PMID- 6458355
OWN - NLM
STAT- MEDLINE
DCOM- 19820222
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 41
IP  - 11 Pt 1
DP  - 1981 Nov
TI  - Estrogenic effects of physiological concentrations of 5-androstene-3 beta, 17 
      beta-diol and its metabolism in MCF7 human breast cancer cells.
PG  - 4720-6
AB  - 5-Androstene-3 beta, 17 beta-diol (ADIOL) has previously been shown to have a 
      high affinity for the estrogen receptor and to translocate it to the nucleus in 
      vitro and in vivo. This compound and related C19 delta 5-steroids of adrenal 
      origin have now been examined for their ability to induce the synthesis in MCF7 
      cells of an estrogen-dependent secreted glycoprotein (M.W. 46,000). 
      Concentrations required for half-maximum induction were 2 nM for ADIOL and 500 nM 
      for dehydroepiandrosterone (DHEA). Dehydroepiandrosterone sulfate showed weak 
      inducing ability at concentrations of 1 microM or greater. The induction by ADIOL 
      was unaffected by the presence of an aromatase inhibitor, and 5 
      alpha-androstane-3 beta, 17 beta-diol, which cannot be aromatized, also induced 
      the M.W. 46,000 protein at low concentrations. When cells were exposed to 10 nM 
      [3H]ADIOL, the cytosol and nuclear fractions contained [3H]ADIOL resistant to 
      charcoal adsorption. The bound [3H]ADIOL in the cytosol and nucleus was 
      displaceable by 17 beta-estradiol and tamoxifen, suggesting that it was binding 
      to the estrogen receptor. [3H]ADIOL was metabolized to its 3 beta-sulfate, which 
      was excreted into the medium, and to [3H]DHEA, which was found in the cells and 
      the medium as free DHEA and its 3 beta-sulfate. [3H]DHEA was also metabolized by 
      the cells to its 3 beta-sulfate, to free ADIOL, and to the 3 beta-sulfate of 
      adiol. We conclude that: (a) ADIOL is effective as an estrogen in MCF7 cells at a 
      concentration of 2 nM, which is within the range found in the blood of normal 
      women; and (b) sulfurylation is a major route of inactivation of 3 beta-hydroxy 
      delta 5-steroids in MCF7 cells.
FAU - Adams, J
AU  - Adams J
FAU - Garcia, M
AU  - Garcia M
FAU - Rochefort, H
AU  - Rochefort H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Androstenediols)
RN  - 0 (Glycoproteins)
RN  - 0 (Receptors, Estrogen)
RN  - 2DI9HA706A (Estrone)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 4TI98Z838E (Estradiol)
RN  - 95PS51EMXY (Androstenediol)
SB  - IM
MH  - Androstenediol/metabolism/*pharmacology
MH  - Androstenediols/*pharmacology
MH  - Biotransformation
MH  - Breast Neoplasms/*metabolism
MH  - Cell Line
MH  - Cell Nucleus/metabolism
MH  - Cytosol/metabolism
MH  - Dehydroepiandrosterone/metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Estradiol/blood
MH  - Estrone/blood
MH  - Female
MH  - Glycoproteins/biosynthesis
MH  - Humans
MH  - Receptors, Estrogen/*metabolism
EDAT- 1981/11/01 00:00
MHDA- 1981/11/01 00:01
CRDT- 1981/11/01 00:00
PHST- 1981/11/01 00:00 [pubmed]
PHST- 1981/11/01 00:01 [medline]
PHST- 1981/11/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1981 Nov;41(11 Pt 1):4720-6.