Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate.

LABRIE, CLAUDE; SIMARD, JACQUES; ZHAO, HUI FEN; BELANGER, ALAIN; PELLETIER, GEORGES; LABRIE, FERNAND

doi:10.1210/endo-124-6-2745

Cited by 80Prostate Cancer Treatment and ResearchHormonal and reproductive studiesEstrogen and related hormone effects

Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate.

LABRIE, CLAUDE, SIMARD, JACQUES, ZHAO, HUI FEN, BELANGER, ALAIN, PELLETIER, GEORGES, LABRIE, FERNAND·1989·Endocrinology

DOI 10.1210/endo-124-6-2745

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Abstract

Androgens play a major role in the development, growth, and function of accessory sexual organs, especially the prostate. However, the testis is not the sole source of circulating androgens in man, since the adrenal gland secretes dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione (delta 4-dione) in large quantities. The aim of the present study was to investigate the effect of plasma concentrations of DHEA and delta 4-dione similar to those found in adult man on sensitive and specific markers of androgen action in the rat ventral prostate. In addition to ventral prostate weight, we have measured the steady state levels of the mRNAs encoding the C1 component of rat prostatic binding protein (PBP-C1) and spermine-binding protein (SBP) using 35S-labeled cDNA probes for in situ hybridization. One week after castration, ventral prostate weight fell 84%, while prostatic 5 alpha-dihydrotestosterone (DHT) and androgen-dependent mRNAs were undetectable. When administered via Silastic implants to castrated adult rats for 1 week, plasma concentrations of 1.37 +/- 0.06 ng/ml DHEA or 0.43 +/- 0.08 ng/ml delta 4-dione independently caused increases in ventral prostate weight to 33% and 65% of normal values, respectively. The same plasma levels of DHEA and delta 4-dione resulted in high intraprostatic levels of DHT to 1.19 +/- 0.34 and 3.66 +/- 0.89 ng/g tissue, respectively. Furthermore, DHEA caused an increase in the steady state levels of PBP-C1 and SBP mRNAs to 50% and 57% of the normal state, respectively, while delta 4-dione caused increases corresponding to 80% and 119% of control values, respectively. Castrated adult rats receiving testosterone at a concentration of 1.66 +/- 0.37 ng/ml plasma maintained normal ventral prostate weight and gene expression levels. The present results demonstrate that circulating levels of the adrenal steroids DHEA and delta 4-dione comparable to those found in man cause an important stimulation of androgen-dependent gene expression in the rat, probably after their conversion to DHT in the prostatic tissue itself.

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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 [249]
DHEA possesses relatively potent androgenic activity and stimulates androgen-dependent gene expression in the rat ventral prostate.
“Labrie and colleagues (78, 249) first demonstrated that DHEA possesses relatively potent androgenic activity and stimulates androgen-dependent gene expression in the rat ventral prostate.”
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 [249]
DHEA is converted into androgens, and treatment with DHEA induces androgen-sensitive gene expression in the rat ventral prostate.
“DHEA is well known to be converted into androgens, and treatment with DHEA is known to induce androgen-sensitive gene expression in the rat ventral prostate (78, 249).”
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 [249]

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Androgenic activity of dehydroepiandrosterone and androstenedione in the rat ventral prostate.
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Abstract 3746: Targeting adrenal androgen to treat prostate cancer
Wu, Y. H., Wang, J., Tang, L., POP, E. A., Stocking, J. J., Attwood, K. M., & Smith, G. J. (2018) · Cancer Research · doi:10.1158/1538-7445.am2018-3746 · Cited by 1 · see citing works

Authors: LABRIE, C., SIMARD, J., ZHAO, H. F., BELANGER, A., PELLETIER, G., & LABRIE, F.
Affiliations: Université Laval (CA)
ORCID: SIMARD, JACQUES
ZHAO, HUI FEN
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1989-06
Volume: 124
Issue: 6
Pages: 2745-2754
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo-124-6-2745
OpenAlex: W2084123371
Cited by: 80
References: 41
Citations by year: 2023: 1 · 2022: 1 · 2019: 1 · 2014: 3 · 2013: 1 · 2012: 5
FWCI: 10.69
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords: dehydroepiandrosterone, androstenedione, adrenal androgens, ventral prostate, androgen-dependent gene expression, dihydrotestosterone, castration, testosterone, androgen metabolism, prostate growth, DHEA sulfate
MeSH terms: Adrenal Glands, Androgen-Binding Protein, Androgens, Androstenedione, Animals, Autoradiography, Carrier Proteins, Dehydroepiandrosterone, Flutamide, Genes, Kinetics, Male, Orchiectomy, Prostate, Rats, Inbred Strains, Reference Values, RNA, Messenger, Sulfur Radioisotopes, Time Factors, Transcription, Genetic, Uteroglobin, Intracellular Signaling Peptides and Proteins, Rats, Secretoglobins, Mammaglobin B, Prostatein

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Stimulation of androgen-dependent gene expression by the adrenal precursors dehydroepiandrosterone and androstenedione in the rat ventral prostate.

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