Effect of dexamethasone on prolactin secretion in late pregnancy ANTTI
KALJPPILA
MATTI
PUUKKA
RISTO
TUIMALA
Oulu, Finland It is established that PRL secretion is regulated by estrogens. Glucocorticokts, on the other hand, suppress estrogen secretion during pregnancy and may also inhibit PRL by direct hypothalamopituitary action. In this study PRL and estradiol were determined with specific radioimmunoassays in 14 women during gestational weeks 28 to 34 prior to, during, and following short-term intramuscular dexamethasone administration (12,8, and 4 mg on three consecutive days) used for prophylaxis of RDS in preterm infants. There were no s(gnificant alterations in PRL serum concentrations; estradiol showed a significant drop (P c 0.001) during all 3 days of treatment, returning to the pretreatment tevet on posttreatment day 1. The PRL and TSH responses to 200 pg of intravenous TRH on day 2 or 3 of dexamethasone treatment in six women during late pregnancy were not inhibited. Short-term dexamethasone treatment with pharmacologic doses does not suppress the physiologic secretion and release of PRL or the release induced by TRH during late pregnancy. (AM. J. OBSTET. GYNECOL. 1341752, 1979.)
IS MUCH evidence supporting the importance of estrogens in the physiologic regulation of prolactin (PRL) secretion in man. A parallel exists in the increase of estrogen and PRL secretion in girls at puberty’ and their decrease in aging women2 The increased circulating level of estrogens either during pregnancy3 or when induced by exogenous estrogen administration” is accompanied by a parallel rise in PRL secretion. In animal experiments the administration of estrogen resulted in increased mitotic activity of pituitary lactotropes in addition to the rise in PRL secretion,5 indicating that estrogens have an activating function directly on the pituitary cells secreting PRL. It is well known that exogenous glucocorticoids suppress the biosynthesis of estrogens63’ and consequently might modify PRL metabolism. Because short-term glucocorticoid therapy is widely used in the prevention of the respiratory distress syndrome (RDS) of preterm infants, this study aims to evaluate the influence of such THERE
From the De#wtment.s of G9necology and Obstetrics, Clinical Chemictry, University of Oulu. Receivedfor Accepted
publication September
June
6, 1978.
22, 1978.
Rejnint requests: Dr. Antti Kau@la, Obstettics and Gynecology, University Oulu, 90220 Outu 22, Finland.
752
and
Department of Central Hospital
of
therapy on either physiologic or thyrotropin-releasing hormone (TRH)-induced secretion of PRL. Paeflts
and -s
of patients. Twenty patients were treated with intramuscular dexamethasone for 3 days (12, 8, and 4 mg consecutively at 8:OOA.M.) in order to accelerate fetal pulmonary maturation. The ages of the patients ranged from 17 to 40 years (mean 27.5) and parity from I to 3 (mean 1.9). The threat of premature delivery was due to placenta previa in three cases and to premature uterine contractions in the other 17 cases. Two cases of mild pre-eclampsia, one of jaundice of pregnancy, and one of Rh incompatibility were diagnosed previously. The dexamethasone therapy was administered between gestational weeks 28 and 34 (mean 32.1) and all infants detivered between gestational weeks 34 to 42 (mean 37.4) were healthy. Perfonnaeice of the t&I, The basal secretion of PRL and estradiol was followed in 14 cases. Venous blood samples were drawn at 8:OO .&.M. and 4:OO P.M. from day 2 preceding dexamethasone treatment to day 2 after therapy. Estradiol was assayed only from afternoon samples; PRL was determined from both morning and afternoon specimens. The response of PRL and thyrotropin (TSH) t.o TRH was evaluated in six women who volunteered for Charactwization
0002-9378/79/150752+04$00.40/0
0
1979 The
(.. L. Mosby (.o
Volume Number
134 7
Effect
Table I. The mean (?S.E.M.) values of prolactin and thyrotropin prior administration of 200 pg of TRH in women treated with intramuscular control subjects during the third trimester of pregnancy Prolactin
Dexametharione
Healthy pregnant The
treated
Basal (N = 6)
controls (N = 9)
to and following dexamethasone
(pgIL) After
Patients
of dexarnethasone
20 min
209 + 24
450
210 + 10
429 2 28***
+- 39***
injection
Results Serum PRL and estradiol durhtg dexamethasone therapy. The mean (?S.E.M.) PRL level prior to dexamethasone administration (151 * 10 PgIL) did not differ significantly from the maximally changed level (133 -+ 11 pg’L) which was recorded on day 2 of ther-
secretion
(U/L) After
injection
60 min
Basal
20 min
60 min
287 _’ 22*
11.6 f 0.7 9.8 2 0.8
19.4 rf: 2.2*** 18.9 2 1.8***
17.0 2 2.1** 19.5 +- 1.9**
311 f 18*
753
the intravenous and in healthy pregnant
Thyrotropin
degrees of significance are calculated from the basal values: * = p < 0.05,
this study after receiving detailed information. After an overnight fast on the second (4 patients) or third (2 patients} day of dexamethasone treatment, an intravenous cannula was inserted at IO:00 A.M. The first blood sample was ‘drawn 30 minutes later, followed immediately by a bolus of 200 pg of TRH. The other specimens were taken 20 and 60 minutes after the TRH injection. Assays and evaluation of the results. The blood samples were centrifuged immediately and the serum was stored ;at -20” C. Estradiol was determined by means of a specific automated radioimmunoassay (RIA) which has recently been described in detail8 PRL and TSH were assayed with specific homologous RIA’s with CEA-IRE-SORIN kits (Department des Radioelements, 91190 Gis-sur-Yvette, France). All the samples were assayed in the same batch, and the within-assay variation was 7% for PRL and 8% for TSH. The reference PRL was standardized against the research Standard A for human PRL, 711222, obtained from the division of Biological Standards, National Institute for Medical Research, London; 40 IU of this standard were found to be equivalent to 1 ng of immunochemical human PRL, Friesen No. 1, which was supplied by the NIAMDD. The TSH reference preparation was First IRP MRC 68/38. All determinations were made in duplicate. The results are given as both absolute and relative values, the latter being calculated from the mean level prior to the dexamethasone treatment and in the TRH test from the intial level, according to the formula .. value - mtttal value x loo. initial value
on PRL
** = p < 0.01, *** = p < O.OOI.
apy at 4:00 P.M.-a decrease of 12.5% (Fig. 1). Relative estradiol values, on the other hand, were significantly lowered on all 3 days of therapy (p < 0.001). The mean basal level of estradiol was 19.8 * 3.3 pg/L, and the lowest value obtained (12.0 + 2.7 PgIL) was on day 2 of therapy. The return to initial levels was recorded on day 1 after therapy. PRL and TSH responses to TRH. The circulating levels of both PRL and TSH increased after TRH injection in each of the six women tested during dexamethasone treatment as well as in nine healthy control subjects examined during the last trimester of pregnancy (Table I). The significant rise in PRL level in the dexamethasone group at 20 and 60 minutes did not differ from the corresponding results In the control subjects. The significant changes in the level of TSH in the dexamethasone group at 20 and 60 minutes were similar to those in the control subjects.
Comment Antepartum glucocorticoid therapy for the prevention of RDS in preterm infants has been widely accepted since Liggins and Howies in 1972 proved it to be beneficial in a controlled clinical trial. The effect of glucocorticoids is probably mediated by the induction of phosphocholine transferase.‘O Because the increase in the endogenous fetal cortisol is not a necessary antecedent of augmented surfactant synthesis,“, ” and because the reduction of RDS is found only in infants ivhose mothers were treated during a certain gestational period, there seems reason to conclude that glucocorticoids have only a permissive role in fetal lung maturation. Recently it has been reported that the incidence of RDS among infants whose cord plasma level of PRL is less than 200 rig/ml was significantly higher than among those with PRL concentration higher than 200 rig/ml.‘* It has been suggested that an augmented surfactant formation, lung maturation, and increased PRL level are causally related. The effect of PRL is believed to be mediated by the promoted synthesis of palmitic acid in the Type II pneumocytes or by in-
754
Kauppila,
Puukka,
and Tuimala
creased activity of phosphatidic acid phosphohydrolase or other enzymes in Type II pneumocytes.” This is different from the route of action of glucocorticoids. IL is therefore of great importance that the beneficial influence exerted by glucocorticoids on fetal lung maturation should not be accompanied by suppression of PRL secretion and consequently of the PRL-mediated surfactant synthesis. In this study, short-term administration of dexamethasonc, with daily doses of 12, 8, and 4 mg. reduced serum estradiol by about SO%, as also reported previously.’ but despite this acute decrease the PRL level was maintained. However, a chronic depression of estradiol might result in a decreased basal secretion of maternal, and possibly of fetal PRL. Because PRL does not cross the placental barrier, the maternal PRL levels and their changes do not neressarily reflect PRL changes in the fetal compartment and consequently in the PRL-mediated biochemical events which effect fetal pulmonar) maturation. It is worth nothing that in nonpregnant states a daily dose of 0.5 to 2 mg of‘ dexatnethasone suppressed significantly basal PRL release.‘“+ I3 Short-term dexamethasone administration did not blunt the PRL and TSH response to 200 pg of int.ravenous TRH, and the response rate was of the same order as that recorded during normal late pregnancy. When nonpregnant women were subjected to TRH stimulation the PRL secretion was not altered by 2 mg of dexamethasone per day for S clays,‘” whereas 8 mg per day f’or 5 days blocked the secretion of both PRL and TSH,lfi and PRL response to insulin-induced hypoglycemia was lowered by even 1 mg of dexamethasane on the evening hefore the test.li The estrogen-induced increase in plasma PRL is possibly caused by a depletion of the PRL inhibitory factor (PIF).” It is thus reasonable to expect that the decreased level of estrogen induced by glucocorticoid administration may be followed bv a rise in PIF release and hence suppress PRL secretion. The present results suggest, however, that PRL during pregnancy is not particularly closely tied to estrogen level. Another mechanism whereby glucocorticoids may inhibit PRL secretion is at the hypothalamopituitar). level,” or alternatively the secretion may be inhibited by direct ac-
REFERENCES
I. Ehara, Y., Yen, S. S. C., and Siler, ‘r. M.: Serum prolactin levels during puberty, AM. J. OBSTET. GYNECOL. 121:995, 1975. 2. Vekemans, M., and Robyn, C.: InHuence of age on serum prolactin levels in women and men, Br. Med. J. 4~738, 1975. 3. L’Hermite, M., and Robyn, C.: Prolactin hypophysaird
MXAMETHASONE
7.
12
120
r1
i.m
4 mg
,i
,:
(
i
60
DAVS
DURING
AND
AFTER
THERAPY
Fig. 1. The relative mean levels (2S.E.M.) ot’ estradiol at 4:oo P.M. (blackcircles) and prolactin at 8:()0 A.M. and 4:oo P.M. (clear circles) during and after dexamethasone therapy in 1 ‘4 pregnant women.
Lion on the anterior pituitary cells.‘“, ‘7’l‘he suppressing effect of glucocorticoids on the release of differenr pituitary hormones depends on both t-he dose administered and the duration of administration. The doses ot dexamethasone used in this study are markedly higher than those recorded as inhibiting PRI. secretion in nonpregnant subjects. ‘5-‘.5 It seems. therefore, that during pregnancy other factors, possibly other hormones than estrogen, prevent the inhibitory action of glucocorticoids on PRL secretion. It is reported, for example, that progesterone is able to produce small increments in PRL secretion, when administered in vivo, by reducing hypothalamic PlF levels.” Progesterone levels, on the other hand, are not changed by corticosteroid administration.:, lx Clinically ir is important that the pharmacologic doses of dexamethasone in short-term therapy, as used in the prevention of RDS, do not produce any disturbances in maternal PRL formation and release. Peroral thyrotropin-releasing by courtesy of Hoffmann-La
hormone was c)btained Roche. Switzerland.
humaine: B&%tion radio-immunologique course de la grossesse, Ann. Endtxrinol.
et taux au (Paris) 33:357,
1972.
4. Wiedeman, E., Schwartz., E., and Frantz, A. G.: Acute and chronic estrogen effects upon serum somatomedin activity, growth hormone and prolactin in man. J, Clin. Endocrinol. Metab. 42:942. 1976. 5. Jacobi, J.. Lloyd, H. M., and Meares, J. r).: Onset ol
Volume Number
6.
7.
8.
9.
10.
11.
184 7
oestrogen-induced prolactin secretion and DNA synthesis by the rat pituitary gland, J. Endocrinol. 7235, 1977. Simmer, H. H., Tulchinsky, D., Gold, E., Frankland, M., Greipe, IM., and Gold, A. S.: On the regulation of estrogen production by cortisol and ACTH in human pregnancy at term, AM. J. OBSTET. GYNECOL. 119~283, 1974. Kauppila, A., Jouppila, P., Karvonen, P., Tuimala, R., and Ylikorkala, 0.: Effect of dexamethasone on blood levels of ACTH, cortisol, progesterone, estradiol and estrio1 during late pregnancy, lnt. J. Gynaecol. Obstet. 14: 177, 1976. Hammond, G. L., Viinikka, L., and Vihko, R.: Automation of radioimmunoassays for some sex steroids with use of both iodinated and tritiated ligands, Clin. Chem. 23: 1250, 1977. Liggins, G. C., and Howie, R. N.: A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants, Pediatrics 50:515, 1972. Farrell, P. M., and Zachman, R. D.: Induction of choline phosphotransferase and lecithin synthesis in fetal lung by corticosteroids, Science 179:297, 1973. Murphy, 13. E. P.: Cortisol: Its role in late pregnancy and labor, Contemp. Ob.-Gyn. 8:23, 1976.
Effect of dexamethasone
on PRL secretion
755
12. Hauth, J. C., Parker, C. R., MacDonald, P. C., Porter, 1. C.. and lohnston. I. M.: A role of fetal molactin in lung ~maturatio>, Obstet~~Gynecol. 51:81, 197’8. 13. Dussault, T. H.: The effect of dexamethasone on TSH and prolactin secretion after TRH stimulation. Can. Med. Assoc. J. Ill:1 195, 1974. 14. Cospinschi, G., L’Hermite, M., Laclerco, R., Golstein, J., Vanhaelst, L., Virasoro, E., and Robyn, C.: Effects of glucocorticoids on pituitary hormonal responses to hypoglycaemia. Inhibition of prolactin release, J. Clin. Endocrinol. Metab. 40:442, 1975. 15. @terman, P. O., Fagius, J., and Wide, L.: Prolactin levels in the insulin tolerance test with and without pretreatment with dexamethasone, Acta Endocrinol. 84:237, 1977. 16. Sowers, J. R., Carlson, H. E., Brautbar, N., and Hershman, J. M.: Effect of dexamethasone on profactin and TSH responses to TRH and Metoclorpramide in man, J. Clin. Endocrinol. Metab. 44:237, 1977. J. A.: Hypothalamic control of 17. Meites, J., and Clemens, urolactin secretion. Vitam. Horm. 30:165. 1972. 18. ?‘ulchinsky, D., and Okada, D. M.: Hormones in human pregnancy. IV. Plasma progesterone, AM. J. OBSTET. GYNECOL. 121:293, 1973.
KALJPPILA
MATTI
PUUKKA
RISTO
TUIMALA
Oulu, Finland It is established that PRL secretion is regulated by estrogens. Glucocorticokts, on the other hand, suppress estrogen secretion during pregnancy and may also inhibit PRL by direct hypothalamopituitary action. In this study PRL and estradiol were determined with specific radioimmunoassays in 14 women during gestational weeks 28 to 34 prior to, during, and following short-term intramuscular dexamethasone administration (12,8, and 4 mg on three consecutive days) used for prophylaxis of RDS in preterm infants. There were no s(gnificant alterations in PRL serum concentrations; estradiol showed a significant drop (P c 0.001) during all 3 days of treatment, returning to the pretreatment tevet on posttreatment day 1. The PRL and TSH responses to 200 pg of intravenous TRH on day 2 or 3 of dexamethasone treatment in six women during late pregnancy were not inhibited. Short-term dexamethasone treatment with pharmacologic doses does not suppress the physiologic secretion and release of PRL or the release induced by TRH during late pregnancy. (AM. J. OBSTET. GYNECOL. 1341752, 1979.)
IS MUCH evidence supporting the importance of estrogens in the physiologic regulation of prolactin (PRL) secretion in man. A parallel exists in the increase of estrogen and PRL secretion in girls at puberty’ and their decrease in aging women2 The increased circulating level of estrogens either during pregnancy3 or when induced by exogenous estrogen administration” is accompanied by a parallel rise in PRL secretion. In animal experiments the administration of estrogen resulted in increased mitotic activity of pituitary lactotropes in addition to the rise in PRL secretion,5 indicating that estrogens have an activating function directly on the pituitary cells secreting PRL. It is well known that exogenous glucocorticoids suppress the biosynthesis of estrogens63’ and consequently might modify PRL metabolism. Because short-term glucocorticoid therapy is widely used in the prevention of the respiratory distress syndrome (RDS) of preterm infants, this study aims to evaluate the influence of such THERE
From the De#wtment.s of G9necology and Obstetrics, Clinical Chemictry, University of Oulu. Receivedfor Accepted
publication September
June
6, 1978.
22, 1978.
Rejnint requests: Dr. Antti Kau@la, Obstettics and Gynecology, University Oulu, 90220 Outu 22, Finland.
752
and
Department of Central Hospital
of
therapy on either physiologic or thyrotropin-releasing hormone (TRH)-induced secretion of PRL. Paeflts
and -s
of patients. Twenty patients were treated with intramuscular dexamethasone for 3 days (12, 8, and 4 mg consecutively at 8:OOA.M.) in order to accelerate fetal pulmonary maturation. The ages of the patients ranged from 17 to 40 years (mean 27.5) and parity from I to 3 (mean 1.9). The threat of premature delivery was due to placenta previa in three cases and to premature uterine contractions in the other 17 cases. Two cases of mild pre-eclampsia, one of jaundice of pregnancy, and one of Rh incompatibility were diagnosed previously. The dexamethasone therapy was administered between gestational weeks 28 and 34 (mean 32.1) and all infants detivered between gestational weeks 34 to 42 (mean 37.4) were healthy. Perfonnaeice of the t&I, The basal secretion of PRL and estradiol was followed in 14 cases. Venous blood samples were drawn at 8:OO .&.M. and 4:OO P.M. from day 2 preceding dexamethasone treatment to day 2 after therapy. Estradiol was assayed only from afternoon samples; PRL was determined from both morning and afternoon specimens. The response of PRL and thyrotropin (TSH) t.o TRH was evaluated in six women who volunteered for Charactwization
0002-9378/79/150752+04$00.40/0
0
1979 The
(.. L. Mosby (.o
Volume Number
134 7
Effect
Table I. The mean (?S.E.M.) values of prolactin and thyrotropin prior administration of 200 pg of TRH in women treated with intramuscular control subjects during the third trimester of pregnancy Prolactin
Dexametharione
Healthy pregnant The
treated
Basal (N = 6)
controls (N = 9)
to and following dexamethasone
(pgIL) After
Patients
of dexarnethasone
20 min
209 + 24
450
210 + 10
429 2 28***
+- 39***
injection
Results Serum PRL and estradiol durhtg dexamethasone therapy. The mean (?S.E.M.) PRL level prior to dexamethasone administration (151 * 10 PgIL) did not differ significantly from the maximally changed level (133 -+ 11 pg’L) which was recorded on day 2 of ther-
secretion
(U/L) After
injection
60 min
Basal
20 min
60 min
287 _’ 22*
11.6 f 0.7 9.8 2 0.8
19.4 rf: 2.2*** 18.9 2 1.8***
17.0 2 2.1** 19.5 +- 1.9**
311 f 18*
753
the intravenous and in healthy pregnant
Thyrotropin
degrees of significance are calculated from the basal values: * = p < 0.05,
this study after receiving detailed information. After an overnight fast on the second (4 patients) or third (2 patients} day of dexamethasone treatment, an intravenous cannula was inserted at IO:00 A.M. The first blood sample was ‘drawn 30 minutes later, followed immediately by a bolus of 200 pg of TRH. The other specimens were taken 20 and 60 minutes after the TRH injection. Assays and evaluation of the results. The blood samples were centrifuged immediately and the serum was stored ;at -20” C. Estradiol was determined by means of a specific automated radioimmunoassay (RIA) which has recently been described in detail8 PRL and TSH were assayed with specific homologous RIA’s with CEA-IRE-SORIN kits (Department des Radioelements, 91190 Gis-sur-Yvette, France). All the samples were assayed in the same batch, and the within-assay variation was 7% for PRL and 8% for TSH. The reference PRL was standardized against the research Standard A for human PRL, 711222, obtained from the division of Biological Standards, National Institute for Medical Research, London; 40 IU of this standard were found to be equivalent to 1 ng of immunochemical human PRL, Friesen No. 1, which was supplied by the NIAMDD. The TSH reference preparation was First IRP MRC 68/38. All determinations were made in duplicate. The results are given as both absolute and relative values, the latter being calculated from the mean level prior to the dexamethasone treatment and in the TRH test from the intial level, according to the formula .. value - mtttal value x loo. initial value
on PRL
** = p < 0.01, *** = p < O.OOI.
apy at 4:00 P.M.-a decrease of 12.5% (Fig. 1). Relative estradiol values, on the other hand, were significantly lowered on all 3 days of therapy (p < 0.001). The mean basal level of estradiol was 19.8 * 3.3 pg/L, and the lowest value obtained (12.0 + 2.7 PgIL) was on day 2 of therapy. The return to initial levels was recorded on day 1 after therapy. PRL and TSH responses to TRH. The circulating levels of both PRL and TSH increased after TRH injection in each of the six women tested during dexamethasone treatment as well as in nine healthy control subjects examined during the last trimester of pregnancy (Table I). The significant rise in PRL level in the dexamethasone group at 20 and 60 minutes did not differ from the corresponding results In the control subjects. The significant changes in the level of TSH in the dexamethasone group at 20 and 60 minutes were similar to those in the control subjects.
Comment Antepartum glucocorticoid therapy for the prevention of RDS in preterm infants has been widely accepted since Liggins and Howies in 1972 proved it to be beneficial in a controlled clinical trial. The effect of glucocorticoids is probably mediated by the induction of phosphocholine transferase.‘O Because the increase in the endogenous fetal cortisol is not a necessary antecedent of augmented surfactant synthesis,“, ” and because the reduction of RDS is found only in infants ivhose mothers were treated during a certain gestational period, there seems reason to conclude that glucocorticoids have only a permissive role in fetal lung maturation. Recently it has been reported that the incidence of RDS among infants whose cord plasma level of PRL is less than 200 rig/ml was significantly higher than among those with PRL concentration higher than 200 rig/ml.‘* It has been suggested that an augmented surfactant formation, lung maturation, and increased PRL level are causally related. The effect of PRL is believed to be mediated by the promoted synthesis of palmitic acid in the Type II pneumocytes or by in-
754
Kauppila,
Puukka,
and Tuimala
creased activity of phosphatidic acid phosphohydrolase or other enzymes in Type II pneumocytes.” This is different from the route of action of glucocorticoids. IL is therefore of great importance that the beneficial influence exerted by glucocorticoids on fetal lung maturation should not be accompanied by suppression of PRL secretion and consequently of the PRL-mediated surfactant synthesis. In this study, short-term administration of dexamethasonc, with daily doses of 12, 8, and 4 mg. reduced serum estradiol by about SO%, as also reported previously.’ but despite this acute decrease the PRL level was maintained. However, a chronic depression of estradiol might result in a decreased basal secretion of maternal, and possibly of fetal PRL. Because PRL does not cross the placental barrier, the maternal PRL levels and their changes do not neressarily reflect PRL changes in the fetal compartment and consequently in the PRL-mediated biochemical events which effect fetal pulmonar) maturation. It is worth nothing that in nonpregnant states a daily dose of 0.5 to 2 mg of‘ dexatnethasone suppressed significantly basal PRL release.‘“+ I3 Short-term dexamethasone administration did not blunt the PRL and TSH response to 200 pg of int.ravenous TRH, and the response rate was of the same order as that recorded during normal late pregnancy. When nonpregnant women were subjected to TRH stimulation the PRL secretion was not altered by 2 mg of dexamethasone per day for S clays,‘” whereas 8 mg per day f’or 5 days blocked the secretion of both PRL and TSH,lfi and PRL response to insulin-induced hypoglycemia was lowered by even 1 mg of dexamethasane on the evening hefore the test.li The estrogen-induced increase in plasma PRL is possibly caused by a depletion of the PRL inhibitory factor (PIF).” It is thus reasonable to expect that the decreased level of estrogen induced by glucocorticoid administration may be followed bv a rise in PIF release and hence suppress PRL secretion. The present results suggest, however, that PRL during pregnancy is not particularly closely tied to estrogen level. Another mechanism whereby glucocorticoids may inhibit PRL secretion is at the hypothalamopituitar). level,” or alternatively the secretion may be inhibited by direct ac-
REFERENCES
I. Ehara, Y., Yen, S. S. C., and Siler, ‘r. M.: Serum prolactin levels during puberty, AM. J. OBSTET. GYNECOL. 121:995, 1975. 2. Vekemans, M., and Robyn, C.: InHuence of age on serum prolactin levels in women and men, Br. Med. J. 4~738, 1975. 3. L’Hermite, M., and Robyn, C.: Prolactin hypophysaird
MXAMETHASONE
7.
12
120
r1
i.m
4 mg
,i
,:
(
i
60
DAVS
DURING
AND
AFTER
THERAPY
Fig. 1. The relative mean levels (2S.E.M.) ot’ estradiol at 4:oo P.M. (blackcircles) and prolactin at 8:()0 A.M. and 4:oo P.M. (clear circles) during and after dexamethasone therapy in 1 ‘4 pregnant women.
Lion on the anterior pituitary cells.‘“, ‘7’l‘he suppressing effect of glucocorticoids on the release of differenr pituitary hormones depends on both t-he dose administered and the duration of administration. The doses ot dexamethasone used in this study are markedly higher than those recorded as inhibiting PRI. secretion in nonpregnant subjects. ‘5-‘.5 It seems. therefore, that during pregnancy other factors, possibly other hormones than estrogen, prevent the inhibitory action of glucocorticoids on PRL secretion. It is reported, for example, that progesterone is able to produce small increments in PRL secretion, when administered in vivo, by reducing hypothalamic PlF levels.” Progesterone levels, on the other hand, are not changed by corticosteroid administration.:, lx Clinically ir is important that the pharmacologic doses of dexamethasone in short-term therapy, as used in the prevention of RDS, do not produce any disturbances in maternal PRL formation and release. Peroral thyrotropin-releasing by courtesy of Hoffmann-La
hormone was c)btained Roche. Switzerland.
humaine: B&%tion radio-immunologique course de la grossesse, Ann. Endtxrinol.
et taux au (Paris) 33:357,
1972.
4. Wiedeman, E., Schwartz., E., and Frantz, A. G.: Acute and chronic estrogen effects upon serum somatomedin activity, growth hormone and prolactin in man. J, Clin. Endocrinol. Metab. 42:942. 1976. 5. Jacobi, J.. Lloyd, H. M., and Meares, J. r).: Onset ol
Volume Number
6.
7.
8.
9.
10.
11.
184 7
oestrogen-induced prolactin secretion and DNA synthesis by the rat pituitary gland, J. Endocrinol. 7235, 1977. Simmer, H. H., Tulchinsky, D., Gold, E., Frankland, M., Greipe, IM., and Gold, A. S.: On the regulation of estrogen production by cortisol and ACTH in human pregnancy at term, AM. J. OBSTET. GYNECOL. 119~283, 1974. Kauppila, A., Jouppila, P., Karvonen, P., Tuimala, R., and Ylikorkala, 0.: Effect of dexamethasone on blood levels of ACTH, cortisol, progesterone, estradiol and estrio1 during late pregnancy, lnt. J. Gynaecol. Obstet. 14: 177, 1976. Hammond, G. L., Viinikka, L., and Vihko, R.: Automation of radioimmunoassays for some sex steroids with use of both iodinated and tritiated ligands, Clin. Chem. 23: 1250, 1977. Liggins, G. C., and Howie, R. N.: A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants, Pediatrics 50:515, 1972. Farrell, P. M., and Zachman, R. D.: Induction of choline phosphotransferase and lecithin synthesis in fetal lung by corticosteroids, Science 179:297, 1973. Murphy, 13. E. P.: Cortisol: Its role in late pregnancy and labor, Contemp. Ob.-Gyn. 8:23, 1976.
Effect of dexamethasone
on PRL secretion
755
12. Hauth, J. C., Parker, C. R., MacDonald, P. C., Porter, 1. C.. and lohnston. I. M.: A role of fetal molactin in lung ~maturatio>, Obstet~~Gynecol. 51:81, 197’8. 13. Dussault, T. H.: The effect of dexamethasone on TSH and prolactin secretion after TRH stimulation. Can. Med. Assoc. J. Ill:1 195, 1974. 14. Cospinschi, G., L’Hermite, M., Laclerco, R., Golstein, J., Vanhaelst, L., Virasoro, E., and Robyn, C.: Effects of glucocorticoids on pituitary hormonal responses to hypoglycaemia. Inhibition of prolactin release, J. Clin. Endocrinol. Metab. 40:442, 1975. 15. @terman, P. O., Fagius, J., and Wide, L.: Prolactin levels in the insulin tolerance test with and without pretreatment with dexamethasone, Acta Endocrinol. 84:237, 1977. 16. Sowers, J. R., Carlson, H. E., Brautbar, N., and Hershman, J. M.: Effect of dexamethasone on profactin and TSH responses to TRH and Metoclorpramide in man, J. Clin. Endocrinol. Metab. 44:237, 1977. J. A.: Hypothalamic control of 17. Meites, J., and Clemens, urolactin secretion. Vitam. Horm. 30:165. 1972. 18. ?‘ulchinsky, D., and Okada, D. M.: Hormones in human pregnancy. IV. Plasma progesterone, AM. J. OBSTET. GYNECOL. 121:293, 1973.
