\g=a\-MSH, ACTH and \g=b\-endorphin were measured by radioimmunoassay in samples of amniotic fluid collected from the 32nd to the 38th gestational week and at labour from normal pregnancies and pregnancies complicated by gestosis. In normal pregnancies, the concentration of \g=a\-MSH, ACTH and \g=b\-endorphin remained relatively constant during the last 7 gestational weeks, but increased at labour above the values of the 38th week by 88, 143 and 96%, respectively. A positive correlation between \g=b\-endorphin and \g=a\-MSH (r=0.92) or ACTH (r=0.76) levels was found when labour values were considered in the regression analysis. In contrast, when labour values were excluded, only a poor positive correlation between \g=b\-endorphin and \g=a\-MSH (r=0.52) was found. In complicated pregnancies, \g=a\-MSH and ACTH concentrations were similar to those found in normal pregnancies; on the other hand, the level of \g=b\-endorphin, was found to be 130% higher than normal. As in normal pregnancies, \g=a\-MSH, ACTH and \g=b\-endorphin levels increased at labour, but only by 46, 44 and 23%, respectively. In contrast to in normal pregnancies, the correlation between \g=b\-endorphin and \g=a\-MSH or ACTH was not significantly modified by labour values. The present results confirm and extend previous studies showing that \g=b\-endorphinmay be considered a marker of fetal distress and that the fetal pituitary is capable of reacting to stressful stimuli in normal and suffering fetuses.The major pro-opiomelanocorticotropin (POMC) derivatives a-MSH, ACTH and ß-endorphin (1,2) appear at very early stages of fetal development (3,4) and are found not only in the fetal pituitary gland but also in fetal plasma and amniotic fluid (5,6). The fetal pituitary gland seems to be the major source of these peptides in fetal fluids (7,8), although they have been detected also in placenta and amniochorial membranes (9,10). It has also been shown that amniotic a-MSH and ß-endorphin decrease during pregnancy, the highest levels being found in the 1st trimester and the lowest in the 3rd trimester, whereas the ACTH concentra¬ tion was found to be lowest in the 2nd and highest in the 3rd trimester (6). Moreover a-MSH seems to play an important role in the development of the feto-placental unit (11,12) and, like ACTH, in the control of fetal steroidogenesis (13,14). Neverthe¬ less, very little is known about their physiological function in prenatal life. While it is well established that in adult life these peptides are released by stressful stimuli to coordinate biochemical, endocrinological and behavioural changes that consti¬ tute an adaptative mechanism against stress (15), few and incomplete results exist about the effect of stress on fetal plasma and amniotic concentration of POMC-derived peptides in normal pregnancies or pregnancies complicated by maternal disorders that can be associated with fetal discomfort. The only exception is for amniotic ß-endorphin, whose concentration was found to be increased in suf¬ fering fetuses (8,16,17).With the a...

The influence of gamma-amino-beta-hydroxy butyric acid (GABOB) treatment on pituitary function has been investigated in this study. Different doses (50 x 100 mg) of GABOB were iv injected into three and six normal women, respectively. PRL and GH plasma levels were measured before and after the injection. The treatment with 150 mg GABOB, performed in another two normal women, was interrupted because of side-effects (loss of consciousness etc.) due to the treatment. The treatment with 50 mg GABOB did not induce significant variations of the two hormones; however, significant increases of PRL (P less than 0.05) and GH (P less than 0.01) plasma levels were observed after injection with 100 mg GABOB. The present data suggest that gamma-amino butyric acid (GABA) itself of GABAergic drugs might play an important role in the control of hypothalamic-pituitary function.

Immunoreactive alpha-melanocyte stimulating hormone (IR-alpha-MSH)-like activity was measured by radioimmunoassay (RIA) in at term pregnancy amniotic fluid prior and after adsorption on a Sep-pak C18 cartridge. alpha-MSH activity was 3-4 times lower after Sep-pak purification but, unlike the levels of IR-alpha-MSH in the fluid analyzed in toto, increased linearly with the volume of fluid analyzed. Furthermore, fractionation by high pressure liquid chromatography (HPLC) revealed that IR-alpha-MSH recovered from the Sep-pak was due to several peptides rather than to a single peptide. The most abundant of them (50% of total activity) behaved like authentic des-acetyl-alpha-MSH. Since des-acetyl-alpha-MSH is also the most abundant alpha-MSH-like peptide in the fetal pituitary gland, the present results suggest that the fetal pituitary is a main source of des-acetyl-alpha-MSH in the amniotic fluid.

Prenatal diagnosis with globin chain synthesis analysis on fetal red blood cells concentrated by NH4Cl-NH4HCO3 differential lysis of maternal cells (Orskov lysis) was carried out in 27 pregnancies at risk for beta thalassaemia and one at risk for sickle cell beta0 thalassaemia. The beta/gamma globin chain synthesis ratio was also determined after anti-i-differential agglutination (12 cases), in almost pure fetal samples (sic cases) and by extrapolation (one case). Differential lysis permitted the study of samples drawn by placental aspiration containing as little as 3.2% fetal red blood cells. There was no consistent difference between the beta/gamma ratios observed after differentail lysis and those determined after the use of the other approaches. A presumptive diagnosis of homozygous beta thalassaemia was made in nine cases. All but one of these pregnancies was terminated. The absence of beta chain synthesis was confirmed by the study of fetal blood after abortion in four cases with suitable samples. Of the remaining pregnancies, six proceeded to term and non-homozygous infants were delivered. The others are still in progress. No fetal loss occurred. Orskov lysis seems to be a very reliable method for prenatal diagnosis of beta chain abnormalities. Moreover it can minimize the number and duration of placental aspirations required and thus the risk to the fetus.

SUMMARYThe results of 200 antenatal diagnoses in pregnancies at risk for homozygous r-thalassaemia, carried out on fetal blood samples obtained by placental aspiration in the second trimester, are described. Globin chain synthesis in the fetuses was measured by means of 3H-leucine incorporation and separation of the chains on carboxy-methyl-cellulose columns. Fetal red cell enrichment was performed by NH4Cl-N`H4HCO3 differential lysis of maternal cells or anti-i differential agglutination. Sufficient fetal blood for analysis was obtained in 97.5 % of the cases. The overall fetal loss rate was 6.5 %, but it declined from 10% in the first consecutive 100 cases to 3 % in the last 100 cases. Fetal loss was the result of early or late intrauterine death or spontaneous abortion. Forty-two homozygous fetuses had no 3-chain synthesis and one had a very low 3/ry ratio (0.005). Of the pregnancies, 37 were terminated at parental request and four aborted spontaneously. Absence of 5-chain radioactivity was confirmed in 12 abortuses with suitable cord blood samples for analysis. Two pregnancies with homozygous fetuses were not terminated, as one member of each couple was a devout Catholic. As expected, both infants developed Cooley's anaemia. Follow-up of the 146 infants, diagnosed in utero as non-homozygotes, showed cerebral palsy in one and a small cutaneous needle injury in three. None of these developed homozygous P-thalassaemia. Even P-thalassaemia trait with a F3/y ratio of 0.046 i 0-012 can be distinguished from normal, showing a r3/y ratio of 0-086 ± 0.019 with a high degree of certainty.