animalkrack3r
Member
- Awards
- 0
Maybe staying away from DHEA is a good thing?
(PA's post on bb.com)
It is well known that the dhea metabolite 5-ad is an active estrogen at physiological concentrations. apparently dhea ITSELF is as well, and according to this article even NORMAL levels can have just as much estrogen effect (on ERbeta) on the body as regular estrogens do at their circulating concentration. It also bound to the androgen receptor as an antagonist.
This bodes badly for DHEA supplementation, and inclusion of an aromatase inhibitor will have NO effect on the estrogenic fallout here since we are talking about direct receptor effects
Endocrinology. 2005 Nov;146(11):4568-76. Epub 2005 Jun 30. Links
Comment in:
Endocrinology. 2005 Nov;146(11):4565-7.
Direct agonist/antagonist functions of dehydroepiandrosterone.Chen F, Knecht K, Birzin E, Fisher J, Wilkinson H, Mojena M, Moreno CT, Schmidt A, Harada S, Freedman LP, Reszka AA.
Department of Molecular Endocrinology, Merck Research Laboratories, WP26A-1000, Sumneytown Pike, West Point, Pennsylvania 19486, USA. [email protected]
Dehydroepiandrosterone (DHEA) exhibits peak adrenal secretion in the fetus at term and around age 30 yr in the adult. Levels then progressively decline, which is associated with decreased levels of testosterone, dihydrotestosterone, and estrogen in peripheral tissues. DHEA supplementation in postmenopausal women increases bone formation and density, an effect mainly attributed to peripheral conversion to sex hormones. In this study, we tested DHEA for direct effects on the androgen (AR) and estrogen (ER) receptors. DHEA bound to AR with a Ki of 1 microM, which was associated with AR transcriptional antagonism on both the mouse mammary tumor virus and prostate-specific antigen promoters, much like the effects of bicalutamide. Unlike bicalutamide, DHEA stimulated, rather than inhibited, LNCaP cell growth, suggesting possible interaction with other hormone receptors. Indeed DHEA bound to ERalpha and ERbeta, with Ki values of 1.1 and 0.5 microM, respectively. Despite the similar binding affinities, DHEA showed preferential agonism of ERbeta with an EC50 of approximately 200 nm and maximal activation at 1 microM. With ERalpha we found 30-70% agonism at 5 microM, depending on the assay. Physiological levels of DHEA are approximately 30 nM and up to 90 nM in the prostate. DHEA at 30 nM is actually sufficient to activate ERbeta transcription to the same degree as estrogen at its circulating concentration, and additive effects are seen when the two were combined. Taken together, DHEA has the potential for physiologically relevant direct activation of ERbeta. With peak levels at term and age 30 yr, there is also a potential for antagonist effects on AR and partial agonism of ERalpha.
(PA's post on bb.com)
It is well known that the dhea metabolite 5-ad is an active estrogen at physiological concentrations. apparently dhea ITSELF is as well, and according to this article even NORMAL levels can have just as much estrogen effect (on ERbeta) on the body as regular estrogens do at their circulating concentration. It also bound to the androgen receptor as an antagonist.
This bodes badly for DHEA supplementation, and inclusion of an aromatase inhibitor will have NO effect on the estrogenic fallout here since we are talking about direct receptor effects
Endocrinology. 2005 Nov;146(11):4568-76. Epub 2005 Jun 30. Links
Comment in:
Endocrinology. 2005 Nov;146(11):4565-7.
Direct agonist/antagonist functions of dehydroepiandrosterone.Chen F, Knecht K, Birzin E, Fisher J, Wilkinson H, Mojena M, Moreno CT, Schmidt A, Harada S, Freedman LP, Reszka AA.
Department of Molecular Endocrinology, Merck Research Laboratories, WP26A-1000, Sumneytown Pike, West Point, Pennsylvania 19486, USA. [email protected]
Dehydroepiandrosterone (DHEA) exhibits peak adrenal secretion in the fetus at term and around age 30 yr in the adult. Levels then progressively decline, which is associated with decreased levels of testosterone, dihydrotestosterone, and estrogen in peripheral tissues. DHEA supplementation in postmenopausal women increases bone formation and density, an effect mainly attributed to peripheral conversion to sex hormones. In this study, we tested DHEA for direct effects on the androgen (AR) and estrogen (ER) receptors. DHEA bound to AR with a Ki of 1 microM, which was associated with AR transcriptional antagonism on both the mouse mammary tumor virus and prostate-specific antigen promoters, much like the effects of bicalutamide. Unlike bicalutamide, DHEA stimulated, rather than inhibited, LNCaP cell growth, suggesting possible interaction with other hormone receptors. Indeed DHEA bound to ERalpha and ERbeta, with Ki values of 1.1 and 0.5 microM, respectively. Despite the similar binding affinities, DHEA showed preferential agonism of ERbeta with an EC50 of approximately 200 nm and maximal activation at 1 microM. With ERalpha we found 30-70% agonism at 5 microM, depending on the assay. Physiological levels of DHEA are approximately 30 nM and up to 90 nM in the prostate. DHEA at 30 nM is actually sufficient to activate ERbeta transcription to the same degree as estrogen at its circulating concentration, and additive effects are seen when the two were combined. Taken together, DHEA has the potential for physiologically relevant direct activation of ERbeta. With peak levels at term and age 30 yr, there is also a potential for antagonist effects on AR and partial agonism of ERalpha.
Last edited: