Aladhami, Ahmed K, Cotham, William E, Socia, Cassidy E, Rice, Barton C, Clegg, Deborah J, Velázquez, Kandy T, LaVoie, Holly A, Hollis, Fiona, Enos, Reilly T
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container_issue 1
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container_title Endocrinology (Philadelphia)
container_volume 165
creator Unger, Christian A
Hope, Marion C
Aladhami, Ahmed K
Cotham, William E
Socia, Cassidy E
Rice, Barton C
Clegg, Deborah J
Velázquez, Kandy T
LaVoie, Holly A
Hollis, Fiona
Enos, Reilly T
description Abstract Serum sex steroid levels fluctuate throughout the reproductive cycle. However, the degree to which sex steroid tissue content mimics circulating content is unknown. Understanding the flux and physiological quantity of tissue steroid content is imperative for targeted hormonal therapy development. Utilizing a gold-standard ultrasensitive liquid chromatography–mass spectrometry (LC/MS) method we determined sex steroid (17β-estradiol [E2], testosterone, androstenedione, and progesterone) fluctuations in serum and in 15 tissues throughout the murine estrous cycle (proestrus, estrus, and diestrus I) and in ovariectomized (OVX) mice. We observed dynamic fluctuations in serum and tissue steroid content throughout the estrous cycle with proestrus generally presenting the highest content of E2, testosterone, and androstenedione, and lowest content of progesterone. In general, the trend in circulating steroid content between the stages of the estrous cycle was mimicked in tissue. However, the absolute amounts of steroid levels when normalized to tissue weight were found to be significantly different between the tissues with the serum steroid quantity often being significantly lower than the tissue quantity. Additionally, we found that OVX mice generally displayed a depletion of all steroids in the various tissues assessed, except in the adrenal glands which were determined to be the main site of peripheral E2 production after ovary removal. This investigation provides a comprehensive analysis of steroid content throughout the estrous cycle in a multitude of tissues and serum. We believe this information will help serve as the basis for the development of physiologically relevant, tissue-specific hormonal therapies.
doi_str_mv 10.1210/endocr/bqad175
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However, the degree to which sex steroid tissue content mimics circulating content is unknown. Understanding the flux and physiological quantity of tissue steroid content is imperative for targeted hormonal therapy development. Utilizing a gold-standard ultrasensitive liquid chromatography–mass spectrometry (LC/MS) method we determined sex steroid (17β-estradiol [E2], testosterone, androstenedione, and progesterone) fluctuations in serum and in 15 tissues throughout the murine estrous cycle (proestrus, estrus, and diestrus I) and in ovariectomized (OVX) mice. We observed dynamic fluctuations in serum and tissue steroid content throughout the estrous cycle with proestrus generally presenting the highest content of E2, testosterone, and androstenedione, and lowest content of progesterone. In general, the trend in circulating steroid content between the stages of the estrous cycle was mimicked in tissue. However, the absolute amounts of steroid levels when normalized to tissue weight were found to be significantly different between the tissues with the serum steroid quantity often being significantly lower than the tissue quantity. Additionally, we found that OVX mice generally displayed a depletion of all steroids in the various tissues assessed, except in the adrenal glands which were determined to be the main site of peripheral E2 production after ovary removal. This investigation provides a comprehensive analysis of steroid content throughout the estrous cycle in a multitude of tissues and serum. We believe this information will help serve as the basis for the development of physiologically relevant, tissue-specific hormonal therapies.</description><identifier>ISSN: 1945-7170</identifier><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/endocr/bqad175</identifier><identifier>PMID: 37967240</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>17β-Estradiol ; Adrenal glands ; Androstenedione ; Animals ; Endocrine therapy ; Estradiol ; Estrous Cycle - physiology ; Estrus cycle ; Female ; Fluctuations ; Gonadal Steroid Hormones ; Liquid chromatography ; Mass spectrometry ; Mass spectroscopy ; Medical equipment and supplies industry ; Medical test kit industry ; Mice ; Ovariectomy ; Physiological aspects ; Progesterone ; Reproductive cycle ; Sex hormones ; Steroid hormones ; Steroids ; Testosterone ; Tissues</subject><ispartof>Endocrinology (Philadelphia), 2024-01, Vol.165 (1), p.1</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2024 Oxford University Press</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c435t-1ecd10903a242800f471325e6706e49a4d6cdd0d9931983ad51b5729f610d91b3</cites><orcidid>0000-0001-5571-4586</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37967240$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Unger, Christian A</creatorcontrib><creatorcontrib>Hope, Marion C</creatorcontrib><creatorcontrib>Aladhami, Ahmed K</creatorcontrib><creatorcontrib>Cotham, William E</creatorcontrib><creatorcontrib>Socia, Cassidy E</creatorcontrib><creatorcontrib>Rice, Barton C</creatorcontrib><creatorcontrib>Clegg, Deborah J</creatorcontrib><creatorcontrib>Velázquez, Kandy T</creatorcontrib><creatorcontrib>LaVoie, Holly A</creatorcontrib><creatorcontrib>Hollis, Fiona</creatorcontrib><creatorcontrib>Enos, Reilly T</creatorcontrib><title>A Novel Tissue-Specific Insight into Sex Steroid Fluctuations Throughout the Murine Estrous Cycle</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Abstract Serum sex steroid levels fluctuate throughout the reproductive cycle. However, the degree to which sex steroid tissue content mimics circulating content is unknown. Understanding the flux and physiological quantity of tissue steroid content is imperative for targeted hormonal therapy development. Utilizing a gold-standard ultrasensitive liquid chromatography–mass spectrometry (LC/MS) method we determined sex steroid (17β-estradiol [E2], testosterone, androstenedione, and progesterone) fluctuations in serum and in 15 tissues throughout the murine estrous cycle (proestrus, estrus, and diestrus I) and in ovariectomized (OVX) mice. We observed dynamic fluctuations in serum and tissue steroid content throughout the estrous cycle with proestrus generally presenting the highest content of E2, testosterone, and androstenedione, and lowest content of progesterone. In general, the trend in circulating steroid content between the stages of the estrous cycle was mimicked in tissue. However, the absolute amounts of steroid levels when normalized to tissue weight were found to be significantly different between the tissues with the serum steroid quantity often being significantly lower than the tissue quantity. Additionally, we found that OVX mice generally displayed a depletion of all steroids in the various tissues assessed, except in the adrenal glands which were determined to be the main site of peripheral E2 production after ovary removal. This investigation provides a comprehensive analysis of steroid content throughout the estrous cycle in a multitude of tissues and serum. 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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects 17β-Estradiol
Adrenal glands
Androstenedione
Animals
Endocrine therapy
Estradiol
Estrous Cycle - physiology
Estrus cycle
Female
Fluctuations
Gonadal Steroid Hormones
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Medical equipment and supplies industry
Medical test kit industry
Mice
Ovariectomy
Physiological aspects
Progesterone
Reproductive cycle
Sex hormones
Steroid hormones
Steroids
Testosterone
Tissues
title A Novel Tissue-Specific Insight into Sex Steroid Fluctuations Throughout the Murine Estrous Cycle
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