PubMed Health⌕ Search

PubMed · 3584464

Circulating dihydrotestosterone may not reflect peripheral formation.

Abstract

We compared the blood (PBDHT) and urine (PUDHT) production rate of dihydrotestosterone (DHT) in normal men and women to determine whether peripheral formation was totally reflected in blood. PBDHT was similar when measured at both sites in men (674 +/- 79 vs. 788 +/- 207 SE micrograms/d); however, PUDHT was greater than PBDHT in women (174 +/- 55 vs. 55 +/- 8 micrograms/d, P less than 0.02). Excretion rates of DHT and 3 alpha-androstanediol (3 alpha diol) were similar in both sexes despite major differences in blood levels. However, between sexes large differences were present in 3 alpha diol glucuronide (3 alpha diolG) in both plasma and urine. These observations indicate that peripheral (renal) formation of DHT and probably 3 alpha diol were not accurately determined by measurement of these steroids in blood. The large difference between blood and urine production rates in women suggests an important role of non-testosterone precursors of 5 alpha-reduced steroids. Measurements of 3 alpha diolG may provide more insight into these peripheral events.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

V Toscano, R Horton. 1987. Circulating dihydrotestosterone may not reflect peripheral formation.. https://doi.org/10.1172/jci113003

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Neurosteroid modulation of recombinant rat alpha5beta2gamma2L and alpha1beta2gamma2L GABA(A) receptors in Xenopus oocyte.

GABA(A) receptors containing alpha(5)-subunit have an important role in cognitive function. As the agonistic effect of 3alpha-hydroxy ring-A reduced steroids depends on subunit combinations of the GABA(A) receptor, the antagonistic effect of pregnenolone sulfate and 3beta-hydroxypregnane steroids may vary between alpha(5)-subunit and alpha(1)-subunit containing receptors. We investigated the effect of agonist and antagonist steroids in the recombinant rat alpha(1)beta(2)gamma(2L) and alpha(5)beta(2)gamma(2L) receptors expressed in Xenopus oocytes using a two electrodes voltage-clamp technique. We did not find any significant difference in potency and efficacy of GABA response between alpha(1)beta(2)gamma(2L) and alpha(5)beta(2)gamma(2L) receptors. Compared to the alpha(1)beta(2)gamma(2L) receptor, a significantly lower degree of desensitization was observed in the alpha(5)beta(2)gamma(2L) receptor. In addition, the potencies of 3alpha-OH-5alpha-pregnan-20-one (3alpha5alphaP), 5alpha-pregnan-3alpha,21-diol-20-one (3alpha5alphaTHDOC) and 5alpha-androstane-3alpha,17beta-diol (3alpha5alphaADL) to enhance GABA response were significantly higher in the alpha(5)beta(2)gamma(2L) receptor, whereas their efficacies remained unchanged between two receptors. In either receptor, the efficacy of 3alpha5alphaTHDOC was significantly higher than 3alpha5alphaP and 3alpha5alphaADL. The efficacies of 5beta-pregnan-3beta,21-diol-20-one(UC1015) and 5alpha-pregnan-3beta,20alpha-diol(UC1019) to inhibit 30 microM GABA response, and the efficacies of 3beta-OH-5beta-pregnan-20-one (UC1014) and 5beta-pregnan-3beta, 20beta-diol (UC1020) to inhibit 3 microM 3alpha5alphaTHDOC+3 microM GABA response were higher in the alpha(5)beta(2)gamma(2L) receptor compared to the alpha(1)beta(2)gamma(2L) receptor. The potencies of pregnenolone sulfate and 3beta-hydroxypregnane steroids to inhibit the GABA response and the 3alpha5alphaTHDOC+GABA response did not vary between two receptors. Interestingly, the potencies and efficacies of pregnenolone sulfate and 3beta-hydroxypregnane steroids to inhibit the GABA response were positively correlated to their potencies and efficacies to inhibit the 3alpha5alphaTHDOC+GABA response. Results from the current study revealed a different modulation pattern by neurosteroids between the alpha(1)beta(2)gamma(2L) and alpha(5)beta(2)gamma(2L) receptor.

Androstane-3,17-diol↗

Studies on neurosteroids XVIII LC-MS analysis of changes in rat brain and serum testosterone levels induced by immobilization stress and ethanol administration.

The liquid chromatography-mass spectrometry (LC-MS) methods were developed and validated for the determination of testosterone (T) in the brain and serum of rats and of 5alpha-androstane-3alpha,17beta-diol (ADIOL), a metabolite of T, in the brain of rats. After derivatization of T with 2-hydrazino-1-methylpyridine and of ADIOL with p-nitrobenzoyl chloride, the detection sensitivities of T and ADIOL using LC-MS were increased 70- and 400-times superior to those of intact T and intact ADIOL, respectively. Those LC-MS methods are specific and reliable for the analysis of trace amounts of T and ADIOL in small amounts of samples. The animal studies using the developed methods showed that the brain and serum levels of T and the brain levels of ADIOL were not changed by stress or ethanol administration but the concentration ratio of the brain T to serum T in the stressed rats was higher than that in untreated rats. The low levels of endogenous AIDOL in brain of stressed and unrestrained rats found in this study demonstrated that the contribution to anesthetic and anxiolytic effects of ADIOL via gamma-aminobutyric acid type A receptors may be negligible.

Androstane-3,17-diol↗

Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.

CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1(-/-) mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen.

Androstane-3,17-diol↗