desensitized adenylyl cyclase and ..... enzymes involved in the conversion of proges- terone to aromatizable androgen. Effect ..... Potentiation by prolactin of the.
BIOLOGY
OF REPRODUCTION
32, 96-104
(1985)
Influence of High-Density Lipoprotein on Estradiol Stimulation of Luteal Steroidogenesis1 IQBAL
Y.-D.
KHANZ3
IDA
ALAIN
CHEN5
Department
of Physiology College
University
BELANGER,4
and GEULA
of Illinois
Department Le Centre
GIBORI3
and
Biophysics3
of Medicine
at Chicago Health Chicago, Illinois
Sciences
of Molecular Endocrinology4 Hospitalier de L ‘Universite Quebec,
Center,
Laval
Canada and
Department
of Medicine5
Sanford Palo Alto,
University California
ABSTRACT The
aim of this investigation was to determine whether luteal cells utilize cholesterol from high-density lipoprotein (HDL) for steroidogenesis and whether estrogen enhances utilization of exogenous sterol. Incubation of Day 15 corpora lutea (CL) with different human HDL resulted in a dose-dependent increase in progesterone production. HDL
enhanced
the overall
derived luteal doses of in vitro
steroidogenic capacity. However, the percentage of increases in 1 7o-hydroxy-
progesterone, testosterone and estradiol were significantly less than that of progesterone. Day 12 hypophysectomized and hysterectomized pregnant rats were treated with either estradiol, testosterone or vehicle for 72 h. Serum pregnenolone and progesterone were markedly increased by the steroid treatment, yet in vitro production of progesterone by CL in all the groups was similar. However, in the presence of HDL in the media, only luteal tissues from steroid-treated rats increased their progesterone output. The reduced production of progesterone by luteal cells of vehicle-treated rats was not due to an accumulation of pregnenolone but to an overall reduction in exogenous sterol utilization. In summary, results of this investigation suggest 1) luteal cells of pregnant rats effectively utilize cholesterol from HDL for maximal steroidogenesis, and 2) estradiol may stimulate luteal steroidogenesis, at least in part, by affecting the incorporation or utilization of cholesterol from HDL into the cell.
rat.
INTRODUCTION
The produces
corpus not
androgen
and
1976;
Gibori
1983;
Sridaran
to
be
the
luteum only estrogen
et a!.,
most
of the progesterone
and active
pregnant but
(Elbaum
1982;
Taya
Gibori,
and
and
1983)
steroidogenic
Days
rat also
organ
corpus
12 and
Keyes,
terone
appears
This tion
in the
tial nance September 11, May 4, 1984.
1984.
doubles
significantly
output
(Morishige
acquires a greater from androgenic increase appears
capacity substrate
Gibori
requirement
and
gism
11119.
‘Reprint requests: Dr. Iqbal Khan, Dept. of Physiology and Biophysics, College of Medicine, University of Illinoisat Chicago, Health Sciences Center, P0 Box 6998, Chicago, IL 60680.
of luteal
with (Gibori
1979)
and
half Greenwald, Estradiol
96
and independent
(Gibori 1973; increases
1978).
estradiol
function
prolactin
nancy
ond
between and
Roth-
increases its progeset a!., 1973) and to produce estradiol (Gibori et al., 1982).
Keyes,
for
by
Richards,
the
The
essenmainte-
pregnant
a number
shown
in
produc(Gibori
in the
in the
been well documented in which estradiol was
‘This work was presented in part at the 64th Annual Meeting of the Endocrine Society (Abstr. #398). It was supported in part by NIH grant HI)-
in size (Pepe
in size and in progesterone to be due to lutea! estradiol
et aL, 1977;
Accepted Received
luteum
15 of pregnancy
child, 1972),
Greenwald, and
The
to first
1978;
rat
has
of studies act half
Gibori
in of
synerpreg-
et al.,
of prolactin in the secet a!., 1977; Takayama and Ochiai and Rothchild, 1981). progesterone synthesis with-
ESTRADIOL,
out
affecting
the
metabolism
child
1980;
Belanger
low
and
LH
estrogen
and
receptor by
to
nancy,
which
terol
synthesized
thesis
both
appear de of in
vivo and
1982;
Schuler
et
in conjunction of high-density receptors in
and
from and
steroidogenic
important
may
increase
to the
HDL.
This
larly
attractive
et
al., al.,
possibility
estradiol
rats
cells,
Incubat
lutea
it
from
be a particuhas
the
Serum
Lipoprotein
cholesterol
of
derived
hormone action
examined from
biosynthesis, on
luteal
exogenous
HDL
and cell
supply
of
possibilities
pregnant
2)
function
1)
rats
utilize
for
steroid
that
Human nonpyrogenic,
to
the
Beckman
sterol.
MATERIALS
AND
METHODS
Day
tomized
stereotaxic tomy was the time remnants
Hormonal
of in
operation the fossa
approach
and the Steroids
using
a
of hypophysecof the pituitary at
the
recovery and by at autopsy.
of
Extraction
rats were hypophysec-
Completeness the
from each individual rat were at 37#{176}Cin 1 ml of freshly CO,) Medium 199 containing Grand Island, NY). Following was terminated by placing the
Preparation
60 Ti rotor at 45,000
rpm
for 20 h. The
absence of Rats showing
any in-
Millipore gentamycin
filter,
placed
in a
(10 Mg/mI) and migrated as a single band on 5%
gel electrophoresis HDL used has et al. (1984).
and Purification
One ml of medium
a transauricular
instrument. judged by
agarose sition Reaven
Treatment
12 of pregnancy,
through
adhering
(d=1.090-1.215) pooled human
stored at 4#{176}C. HDL
Pregnant Sprague-Dawley rats were purchased from Holtzman Co. (Madison, WI) and were housed under controlled environmental conditions with 14 h light per day at 24#{176}C.Purina Rat Chow and tap water were available ad libitum. The day sperm was present in the vagina was designated as the firstday of pregnancy.
On
HDL
passed through a 0.45-Mm sterile tube containing
and
from
final lipoprotein fractions were dialyzed exhaustively against 0.9% NaCI, 5 mM Tris, pH 7.4, and concentrated by loosely packing the outside of the dialysis bag with Aquacide. The concentrated samples were
Animals
Operations
free
were isolated from plasma by sequential centrifugation (Havel et al.,1955) using solid KBr for density adjustment (Radding and Steinberg, 1960) in a
estrogen’s
is related
dissected
a stereomicroscope.
sample vials in an acetone-dry ice bath. Samples were stored at -20#{176}C until processed for radioimmunoassay
been
1984).
lutea
15 of
ions
analysis.
we
were
tissue under
(RIA)
Thus
Day
Preparation
Three corpora lutea cut in half and incubated gassed (95% 0, and 5% 25 mM Hepes (Gibco, incubation, the reaction
estradiol
estradiol
and corpora
of HDL receptors rats (Gibori et al.,
corpora
killed on
15, rats were killed with an overdose of the ovaries were quickly removed. Indi-
found to increase the number in luteal cells of pregnant that
The third group received Control rats were intact
the
cholesterol to
Tissue
Day
nonluteal
orig-
luteal
whether
since
ether vidual
luteal
affects
of
appeared
one,
for
and
On
steroidogenesis
of
daily. oil).
progroup (100
of Blood
Autopsy
the possibility used
ascertain
to
observation,
(HDL)-specific of pregnant
utilization
designed
A 0.75-mi sample of blood was collected daily between 0900-1100 h by tapping the jugular vein through the skin under ether anesthesia. The serum was collected and stored at -20#{176}C until assayed.
characterization
capacity
were
animals. Rats were
Collection
biosynet
supports
Because
and
al.,
exoge-
Bruot
substrate
mm)
pregnancy.
(Azhar
This
3.18
ml sesame oil) (0.25 ml sesame
pregnant
vitro
recent
and
an
steroid
lipoprotein corpora lutea
HDL.
was
Mg/O.25 vehicle
1981;
1981). the
et
utilize
in
al.,
with
biogenesis
inates
size
choles-
(Kovanen
o.d.
surface area of 100 mm’. Another received subcutaneous injections of 1713-estradiol
of preg-
lutea
for
Menon
cholesterol
membrane size
novo ovaries
et al., 1984),
the
602-305, vide a
an
in
principally
cholesterol
Azhar
that
to
both
corpora
to use rat
1981;
(Gibori
increasing
rabbit
luteinized
source
AMP
cyclase
respond
97
Silastic capsules filled with testosterone were implanted s.c. in the dorsal part of the neck. These capsules were prepared from Dow-Corning (Midland, MI) Silastic medical grade tubing (cat. no.
of
secretion.
contrast
nous
independent
content
challenge
1978),
unpub-
hormone (LH)-cyclic desensitized adenylyl
progesterone In
Gibori,
STEROIDOGENESIS
complete hypophysectomy were excluded from the experiment. Hysterectomy was done through a midline abdominal incision. Immediately after the operations, rats were divided into three groups, each group consisting of 5-8 rats. In one group of rats, 1-cm long
Roth-
(Sridaran et al., 1983) also augments the in
of progesterone
the luteinizing system. CL with
LUTEAL
to
and
and
Our recent work that estradiol
production
vivo
(Rodway
Khan,
AND
of progesterone
20a-hydroxyprogesterone
lished). indicates
HDL
(Nobel, 1968). been previously
The comporeported by
of Steroids
was extracted solvent was evaporated were separated on LH-20
twice with ether under nitrogen. columns before
measurement as previously reported (Belanger et al., 1979). Briefly, LH-20 columns (lx 10 cm) were packed and washed with 25 ml of benzene-methanol. They were then washed with 20 ml of the firstsolvent system used for elution (isooctane-benzene-methanol;
98
KHAN
90:5:5,
by volume).
Calibration of LH-20
columns
was performed following known tritiated steroids
addition of 10,000 cpm of to aliquots of the methanol extract and collection of 1-mI samples. Progesterone
elutes firstin Fractions 6 to 12. Pregnenolone is found in Fractions 13 to 24, while testosterone and 17ahydroxyprogesterone elute in Fractions 28 to 42. The polarity of the solvent was then changed to 62:20:18 for the elution of estradiol.
ET
AL.
progesterone nant rats, 15
ml
pregnant medium
trations ml
for pregnenolone,
17-hydroxyprogester-
one, testosterone and estradiol were performed after chromatography using highly specific antisera. The specificity, validity and reliability of these RIAs have been previously described (Belanger et al., 1979). Progesterone was assayed with or without chromatography by two different RIAs (Gibori et al., 1977; Belanger et al., 1979).
little
Analysis
increased
ng.corpus
luteum’#{149}3
crease
in HDL
used to determine treatment groups. A
P
Student’s test were
significant differences between value below 0.05 was considered
significant.
Effect
from of
Production To
HDL
on
Progesterone
by Luteal evaluate
Cells
increase of HDL
of Pregnant
the role of HDL
Rats
in supporting
Day
The
15
medium
with
protein.
Media
progesterone,
Luteal
500
or were
335
greatest
in-
pg
when
protein/mI.
increased
there
no
was
con-
secretion.
Steroidogenesis
the effect of corpora pregnant
as
HDL of
occurred
in progesterone on
of value
were
protein/mi
,yet of
Progesterone
concentrations
To examine steroidogenesis
RESULTS Effect
was
1
by HDL
presence
function
h’.
concentration
pg
of
a maximal
secretion
500
comitant
a
Fig.
h
the
progesterone
HDL
absence
protein/mi. as
reaching
1
protein! in
luteum’.3 in
I-IDL
concentration,
beyond
Values presented are the mean ± SEM. test, analysis of variance and Kruskal-Wallis
pg
pregDay
secretion
the
significantly
secretion
When Statistical
in
± 11 ng.corpus
as 65
pg HDL depicted
progesterone
maintained
increased
the
0-1000
Results
that
135
luteal cells of obtained from
maintained for 3 h in HDL in various concen-
from
medium.
indicated was
Assays
by lutea
rats were containing
ranging of
tissue RIA
secretion 3 corpora
of HDL lutea, rats
without assayed
on the overall tissues obtained
were
incubated
500
pg
for
in
of
HDL
pregnenolone, testos-
1 7ct-hydroxyprogesterone,
400-
300-J
C) C
w
200-
C
0 I-
a, Co
a’ 0)
0
100-
I-
0I 0
I
65
I
125
I
250
h-HDL
500
(jiG
1000
Protein/ML)
FIG. 1. Effect of various doses of human high-density lipoprotein (h-HDL) on progesterone production by corpora lutea (CL) of pregnant rats.Three corpora lutea were isolated from Day 15 pregnant rats, cut in half, and incubated in the presence of HDL at 37#{176}C for 3 h. Progesterone was analyzed in the medium. Each point represents the mean ± SEM of values from 5 rats.
ESTRADIOL,
HDL
AND
LUTEAL
99
STEROIDOGENESIS
terone
and
indicate
estradiol.
Results
depicted
that in the presence
in
of HDL
Fig.
2
the overall
steroidogenic capacity of the luteal cell was enhanced. However, the percentage increase in
300
I-
1 7a-hydroxyprogesterone,
testosterone
and
es-
Ui
tradiol
was
less than the increase in This suggests that the
significantly
‘Ii
progesterone
production.
limiting
200
luteal
I
factor cells
enzymes terone
for is
the
involved
testosterone
production
by
activation
of the
in the conversion
of proges-
stage
to aromatizable
of
androgen.
ioo Effect of Estradiol and Testosterone Administration on Progesterone and Pregnenolone
Production
As depicted
In
Vivo
in Figs. 3 and
and
pregnenolone
and
FIG. 2. Effect of HDL on steroidogenesis by isolated corpora lutea (CL). Three corpora lutes were isolated from each day 15 pregnant rat and were incubated in the presence or absence of h-HDL (500 g protein/ ml) for 3 h. Steroids were analyzed in the media as described in Materials and Methods. Levels of steroids
cantly
reduced
in hypophysectomized-hysterec-
tomized ment
rats with
in the absence of HDL
circulation.
noo
(PREG),
7
±
1 ng/CL;
TEST
170-01W
ESTR
were as follows: pregnonolone progesterone
(PROG),
134
±
30 ng/CL; 17a-hydroxyprogesterone (l7cs-OHP), 160 testosterone (TEST), 70 ± 37 pg/CL; estradiol (ESTR), 86 ± 34 pg/CL. Values are mean ± SEM of observations obtained from 5-8 rats. pg/CL;
testosterone progesterone vivo,
corpora
that
progesterone
received
sustained
dramatically and pregnenolone In contrast lutea
of
only.
Treat-
levels peripheral
results obtained vehicle-treated
of
signifi-
estradiol
increased in the to
of
Vitro levels
were
vehicle levels
In
4, serum
or
of in rats
secreted as much progesterone and pregnenolone in vitro as the luteal tissue of rats treated with steroids.
60
10
E
I.
60
w z
50
UI5
40
z4
z 0 -J 0
0
w I-. 0)
E C
C
UI
UI
I
30
a-
20
UI 0)
10
C
ii V
4 E
T
FIG. 3. Effect of in vivo treatment of estradiol or testosterone on serum levelsof pregnenolone and progesterone. Rats were hypophysectomized and hysterectomized on Day 12 of pregnancy and treated from Day 12 through Day 15 with either vehicle (V), a 1-cm capsule filled with testosterone (7) or with 100 g of estradiol daily (F). Intact pregnant rats were used as controls (C). On Day 15 blood was collected and progesterone and pregnenolone were analyzed as described in Materials and Methods. Each bar represents the mean ± SEM. The number at the base of each bar refers to the number of determinations.
KHAN
100
ET
AL
150
140
-
120
2
12
-J
o
a
100
10
Ui
z
a
80 S
4
20
2
C
V
E
I
FIG. 4. Effect of in vivo treatment of estradiol or testosterone on subsequent in vitro secretion of progesterone or pregnenolone. Rats were treated as described in the legend of Fig. 3. On Day 15 corpora lutea (CL) were isolated and incubated for 3 h. Progesterone and pregnenolone were analyzed in the incubation media as described in Materials and Methods. Each bar represents mean ± SEM and the number at the base of each bar designates the number of animals.
Effect
of HDL
Lutea and
and
manner.
Corpora
previous
on Progesterone
Pregnenolone
Production
of Rats
by
Treated
with
HDL
Estradiol
determine
whether
luteal
estradiol
affects
HDL incorporation into luteal cells and to find out if the stimulatory effect of estradiol could be demonstrated in the presence of exogenous HDL, with
corpora lutea either steroids
obtained or vehicle
from were
rats treated incubated in
the presence of 500 pg of HDL protein/mi for 3 h. Addition of HDL to the medium had little effect on progesterone production by corpora lutea of rats that received
vehicle only (Fig. 5).
In contrast,
of HDL
the presence
increased progesterone lutea of steroid-treated whether
the reduced
by corpora to an capacity
dramatically
production animals.
production
To
by corpora determine
of progesterone
lutea of vehicle-treated
rats was due
accumulation of pregnenolone, the of luteal tissue to increase pregnenolone
output in the presence of HDL was determined. The data (Fig. 5) revealed that pregnenolone production was similarly increased in all groups in the presence
of HDL.
The production
on
the
present
findings
cholesterol in
increases a
dose-dependent
to
combined
with
of specific
luteal
plasma
bind
and
indicate luteal
that
HDL-
progesterone and
saturable
metabolize
our
receptors
membrane
for
(Gibori
et
of pregnant machinery
lipoprotein.
3-hydroxy-3-methylglutaryl
Although
coenzyme
A reduc-
tase activity is substantial in this tissue (Khan et al., 1983), corpora lutea failed to secrete progesterone This
maximally
indicates
that
synthesize
in luteal
cholesterol
in
the
absence
of
cells
of
pregnant
vitro
at
a rate
HDL. rats that
is
inadequate to support maximal steroidogenesis. In fact, not only is progesterone production enhanced
by
overall Corpora output
the
in
these
comparison to one production. previous
findings
activation conversion
Thus,
HDL
but
is
increased.
is
indicate
testosterone substrate
rats
and formation is dependent
substrate earlier
estradiol of the limited
observations
that
the
synthesis but also
of the enzymes of progesterone
androgenic our
steroids
the
in
3-fold increase in progesterThese results corroborate our which
(Sridaran estradiol
of pregnant
two
the
limiting step for only progesterone
of
of
pathway
lutea increase testosterone and by 50%. However, the magnitude
increase
of the
presence
steroidogenic
androgen contrast,
DISCUSSION carried
findings,
al., 1984), indicate that luteal cells rats are equipped with the necessary
Testosterone To
These
demonstration
rate-
is not the stage
responsible to aromatizable Gibori, by
1983). corpora
on the (Gibori
et that
for In lutea
availability al., activation
1982). of
ESTRADIOL,
HDL
LUTEAL
AND
500
STEROIDOGENESIS
101
PREGNENOLONE
-I
I
400 UI C)
z
UI 0) UI
300 UI
I
I-
z UI
20O UI
‘.2
z
.1i:i
100
V
E
I
V
E
T
FIG. 5. Effect of h-HDL on progesterone and pregnenolone production by corpora lutes of rats treated with estradiol or testosterone. Rats were treated as described in the legend to Fig. 3. On Day 15, three corpora lutea were isolated and incubated for 3 h in the presence or absence of h-HDL (500 g protein/mi). Progesterone and pregnenolone were measured in the incubation media. Values are mean ± SEM with the number of animals at the base of each bar.
the enzymes progesterone chorionic increases
involved in to testosterone
gonadotropin the capacity
testosterone respectively,
conversion of with human
the
(hCG) of luteal
and estradiol in media devoid
administration cells to produce
10and of HDL
200-fold, (Sridaran
treatment
of
either
estradiol
or
and Greenwald, 1973; Rodway 1982). The results indicate that
and HDL tion
Gibori, 1983), whereas incubation with has only a limited effect on the producof both steroids (Fig. 2). These results sug-
testosterone not only secretion
gest nous
that although source of
ences vehicle-
found in vivo, or steroid-treated
corpora rats
specific
levels
of
and
remains
incubated of luteal
the availability cholesterol is
steroidogenesis, enzymes
the
an important Since cholesterol
activation
the
in
synthesis,
as
pathway
in steroid
biosynthesis.
cells derived
of pregnant rats also utilize from HDL for steroid
reported
for
serum gonadotropin-hCG-treated al., 1981; Azhar and Menon, 1982; Schular et al., 1981), determine whether estradiol tion of cholesterol from were obtained hypophysectomized Day
12.
tase et
cal
These
enzyme(s) al., doses
from
of
lutes and
highly
mare’s
rats (Azhar et 1981; Bruot et al.,
Day 15 pregnant and hysterectomized
corpora
estradiol,
pregnant
it was of interest to affects the utilizaHDL. Corpora lutea
(Elbaum
are
1981),
of some
steroidogenic
step luteal
of an exogeimportant for
are Keyes,
sensitive and
respond
rats on
progesterone in the cells
luteal
and Garris, estrogen or
lutea produce
of
pregnenolone
of HDL. vehicle-treated
The
either similar when
capacity rats to
as luteal cells be related to sterol (Gibori
of its et
al., 1984), which may be capable of supporting steroidogenesis in lipoprotein-deficient media. Thus, progesterone production in the absence of HDL capacity
may not of luteal
of different commencement
the
between of
to the steroidogenic due to the presence
of steroid of
production by others Terranova
be related cells but
amounts
discrepancies
vivo
absence from
secrete as much progesterone steroid-treated animals may higher storage of preformed
1976; Azhar to physiologiin
in
(Gibori et Takayama
administered to these rats increases progesterone but also pregnenolone in vivo. However, despite the differ-
rich in aroma-
to
aromatizable
androgen with a dramatic increase weight and progesterone production al., 1977; Gibori and Keyes, 1978;
have and
at the Similar
the in vivo and
progesterone
(Takayama and Greenwald,
precursor
experiment.
been
Greenwald, 1981). Corpora
in vitro reported 1973; lutea
KHAN
102 which
cease
the
end
to
treatment
were
terone in very active
found
progesterone
in vivo
or after LH
antiserum
to produce
lipoprotein-deficient corpora lutea
yams and Greenwald, tained lutes
secrete
of pregnancy
Greenwald, 1981). In
progesterone
administered suggesting
of
one
production
by
or utilization cells, delivery The HDL
of
and for
of
affecting
the
thus allowing steroidogenesis.
vehicle-
HDL
does not seem apolipoprotein
substrate
and Hesse, proposed HDL
to require degradation
1980). Winkel that cholesterol particle
depending movement
into
et the
on the force of cholesterol
cell
from How-
complete (Gwynne
al. may
(1980) move
have from
vice
and
versa
action. Net cell may be
of mass into the
possible only in cells which actively catabolize cholesterol. Based on the in vivo results, it can be envisioned that corpora lutea of rats treated with steroids are increasing in size and actively producing progesterone, and thus ously metabolizing cholesterol for ogenesis and membrane biosynthesis.
are both
continusteroidThus, an
increase in HDL-cholesterol incorporation occur. However, the finding that corpora of vehicle-treated rats secrete as much terone
in vitro
as corpora
rats strongly cholesterol-HDL to
an
increased
measuring [Iiiodo-HDL corpora (Gibori
lutea
lutea et al.,
increase is not solely
number in the
catabolism.
By
of binding sites plasma membrane
of pregnant rats, we 1984) provided direct
that estradiol increases receptors. Thus, estradiol
the number appears to
steroidogenesis
a
through
in due
the
cholesterol
the
may lutes proges-
of steroid-treated
suggests that incorporation
of of
previously evidence of HDL stimulate
mechanism
gives rise to an increase in the number receptors in the plasma membrane.
steroidogenic the pregnant receptors
precursors. The direct correlation activity
rat previously
and
present between
(Gibori
et
triples progesterin the presence the may
effect
but
and et al.,
on
may
also
since estradiol in luteal cells
affect
Both
hormones
on
in the
luteal
Hwang both
et al., 1981; Strauss appear to promote
cell
receptors
(Gibori
et al.,
(Azhar et production.
progesterone
nisms
of
totally
action
of
different.
by cyclic dent of
AMP,
the
maintains
al.,
two
LH
and increase the mechahormones
action
adenylyl
cyclase
responsiveness
its
from
et al., 1983). It remains whether both hormones act
adenylyl
to induce/activate for steroidogenesis. the corpora
cholesterol
steroidogenesis estradiol may sis,
on
at least
cyclase to be detervia different
the
proteins
results lutea
of this investigation of pregnant rats can
from
HDL
and stimulate in part,
to
1983); howis indepen-
(Sridaran mined
utilize
effect
al.,
dent
In summary, indicate that
are
is mediated
the effect of estrogen is indepencyclase system. Luteal estradiol
LH in luteal cells (Sridaran et ever, its action on steroidogenesis
messengers responsible
and of
and Boyd, the incorlipoprotein-
1981), However,
these
While
1984;
et al., 1982) the conversion
cholesterol to pregnenolone (Leaver 1981; Toaff et al., 1983), accelerate poration and the metabolism of cholesterol
function.
lipoprotein
membrane
rats
the effect of LH
luteal
increase cell
choles-
pregnant
that
of to
also depletes of hypophysec-
to compare
estradiol
lipoprotein The effect solely due
hysterectomized 1984).
of
action of be largely
further luteal by
affecting
tion of cholesterol from thus possibly allowing delivery for steroidogenesis.
for
maximal
indicate that cell steroidogene-
HDL into increased
the
incorporathe
cell and substrate
ACKNOWLEDGMENTS
study the
of the corpus luteum the levels of lipoprotein reported
its
with
which of HDL In this
fashion, the supply of cholesterol to the rat luteal cells is optimized to meet the demand for steroidogenic suggests a
by
uptake
tomized (Gibori
the
and
cholesterol delivery. not, however, be
It is interesting
into
increased
and may
terol utilization cholesterol ester
incorporation
from
for
receptors estradiol lipoprotein
of HDL, progester-
estradiol in vivo
in vitro suggests that on luteal cell function
accounted
and ob-
mechanism of cholesterol uptake is not yet completely understood.
ever, it lysosomal
the
those
cholesterol
(Taka-
corpora markedly
the presence stimulates
1984). The fact that one production both of HDL estrogen
than
Terranova to results
media, produced
than
animals in that estradiol
proges-
medium pregnancy
1973; contrast
in lipoprotein-deficient of steroid-treated rats
more
more
at
ET AL.
We are grateful to Dr. G. D. Niswender, Colorado State University, for the progesterone antiserum, to Rosemary Ciepper and Linda Alaniz for animal care, and to Suzanne Glass for the preparation of the manuscript. The expert editorial assistance of Linda Glaser is also gratefully appreciated. REFERENCES
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in
