Thyrotropin releasing hormone does not stimulate prolactin release in the preterm human fetus
Elio
Roti, Eliana Gardini, Roberta Minelli, Lina Bianconi, Alessandro Alboni and Lewis E. Braverman
Centro per lo Studio, Prevenzione, Diagnosi e Cura delle Tireopatie1, Cattedra di Endocrinología e Patología Costituzionale, University of Parma Medical School, Parma; Divisione di Ostetricia e Ginecología2, Ospedale C. Magati, Scandiano, Italy, and the Division of Endocrinology and Metabolism3, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Abstract.
Previous studies have suggested that fetal PRL secretion does not respond to stimuli such as TRH, metoclopramide, and cimetidine. It was postulated that the lack of response to TRH could be due to the possibility that, in the term fetus, lactotropes secrete PRL maximally and would be unresponsive to further stimulation. In order to study this hypothesis, 200 \g=m\gTRH or saline were administered to preterm pregnant women in labor. Maternal blood was obtained before TRH and saline administration. Maternal and cord blood were obtained at parturition. PRL, TSH, T4 and T3 concentrations were measured in all sera. TRH administration induced a significant increase in maternal serum PRL, TSH and T3 concentrations. In the cord blood of newborns whose mothers received TRH, serum TSH, T4 and T3 concentrations were significantly higher than in cord blood of newborns whose mothers received saline. Cord blood serum PRL concentrations were unchanged after TRH administration. This latter finding suggests that fetal lactotropes do not respond to TRH in the preterm fetus. Desensitization of fetal PRL secreting cells to TRH stimulation and/or the inhibitory effect of elevated fetal circulating corticosteroids on TRH-induced PRL secretion may explain the absent PRL response to TRH during fetal life.
During human fetal life, pituitary prolactin secre¬ tion is present by the end of the first trimester of pregnancy. Thereafter, pituitary and serum PRL concentrations increase progressively, reaching the highest levels at full term (1). The mechanisms reg¬ ulating PRL secretion have been thoroughly inves¬ tigated in animals (1). In the term human fetus it
has been observed that serum PRL concentrations increased by the administration of TRH
were not
(2,3), metoclopramide (4,5), a potent dopamine an¬ tagonist and cimetidine, an H, receptor antagonist (6), whereas serum PRL was decreased by bromo-
criptine
administration (7). Since TRH administration to the mother did not increase serum PRL concentrations in the term fetus, we suggested that pituitary PRL secretion was maximal in the term fetus and was, therefore, unresponsive to further stimulation (3). To further evaluate this hypothesis, we have now studied the PRL response to TRH in preterm human fetuses since pituitary and serum PRL concentrations are not as yet at peak concentrations.
Subjects and Methods obtained, 39 women with The majority of these studied. preterm pregnancies women had premature rupture of the membranes. TRH, 200 ng (Biodata, Milan, Italy) were rapidly injected iv to 20 randomly selected women during premature labor, 4 of whom underwent delivery by Caesarian section. Nine¬ After informed
consent was were
of saline (control) delivered by Caesarian section. Patients were assigned to each group in random order. TRH or saline were given before the administra¬ tion of the anesthetic agents atropine, thiopental, and curare, which do not affect the PRL response to TRH. teen women
received
an
during labor, 3 of whom
injection
were
The times of injection and of cord and maternal blood collections at parturition were recorded. The intervals of time between TRH and saline injection and cord blood collection were 59.7 ± 7.9 (mean ± sem) and 65.8 ± 9.0 min, respectively. The ages of mothers receiving TRH and saline were 26.1 ± 0.8 and 26.4 ±1.2 years, respectively. The gestational ages of the TRH- and saline-treated groups were 35.7 ± 0.4 (range 31-37) and 35.6 ± 0.3 (range 32-37) weeks, respectively. The birth weight and apgar score of the neonates whose mothers received TRH and saline were 2642 ± 92 g and 9.2 ± 0.1 and 2672 ± 94 g and 9.1 ± 0.1, respectively. Maternal blood specimens were obtained before TRH or saline ad¬ ministration and at parturition. At birth, cord blood was obtained from all the neonates. Serum was rapidly sepa¬ rated and frozen at 20°C until analyzed. PRL, TSH, T4, and T3 were measured in all samples by radioimmunoassays. All serum samples were diluted 1:11 in buffer for PRL determinations. All samples were as¬ sayed for each hormone in duplicate, in the same assay and in random order. Intra-assay coefficients of variation were: 3.9% for PRL; 6.3% for T4; 5.6% for T3, and 7.9% for TSH. No adverse effects were observed in women and neo¬ nates receiving TRH during labor, delivery, and the postpartum period. The clinical course of neonates whose mothers received TRH was uneventful. A regional neo¬ natal thyroid screening program based upon T4 and TSH determinations in blood collected on filter paper on day 4 revealed no thyroid abnormalities. Unpaired Student's t-test was employed to compare maternal hormone values before treatment between the two groups. Maternal hormone values at parturition be¬ tween TRH- and saline-treated groups were compared by a multifactor analysis of variance (covariance). Fetal hor¬ mone values of neonates whose mothers received TRH or saline were compared by a covariance analysis, which takes into account as covariates the gestational age and the —
Table 1. Serum concentrations of PRL, TSH, TRH.
T4 and T3 in pregnant
interval of time elapsed between saline or TRH injection and cord blood sampling. The statistical analyses have been conducted with the aid of a CDC 7300 computer following the procedures reported in the SAS manual (SAS Institute, Inc, Cary, NC). All results are expressed as mean
±
sem.
Results Maternal serum hormone concentrations Maternal serum hormone values just prior to and after TRH or saline administration are reported (Table 1 ) No significant differences in basal serum PRL, TSH, T4 and T3 concentrations were ob¬ served between TRH- and saline-treated mothers (unpaired Student's t-test). At parturition, serum PRL concentrations in¬ creased significantly (p
Elio
Roti, Eliana Gardini, Roberta Minelli, Lina Bianconi, Alessandro Alboni and Lewis E. Braverman
Centro per lo Studio, Prevenzione, Diagnosi e Cura delle Tireopatie1, Cattedra di Endocrinología e Patología Costituzionale, University of Parma Medical School, Parma; Divisione di Ostetricia e Ginecología2, Ospedale C. Magati, Scandiano, Italy, and the Division of Endocrinology and Metabolism3, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Abstract.
Previous studies have suggested that fetal PRL secretion does not respond to stimuli such as TRH, metoclopramide, and cimetidine. It was postulated that the lack of response to TRH could be due to the possibility that, in the term fetus, lactotropes secrete PRL maximally and would be unresponsive to further stimulation. In order to study this hypothesis, 200 \g=m\gTRH or saline were administered to preterm pregnant women in labor. Maternal blood was obtained before TRH and saline administration. Maternal and cord blood were obtained at parturition. PRL, TSH, T4 and T3 concentrations were measured in all sera. TRH administration induced a significant increase in maternal serum PRL, TSH and T3 concentrations. In the cord blood of newborns whose mothers received TRH, serum TSH, T4 and T3 concentrations were significantly higher than in cord blood of newborns whose mothers received saline. Cord blood serum PRL concentrations were unchanged after TRH administration. This latter finding suggests that fetal lactotropes do not respond to TRH in the preterm fetus. Desensitization of fetal PRL secreting cells to TRH stimulation and/or the inhibitory effect of elevated fetal circulating corticosteroids on TRH-induced PRL secretion may explain the absent PRL response to TRH during fetal life.
During human fetal life, pituitary prolactin secre¬ tion is present by the end of the first trimester of pregnancy. Thereafter, pituitary and serum PRL concentrations increase progressively, reaching the highest levels at full term (1). The mechanisms reg¬ ulating PRL secretion have been thoroughly inves¬ tigated in animals (1). In the term human fetus it
has been observed that serum PRL concentrations increased by the administration of TRH
were not
(2,3), metoclopramide (4,5), a potent dopamine an¬ tagonist and cimetidine, an H, receptor antagonist (6), whereas serum PRL was decreased by bromo-
criptine
administration (7). Since TRH administration to the mother did not increase serum PRL concentrations in the term fetus, we suggested that pituitary PRL secretion was maximal in the term fetus and was, therefore, unresponsive to further stimulation (3). To further evaluate this hypothesis, we have now studied the PRL response to TRH in preterm human fetuses since pituitary and serum PRL concentrations are not as yet at peak concentrations.
Subjects and Methods obtained, 39 women with The majority of these studied. preterm pregnancies women had premature rupture of the membranes. TRH, 200 ng (Biodata, Milan, Italy) were rapidly injected iv to 20 randomly selected women during premature labor, 4 of whom underwent delivery by Caesarian section. Nine¬ After informed
consent was were
of saline (control) delivered by Caesarian section. Patients were assigned to each group in random order. TRH or saline were given before the administra¬ tion of the anesthetic agents atropine, thiopental, and curare, which do not affect the PRL response to TRH. teen women
received
an
during labor, 3 of whom
injection
were
The times of injection and of cord and maternal blood collections at parturition were recorded. The intervals of time between TRH and saline injection and cord blood collection were 59.7 ± 7.9 (mean ± sem) and 65.8 ± 9.0 min, respectively. The ages of mothers receiving TRH and saline were 26.1 ± 0.8 and 26.4 ±1.2 years, respectively. The gestational ages of the TRH- and saline-treated groups were 35.7 ± 0.4 (range 31-37) and 35.6 ± 0.3 (range 32-37) weeks, respectively. The birth weight and apgar score of the neonates whose mothers received TRH and saline were 2642 ± 92 g and 9.2 ± 0.1 and 2672 ± 94 g and 9.1 ± 0.1, respectively. Maternal blood specimens were obtained before TRH or saline ad¬ ministration and at parturition. At birth, cord blood was obtained from all the neonates. Serum was rapidly sepa¬ rated and frozen at 20°C until analyzed. PRL, TSH, T4, and T3 were measured in all samples by radioimmunoassays. All serum samples were diluted 1:11 in buffer for PRL determinations. All samples were as¬ sayed for each hormone in duplicate, in the same assay and in random order. Intra-assay coefficients of variation were: 3.9% for PRL; 6.3% for T4; 5.6% for T3, and 7.9% for TSH. No adverse effects were observed in women and neo¬ nates receiving TRH during labor, delivery, and the postpartum period. The clinical course of neonates whose mothers received TRH was uneventful. A regional neo¬ natal thyroid screening program based upon T4 and TSH determinations in blood collected on filter paper on day 4 revealed no thyroid abnormalities. Unpaired Student's t-test was employed to compare maternal hormone values before treatment between the two groups. Maternal hormone values at parturition be¬ tween TRH- and saline-treated groups were compared by a multifactor analysis of variance (covariance). Fetal hor¬ mone values of neonates whose mothers received TRH or saline were compared by a covariance analysis, which takes into account as covariates the gestational age and the —
Table 1. Serum concentrations of PRL, TSH, TRH.
T4 and T3 in pregnant
interval of time elapsed between saline or TRH injection and cord blood sampling. The statistical analyses have been conducted with the aid of a CDC 7300 computer following the procedures reported in the SAS manual (SAS Institute, Inc, Cary, NC). All results are expressed as mean
±
sem.
Results Maternal serum hormone concentrations Maternal serum hormone values just prior to and after TRH or saline administration are reported (Table 1 ) No significant differences in basal serum PRL, TSH, T4 and T3 concentrations were ob¬ served between TRH- and saline-treated mothers (unpaired Student's t-test). At parturition, serum PRL concentrations in¬ creased significantly (p
