Date: Wed, 30 Apr 1997 12:42:17 +0300
From: Robinzon Boaz <robinzon@agri.huji.ac.il>
To: lupus-l@piper.hamline.edu
Subject: MED:Immune cells have specific receptors for DHEA
Message-ID: <1.5.4.32.19970430094217.00a055c4@agri.huji.ac.il>

Hi Guys,

Immune cells have specific receptors for DHEA, this means that DHEA is one
of the natural regulators of the immune response. Mind you that lupoids were
found to be low with DHEA.

TI:  The presence of a dehydroepiandrosterone-specific receptor binding
complex in murine T cells.
AU:  Meikle-AW; Dorchuck-RW; Araneo-BA; Stringham-JD; Evans-TG; Spruance-SL;
Daynes-RA
SO:  J-Steroid-Biochem-Mol-Biol. 1992 May; 42(3-4): 293-304
AB:  We have investigated the ability of dehydroepiandrosterone (DHEA) to
alter the production of interleukin-2 (IL-2) and to bind to a specific
binding complex in antiCD3 epsilon activated T cells. Binding activity
correlated with the presence of a specific DHEA binding complex in the
cytosol and nuclei of DHEA-responsive T-cell hybridomas, as well as in CD4+
and CD8+ cells isolated from peripheral lymph nodes of normal mice.
Scatchard analysis determined that intact lymphocytes and cytosolic
fractions contained high affinity binding for [3H]DHEA (approx. 2.6 nM) with
1000-7000 binding sites existing per cell. Five of the T-cell hybridomas
tested both responded to DHEA treatment with increased production of IL-2
and also contained specific high affinity [3H]DHEA binding. Four additional
T-cell hybridomas were found to contain no specific [3H]DHEA binding and
were also unresponsive to DHEA influences on IL-2 production. Sucrose
density gradients demonstrated a 3-4s [3H]DHEA binding complex in high salt
and a 7-8s binding complex in low salt. Specific binding was inhibited by
preincubation of the cytosol fractions with either trypsin or chymotrypsin,
or by heating to 60 degrees C for 1 h (less than 15% of control). [3H]DHEA
binding was unaffected by preincubation of the cytosol fractions with
ribonuclease, deoxyribonuclease, or phospholipase A. The DHEA-protein
complexes bound to DNA-cellulose with the amount of binding being slightly
increased by preincubation at 25 degrees C as compared to 4 degrees C. As
expected, [3H]DHEA binding was inhibited by the addition of unlabeled DHEA,
but was also modestly inhibited by dihydrotestosterone and cortisol. Binding
of DHEA was unaffected by progesterone, dexamethasone, estradiol,
androsterone, DHEAS, and beta-etiocholanolone at all concentrations tested.
DHEA was incapable of inhibiting the binding of [3H]DHT to the androgen
receptor or [3H]dexamethasone to the glucocorticoid receptor. Collectively,
these findings suggest that murine T cells contain a specific DHEA receptor.
We believe that DHEA is a steroid hormone that is directly involved in the
regulation of IL-2 production by both normal and some T-cell hybridomas.
--------------
Boaz
Rehovot, Israel
ROBINZON@agri.huji.ac.il