Intracrinology
Abstract
A large proportion of androgens in men (40%), and the majority of estrogens in women (75% before menopause and close to 100% after menopause), are synthesized in peripheral target tissues from precursor steroids of adrenal origin. The genes encoding the enzymes responsible for the formation and metabolism of androgens and estrogens are expressed in a large series of peripheral tissues, thus providing the basis for a promising new area in hormone action, namely intracrinology. These steroidogenic and steroid metabolizing enzymes should become a major target of novel therapies for steroid-sensitive diseases, particularly breast and prostate cancer.
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Peripheral cell specific activation and inactivation is known as pre- and post-receptor steroid metabolism or steroid intracrinology.
“This process of peripheral cell specific activation and inactivation is known as pre- and post-receptor steroid metabolism or steroid ” intracrinology” [45,[59], [60], [61]].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [59]
Metabolism of activated androgens prevents over-activation of the AR and the release of significant amounts of activated androgens back into circulation.
“This metabolism prevents the over-activation of the AR as well as the release of significant amounts of the activated androgens back into circulation (Labrie, 1991).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Labrie, 1991
Locally produced sex steroids exert their action in the same cells in which their synthesis takes place without significant diffusion into the circulation.
“where the locally produced sex steroids are exerting their action in the same cells in which their synthesis takes place without significant diffusion into the circulation”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
Most of the androgens in women, especially after menopause, are synthesized in peripheral intracrine tissues from the inactive precursors DHEA and DHEA-S of adrenal origin.
“most of the androgens in women, especially after menopause, are synthesized in peripheral intracrine tissues from the inactive precursors dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) of adrenal origin.”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
Sex steroids made in peripheral tissues are inactivated locally into more water-soluble compounds that diffuse into the general circulation where they can be measured.
“The sex steroids made in peripheral tissues are then inactivated locally into more water-soluble compounds that diffuse into the general circulation where they can be measured.”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
Supplementation with physiological amounts of exogenous DHEA permits the biosynthesis of androgens and estrogens only in target tissues that contain the specific steroidogenic enzymes.
“supplementation with physiological amounts of exogenous DHEA permits the biosynthesis of androgens (essentially testosterone and DHT) and estrogens only in the target tissues that contain the specific steroidogenic enzymes (25,33).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
The best estimate of the intracrine formation of estrogens in peripheral tissues in women is in the order of 75% before menopause and close to 100% after menopause.
“Our best estimate of the intracrine formation of estrogens in peripheral tissues in women is in the order of 75% before menopause and close to 100% after menopause (25).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
Because the postmenopausal ovary does not secrete estrogens, intratumoral E2 is necessarily made from adrenal precursor steroids.
“Because the postmenopausal ovary does not secrete estrogens, intratumoral E 2 is necessarily made from adrenal precursor steroids (25).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
Man is unique, with some other primates, in having adrenals that secrete large amounts of the precursor steroids DHEA and DHEA-S, which are converted into 4-dione and then into potent androgens and/or estrogens in peripheral tissues.
“Man is unique, with some other primates, in having adrenals that secrete large amounts of the precursor steroids DHEA and DHEA-S, which are converted into 4-dione and then into potent androgens and/or estrogens in peripheral tissues (Refs.25, 77, and 78; Fig. 3).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
Human adrenals secrete large amounts of precursor steroids DHEA and DHEA-S, both converted into androgens in target intracrine tissues.
“the human adrenals secrete large amounts of the precursor steroids DHEA and DHEA-S, both of which are converted into androgens in target intracrine tissues (25,35,78,92,249,254,255).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
Inhibition of tumor growth seen after DHEA treatment in ovariectomized animals results from its intracrine in situ conversion into androgens in the mammary gland.
“the inhibition of tumor growth seen after DHEA treatment in ovariectomized animals results from its intracrine in situ conversion into androgens in the mammary gland (25,35,78,92,255).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
By itself, DHEA does not possess significant androgenic or estrogenic activity; its activity depends on transformation into androgens and/or estrogens in peripheral target intracrine tissues.
“by itself, DHEA does not possess any significant androgenic or estrogenic activity, its activity being dependent upon its transformation into androgens and/or estrogens in peripheral target intracrine tissues (25).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
Women at menopause are not only deprived from estrogens because of rapid loss of ovarian activity but also have been deprived from androgens for a longer period because of progressive decrease of serum DHEA levels starting years before menopause.
“women, at menopause, are not only deprived from estrogens because of a rapid loss of ovarian activity but also have been deprived from androgens for a longer period because of a progressive decrease of serum DHEA levels starting quite a few years before menopause.”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [25]
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Androgen biosynthetic pathways in the human prostate
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Self-citationGonadotropin-Releasing Hormone Agonists in the Treatment of Prostate Cancer
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RetractedStructural and functional biology of aldo-keto reductase steroid transforming enzymes
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Estrogen Biosynthesis and Action in Ovarian Cancer
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Profiling transcript levels for steroidogenic enzymes in fetal tissues
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Androgen metabolism in adipose tissue: Recent advances
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The Intracrine Sex Steroid Biosynthesis Pathways
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Self-citationContribution of age and declining androgen levels to features of the metabolic syndrome in men
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Complexities of androgen receptor signalling in breast cancer
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Characterization and regulation of UDP-glucuronosyltransferases in steroid target tissues
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Steroid biosynthesis in adipose tissue
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Estrogen and SERM neuroprotection in animal models of Parkinson's disease
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Aromatase inhibitors: past, present and future
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Characterization, Expression, and Immunohistochemical Localization of 5α-Reductase in Human Skin
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Self-citationSexual Dysfunction after Premenopausal Stage I and II Breast Cancer: Do Androgens Play a Role?
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Molecular therapy of breast cancer: progress and future directions
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Steroid biosynthesis and prostate cancer
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- Authors
- Labrie, F.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Corresponding author
- Labrie, Fernand
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 1991-07
- Volume
- 78
- Issue
- 3
- Pages
- C113-C118
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W4246234200
- Cited by
- 685
- References
- 29
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 6 · 2023: 15 · 2022: 17 · 2021: 17 · 2020: 8 · 2019: 18 · 2018: 20 · 2017: 19 · 2016: 21 · 2015: 27 · 2014: 30 · 2013: 22 · 2012: 17
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Keywords
- intracrinology, androgen production, estrogen synthesis, steroidogenic enzymes, steroid metabolism, tissue-specific gene expression, breast cancer, prostate cancer
- MeSH terms
- Adrenal Glands, Androgens, Breast Neoplasms, Dehydroepiandrosterone, Estrogens, Female, Humans, Male, Menopause, Prostatic Neoplasms, Gene Expression, Dehydroepiandrosterone Sulfate
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