- Email: [email protected]
Binding of estradiol and progesterone in placentas and amniotic membranes
Volume Number
Correspondence
144
sary alarm in physicians placement dosages.
and in patients William
25701 Lakekznd Cleveland, Ohio
given subre-
McK.
Jefferies,
M.D.
Binding of estradiol and progesterone in placentas and amniotic membranes
1. Boyers, S. P., Buster, J. E., and Marshall, J. R.: Hypothalamic-pituitary-adrenocortical function during long-term low-dose dexamethasone therapy in hyperandrogenized women, AM. J. OBSTET. GYNECOL. 142:330, 1982. W. McK.: Safe Uses of Cortisone, Springfield, 2. Jefferies, Illinois, 1981, Charles C Thomas, Publisher, chap. 2, p. 12.
Reply to Dr. Jefferies To the Editors:
Dr. Jefferies his comments dexamethasone
Indeed,
has reemphasized concerning and other
our conclusions
long-term
low-dose
an important
the difference glucocorticoid
point in between therapies.
apply only to patients nightly
dexamethasone.
treated As we
stated in the discussion of our results, there is evidence that dexamethasone may be unique in that its clearance is variable among individuals and may sometimes be prolonged, leading to adverse effects not expected by the usual estimates of relative glucocorticoid potency and the concept of physiologic or replacement dose.‘, 2 On the other hand, there is evidence that small doses of glucocorticoids other than dexamethasone may produce similar impairment of the pituitary-adrenal axis, Dr. Jefferies’ experience notwithstanding.3 We purposely chose to be conservative, without being alarmist, in recommending that patients on long-term glucocorticoid therapy, including those on “physiologic” doses, be considered at risk for iatrogenic oversuppression. In practical terms we find Dr. Jefferies’ recommendation, that patients receiving regardless of dose, should have
ing times of increased with ours.
glucocorticoid therapy, the dose increased dur-
stress, essentially Stephen
79 .%tipps Suite 203 Sacramento,
3. Fujieda, K., Reyes, F. I., Blankstein, J.. and Faiman, C.: Pituitary-adrenal function in women treated with low doses of prednisone, AM. J. OBSTET. GYNECOL. 137:962, 1980.
Boulevard 44132
REFERENCES
with
363
3
in agreement P. Boyers,
M.D.
To the Editors:
In their recent article, Younes and co-workers (AM. GYNECOL. 141:170, 1981) reported the results of their study concerning the ability of human
J. OBSTET.
term placentas Specific receptor
to
bind proteins
estrogens for both
and progestins. hormones were
demonstrated in the cytosol by a radiochemical method. We evaluated’ the binding of estradiol (E,) and progesterone (P4) in frozen sections of human placentas and amniotic membranes with the use of a cytochemical technique. Ligand conjugates composed of 17/S estradiol and 1 la-progesterone covalently linked to bovine serum albumin and labeled with fluorescein isothiocyanate or rhodamine were used. We studied 18 cases from normal term pregnancies and one case from a spontaneous abortion at the fifth week of pregnancy. In three of these cases the placental tissue showed several areas of infarction. We found that placental tissue is able to bind both Ez and P4 in most cases, while amniotic membranes show a higher affinity for Ez than for Pd. The highest affinities for ES and P4 were found in the chorion and decidua, as shown in Table I; no binding was observed in the infarcted
areas.
The
samples
obtained
at
95825
REFERENCES 1. Meikle, A. W., and Tyler, F. H.: Potency and duration of action of glucocorticoids. Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function, Am. J. Med. 63:200, 1977. 2. Meikle, A. W., Clarke, D. H., and Tyler, F. H.: Cushing syndrome from low doses of dexamethasone: A result of slow plasma clarance, JAMA 235: 1592, 1976.
of
R. Arisio C. Benedetto G. F. Voglino M. Giai M. Massobrio
Drive California
5 weeks
pregnancy demonstrated strong binding in the cytotrophoblast and syncytiotrophoblast and in the decidua. The storage of sections at - 20” C for more than 1 week was followed by a progressive decay of the fluorescence associated with hormone binding. Our data together with those of Younes and associates suggest that binding of E, and P4 may play an important role in the growth and metabolism of the fetal-placental unit. Particularly, we consider it possible that E, and P4 receptors could mediate some effects of estrogens and progesterone on fluid transport across the amniotic membranes.*
St. Anna Hospital Department of Pathology Cso. Spezia 60 Torino, Italy Ist. Clinic of Obstetrics University of Turin Via Ventimigliu 3 Torino, Italy
and
and
Clinical
Gynuecology
Research
364
October Am. J. Obstet.
Correspondence
Table I. Estrogen receptors and amniotic membranes
(ER) and progesterone
Amnion r$exum
receptors
(PR) in human
Placental amnion
Chorion
placentas Syncytiotrophoblust
Decidua
1. 1982 Gynecol.
Intimal layer of chwiunic vessels
Sample No.
ER
PR
ER
PR
ER
PR
ER
PR
ER
PR
ER
PR
1 2 3 4 5 6* 7* 8 9* 10 11 12 13 14 15 16 17 18 19
+ + + + ++ + ++ ++ + + + + + ++ + + +
” ” + + + 2 + + -c a 2
+ + + + -c + +++ +++ ++ +++ +++ ++ ++ +++ ++ ++ +++ +++ NA
-+ + + + + ++ + ++ +++ + + ++
NA NA NA ++ + k 2 + + f
NA NA NA + -
N+A NA
;A NA
N+A +
N+A -
&i
NfA
:A
NA NA NA +++ ++ + + +++ ++ ++ + +++ +++ +++ ++ ++ +++ ++ +
NA NA NA t + + + ++ + ++ + ++ + + ++ ++ ++ + +++
NA NA NA ++ + + + ++ * + ++ +++ ++ ++ ++ ++ ++ ++ +++
NA NA NA 2 + + + + k + + ++ ++ + + + ++ ++ +++
NA NA NA NA NA NA NA + k ++ + + + + + + + NA
NA NA NA NA NA NA NA + + t + + t t ” + ? NA
&i
:A
+ , + + , + + + : Degrees of bright fluorescence; f : dull fluorescence; -: absence of fluorescence; NA: *Sample
with
placental
infarctions.
The
fluorescence
was present
REFERENCES 1. Arisio, R., Benedetto, C., Voglino, G. F., and Massobrio, M.: Dimostrazione di recettori per estrogeni (ER) e progesterone (PR) su membrane amniotiche e tessuto placentare per mezzo di ormoni marcati con fluorocromi, in Vecchietti, G. ,and Di Renzo, G. C., editors: I1 Liquid0 Amniotico: Fisiopatologia e Clinica, Padova, Piccin. In press.
and measured
only
in the normal
sample not available.
areas.
2. Benedetto, C., Monticelli, G., Corrias, M., Barbero, M., and Massobrio, M.: Effetti in vitro di estradiolo, estriolo e progesterone sul trasporto di acqua attraverso le membrane amnio-coriali umane, in Vecchietti, G. and Di Renzo, G. C., editors: 11 Liquid0 Amniotico: Fisiopatologia e Clinica, Padova, Piccin. In press.
Correspondence
144
sary alarm in physicians placement dosages.
and in patients William
25701 Lakekznd Cleveland, Ohio
given subre-
McK.
Jefferies,
M.D.
Binding of estradiol and progesterone in placentas and amniotic membranes
1. Boyers, S. P., Buster, J. E., and Marshall, J. R.: Hypothalamic-pituitary-adrenocortical function during long-term low-dose dexamethasone therapy in hyperandrogenized women, AM. J. OBSTET. GYNECOL. 142:330, 1982. W. McK.: Safe Uses of Cortisone, Springfield, 2. Jefferies, Illinois, 1981, Charles C Thomas, Publisher, chap. 2, p. 12.
Reply to Dr. Jefferies To the Editors:
Dr. Jefferies his comments dexamethasone
Indeed,
has reemphasized concerning and other
our conclusions
long-term
low-dose
an important
the difference glucocorticoid
point in between therapies.
apply only to patients nightly
dexamethasone.
treated As we
stated in the discussion of our results, there is evidence that dexamethasone may be unique in that its clearance is variable among individuals and may sometimes be prolonged, leading to adverse effects not expected by the usual estimates of relative glucocorticoid potency and the concept of physiologic or replacement dose.‘, 2 On the other hand, there is evidence that small doses of glucocorticoids other than dexamethasone may produce similar impairment of the pituitary-adrenal axis, Dr. Jefferies’ experience notwithstanding.3 We purposely chose to be conservative, without being alarmist, in recommending that patients on long-term glucocorticoid therapy, including those on “physiologic” doses, be considered at risk for iatrogenic oversuppression. In practical terms we find Dr. Jefferies’ recommendation, that patients receiving regardless of dose, should have
ing times of increased with ours.
glucocorticoid therapy, the dose increased dur-
stress, essentially Stephen
79 .%tipps Suite 203 Sacramento,
3. Fujieda, K., Reyes, F. I., Blankstein, J.. and Faiman, C.: Pituitary-adrenal function in women treated with low doses of prednisone, AM. J. OBSTET. GYNECOL. 137:962, 1980.
Boulevard 44132
REFERENCES
with
363
3
in agreement P. Boyers,
M.D.
To the Editors:
In their recent article, Younes and co-workers (AM. GYNECOL. 141:170, 1981) reported the results of their study concerning the ability of human
J. OBSTET.
term placentas Specific receptor
to
bind proteins
estrogens for both
and progestins. hormones were
demonstrated in the cytosol by a radiochemical method. We evaluated’ the binding of estradiol (E,) and progesterone (P4) in frozen sections of human placentas and amniotic membranes with the use of a cytochemical technique. Ligand conjugates composed of 17/S estradiol and 1 la-progesterone covalently linked to bovine serum albumin and labeled with fluorescein isothiocyanate or rhodamine were used. We studied 18 cases from normal term pregnancies and one case from a spontaneous abortion at the fifth week of pregnancy. In three of these cases the placental tissue showed several areas of infarction. We found that placental tissue is able to bind both Ez and P4 in most cases, while amniotic membranes show a higher affinity for Ez than for Pd. The highest affinities for ES and P4 were found in the chorion and decidua, as shown in Table I; no binding was observed in the infarcted
areas.
The
samples
obtained
at
95825
REFERENCES 1. Meikle, A. W., and Tyler, F. H.: Potency and duration of action of glucocorticoids. Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function, Am. J. Med. 63:200, 1977. 2. Meikle, A. W., Clarke, D. H., and Tyler, F. H.: Cushing syndrome from low doses of dexamethasone: A result of slow plasma clarance, JAMA 235: 1592, 1976.
of
R. Arisio C. Benedetto G. F. Voglino M. Giai M. Massobrio
Drive California
5 weeks
pregnancy demonstrated strong binding in the cytotrophoblast and syncytiotrophoblast and in the decidua. The storage of sections at - 20” C for more than 1 week was followed by a progressive decay of the fluorescence associated with hormone binding. Our data together with those of Younes and associates suggest that binding of E, and P4 may play an important role in the growth and metabolism of the fetal-placental unit. Particularly, we consider it possible that E, and P4 receptors could mediate some effects of estrogens and progesterone on fluid transport across the amniotic membranes.*
St. Anna Hospital Department of Pathology Cso. Spezia 60 Torino, Italy Ist. Clinic of Obstetrics University of Turin Via Ventimigliu 3 Torino, Italy
and
and
Clinical
Gynuecology
Research
364
October Am. J. Obstet.
Correspondence
Table I. Estrogen receptors and amniotic membranes
(ER) and progesterone
Amnion r$exum
receptors
(PR) in human
Placental amnion
Chorion
placentas Syncytiotrophoblust
Decidua
1. 1982 Gynecol.
Intimal layer of chwiunic vessels
Sample No.
ER
PR
ER
PR
ER
PR
ER
PR
ER
PR
ER
PR
1 2 3 4 5 6* 7* 8 9* 10 11 12 13 14 15 16 17 18 19
+ + + + ++ + ++ ++ + + + + + ++ + + +
” ” + + + 2 + + -c a 2
+ + + + -c + +++ +++ ++ +++ +++ ++ ++ +++ ++ ++ +++ +++ NA
-+ + + + + ++ + ++ +++ + + ++
NA NA NA ++ + k 2 + + f
NA NA NA + -
N+A NA
;A NA
N+A +
N+A -
&i
NfA
:A
NA NA NA +++ ++ + + +++ ++ ++ + +++ +++ +++ ++ ++ +++ ++ +
NA NA NA t + + + ++ + ++ + ++ + + ++ ++ ++ + +++
NA NA NA ++ + + + ++ * + ++ +++ ++ ++ ++ ++ ++ ++ +++
NA NA NA 2 + + + + k + + ++ ++ + + + ++ ++ +++
NA NA NA NA NA NA NA + k ++ + + + + + + + NA
NA NA NA NA NA NA NA + + t + + t t ” + ? NA
&i
:A
+ , + + , + + + : Degrees of bright fluorescence; f : dull fluorescence; -: absence of fluorescence; NA: *Sample
with
placental
infarctions.
The
fluorescence
was present
REFERENCES 1. Arisio, R., Benedetto, C., Voglino, G. F., and Massobrio, M.: Dimostrazione di recettori per estrogeni (ER) e progesterone (PR) su membrane amniotiche e tessuto placentare per mezzo di ormoni marcati con fluorocromi, in Vecchietti, G. ,and Di Renzo, G. C., editors: I1 Liquid0 Amniotico: Fisiopatologia e Clinica, Padova, Piccin. In press.
and measured
only
in the normal
sample not available.
areas.
2. Benedetto, C., Monticelli, G., Corrias, M., Barbero, M., and Massobrio, M.: Effetti in vitro di estradiolo, estriolo e progesterone sul trasporto di acqua attraverso le membrane amnio-coriali umane, in Vecchietti, G. and Di Renzo, G. C., editors: 11 Liquid0 Amniotico: Fisiopatologia e Clinica, Padova, Piccin. In press.