Placental growth hormone and IGF-I in a pregnant woman with Pit-1 deficiency

The respective contributions of pituitary and placental GH to circulating IGF-I in pregnant women have not been well established. We measured the serum concentrations of placental growth hormone (PGH) and IGF-I in a woman with pit-1 deficiency before, during and after pregnancy, resulting in the birth of a healthy child (not pit-1 deficient). Both PGH and IGF-I concentrations were below the assay detection limit before and after pregnancy. During pregnancy, PGH and IGF-I levels increased steadily; the concentrations of PGH and IGF-I in late pregnancy were comparable with levels previously measured in normal pregnancies. PGH and IGF-I concentrations were strongly correlated throughout pregnancy (r = 0.90; P = 0.002). PGH was undetectable in cord serum, whilst the IGF-I concentration was within the normal range. The findings of this case study corroborate the notion that PGH is the prime regulator of maternal serum IGF-I during pregnancy.     

Maternal-fetal transfer of melatonin in pregnant women near term

Abstract: Our objective was to evaluate the maternal-fetal transfer of melatonin in pregnant women. Serum melatonin concentration was measured by high-performance liquid chromatography with electrochemical detection in a maternal vein and in the umbilical artery and umbilical vein at the time of birth. Blood samples were obtained from 12 women who had spontaneously delivered vaginally at night. A single oral dose of melatonin was administered to each of 33 patients who underwent a cesarean section, and. blood samples were taken at 1,2, 3, or 4 hr after the administration of melatonin at delivery. Cesarean section was performed between 1300 and 1500 hr. The mean melatonin concentrations of melatonin in maternal peripheral venous blood and umbilical arterial and umbilical venous blood did not differ significantly, and positive correlations in the serum levels of melatonin were observed between the three sources of blood. The oral administration of 3 mg of melatonin to pregnant women led to marked increases in the serum levels of melatonin, with maximum levels observed 2 hr (21.84 ± 2.09 ng/ml) after drug administration. Changes in serum levels of melatonin in the umbilical vein and artery resembled those found in the maternal vein. Serum melatonin concentrations did not differ significantly between the maternal vein and the umbilical veins. Serum levels of melatonin in the umbilical vein after the administration of melatonin were significantly and closely correlated with those in the maternal vein (r = 0.924, ( P < 0.001). These results suggest that, in humans, melatonin is transferred from the maternal to the fetal circulation both easily and rapidly. A potential for the therapeutic use of melatonin as an antioxidant exists in the patients with preeclampsia.     

Predicting the response of growth hormone-deficient children to long term treatment with human growth hormone.

A previous study showed that when GH-deficient children below the third percentile in height are treated with 0.168 U human GH (hGH)/kg BW3/4 for 10 days, their height increases by 0.3--1.9 cm during the next 8 weeks. The present study determined whether this acute response would predict the child's long term response to 1 yr of treatment with the same dose of hGH given three times a week. Eighteen GH-deficient children and adolescents, aged 8--16 yr, were measured every 2 weeks over 108 weeks. After a control period of 12 weeks (period 1), the patient received hGH for 10 days. During the remainder of the 12 weeks of period 2 and during the next 12 weeks (period 3), hGH was not given. Patients recieved hGH three times a week during periods 4 and 5 (24 weeks each). Periods 6 and 7 (12 weeks each) were posttreatment control periods. During periods 1, 3, 6, and 7, rate of growth was less than 0.2 cm/month. During period 2, the rate ranged between 0.1--0.8 cm/month. During periods 4 and 5, the growth rate ranged from 0.2--1.0 cm/month. Rate of growth during periods 4 and 5 (y) was related to rate during period 2 (x) by the equation y = 0.027 + 1.17 x. The correlation coefficient between y and x was 0.91 (P less than 0.001). The increment in height which will occur during 48 weeks of treatment can be predicted from the response to 10 days of treatment by this equation. The SE of the prediction averages +/- 1.2 cm/yr.     

Pelvic circulation in the pregnant woman

The authors point out the fact that there are few publications on this subject. Besides variations related to functional and hormonal associated with pregnancy, temporary variations occur in the venous system and which take the form of the development of extra-intra pelvic anastomoses at several sites.     

Gastrointestinal endoscopy in the pregnant woman

About 20000 gastrointestinal endoscopies are performed annually in America in pregnant women. Gastrointestinal endoscopy during pregnancy raises the critical issue of fetal safety in addition to patient safety. Endoscopic medications may be potentially abortifacient or teratogenic. Generally, Food and Drug Administration category B or C drugs should be used for endoscopy. Esophagogastroduodenoscopy(EGD) seems to be relatively safe for both mother and fetus based on two retrospective studies of 83 and 60 pregnant patients. The diagnostic yield is about 95% when EGD is performed for gastrointestinal bleeding. EGD indications during pregnancy include acute gastrointestinal bleeding, dysphagia 1 wk, or endoscopic therapy. Therapeutic EGD is experimental due to scant data, but should be strongly considered for urgent indications such as active bleeding. One study of 48 sigmoidoscopies performed during pregnancy showed relatively favorable fetal outcomes, rare bad fetal outcomes, and bad outcomes linked to very sick mothers. Sigmoidoscopy should be strongly considered for strong indications,including significant acute lower gastrointestinal bleeding, chronic diarrhea, distal colonic stricture, suspected inflammatory bowel disease flare, and potential colonic malignancy. Data on colonoscopy during pregnancy are limited. One study of 20 pregnant patients showed rare poor fetal outcomes. Colonoscopy is generally experimental during pregnancy, but can be considered for strong indications: known colonic mass/stricture, active lower gastrointestinal bleeding, or colonoscopic therapy. Endoscopic retrograde cholangiopancreatography(ERCP) entails fetal risks from fetal radiation exposure. ERCP risks to mother and fetus appear to be acceptable when performed for ERCP therapy, as demonstrated by analysis of nearly 350 cases during pregnancy. Justifiable indications include symptomatic or complicated choledocholithiasis, manifested by jaundice, cholangitis, gallstone pancreatitis, or dilated choledochus. ERCP should be performed by an expert endoscopist, with informed consent about fetal radiation risks, minimizing fetal radiation exposure, and using an attending anesthesiologist. Endoscopy is likely most safe during the second trimester of pregnancy.     

Danger of iodine drugs in the pregnant woman

The authors draw attention to the fact that the possible effects of drugs containing iodine are often neglected during pregnancy. As an example, they report the following observation : "A young woman with benign asthma, treated for 14 years Asthmasedine and Asthmaligne, gave birth, on the 36th week of pregnancy, to a child apparenty dead but who was able to be reanimated. The child showed two types of signs : respiratory distress due to higher neurological disorders and a multinodular, non-compressing goiter. These two complications were caused by a congenital hypothyroidism corroborated by laboratory tests and due to the prolonged absorption of iodinated drugs by the mother". In conclusion, in cases of women receiving during pregnancy high doses of drugs containing iodine (250 such drugs are recorded in the Vidal), it is desirable to control the effect on the fetus and to propose an intra-amniotic therapy with L-Thyroxine, thus allowing a cerebral development close to normal.     

Liver retinoids and retinol esterification in fetal and pregnant rats at term

Retinol esterification in fetal rats and their mothers at term was studied in liver microsomes. The esterification rate was 0.28 +/- 0.05 nmol ester formed per milligram protein per minute, a value somewhat lower than that found in their mothers (0.44 +/- 0.11). The fetuses had significant amounts of liver retinoids. Analysis by high-performance liquid chromatography showed that the retinoid store consisted mainly of retinyl ester both in fetal and adult rat livers, but the fetal livers had higher percentages of free retinol and retinyl oleate than the adult livers. The presence of retinol esterification and a retinyl ester store in fetal rat liver at term is in accordance with the view that retinol brought to liver on retinol-binding protein can be taken up and retained there.     

Parathyroid hormone increases epidermal growth factor receptors in cultured human trophoblastic cells from early and term placenta

The effect of PTH on the epidermal growth factor (EGF) receptor was analyzed during the in vitro differentiation of human cytotrophoblasts. The cytotrophoblasts were isolated by a trypsin-DNase method from first trimester and term placentas and purified on a Percoll gradient. In culture, these cells aggregated and fused together to form a syncytium. This in vitro differentiation was associated with a 2-fold increase in 125I-EGF binding after 48 h of culture. The addition of 0.1 microM PTH (PTH-treated cells) to the culture medium induced a significant 2- to 3-fold increase (P less than 0.005) in EGF binding. The effect was dose related with a maximum obtained at a 1 nM concentration. Scatchard analyses revealed that PTH-treated cells possess a 2-fold higher number of high affinity sites as compared to control cells from early placenta (0.71 +/- 0.06 pmol/mg protein and 0.34 +/- 0.04 pmol/mg protein, respectively) and from term placenta (1.24 +/- 0.10 pmol/mg protein and 0.61 +/- 0.07 pmol/mg protein, respectively). The apparent Kd values for high affinity sites (0.15 nM) and for low affinity sites (4 nM) were not altered either by the gestational age of the cells or by PTH treatment. With respect to the EGF-dependent phosphorylation in membranes of trophoblast cells in culture, it was found that the phosphorylation of two major proteins of 175 kilodaltons and 35 kilodaltons, is greatly increased in PTH-treated cell membranes in the presence of EGF. This PTH-induced effect on EGF receptors was associated with an augmented functional response of trophoblastic cells to EGF. PTH increased the EGF-stimulated secretion of hCG. These results demonstrate that PTH increases the number of biologically active EGF receptors during the in vitro differentiation of human trophoblast cells. This PTH-induced effect suggests a role for this hormone in the regulation of the growth and the endocrine functions of these cells.     

Subcutaneous degradation of biosynthetic human growth hormone in growth hormone deficient patients

The aim of the present study was to look further into the question of local degradation of sc injected human GH in GH deficient patients. A comparison was made of serum GH levels after constant iv and sc infusion of the same amount of GH (33 ng.kg-1.min-1) in the same 9 GH deficient patients. A 3-h lag period was interposed between the iv and the sc infusion. Iv infusion was continued for 3 h. All 9 subjects subsequently received sc infusion for 19 h and five of them continued for additionally 24 h. The mean steady state serum GH level in the nine patients was 23.1 +/- 5.1 micrograms/l after iv and 6.8 +/- micrograms/l after sc administration (P less than 0.01). Extension of the sc infusion period in 4 of the subjects did not significantly alter the serum GH level (P less than 0.15), implying that a steady state was reached. The GH in the infusion system was stable throughout a 24-h period. We therefore conclude that sc injected GH is degraded locally to a substantial extent.     

Dose dependence of growth response to human growth hormone in growth hormone deficiency.

A trial of the relative effect on growth of 20 IU/week and 10 IU/week of human growth hormone has been made in 38 patients with "isolated" growth hormone deficiency over 1 year of treatment, 18 patients over 2 years and 10 over 3 years, and in 17 patients with surgically treated craniopharyngiomata over 1 year. The velocity of height growth in the first year of treatment, compared with a full year of pre-treatment control, was 1.3 times as great in both groups of patients on the larger dose as it was in those on the smaller one. Second-degree equations fitted to the treatment catch-up curve gave estimates of 1.7 cm more height gained on the larger dose by the end of the first year, 2.7 cm by the end of the second, and 3.4 cm by the end of the third. Adjusting treatment increment by covariance for bone age at the beginning of treatment, pre-treatment velocity, and body surface area did not alter these mean differences. Bone age velocity during treatment was the same in both treatment groups (mean 1.09 "years"/year in the first year); thus we anticipate a gain in final adult height of the order of 10 cm from employing the larger dose. The decrease in skin folds occurring on treatment, however, was no different with the larger than with the smaller dose. This reinforces previous observations that the short-term metabolic and longer-term auxologic effects of hGH are not necessarily related.     

The secretory patterns of growth hormone in pregnant and hysterectomized ewes.

This work was undertaken to determine the secretory patterns of GH during pregnancy, and to evaluate the effect, if any, of hysterectomy during early pregnancy on subsequent secretion of GH in ewes. The concentrations of GH were determined in the plasma of jugular blood samples collected at 15-min intervals during a 6-h period on days 20, 40, 60, 80, 100 and 120 post-mating, and three times per week between days 29 and 120 post-mating from 5 pregnant ewes and from 5 ewes from which the gravid uterus was removed on day 30 post-mating. A pulse analysis program (Pulsar) was used to analyse the secretory patterns of GH in individual profiles of the serial sampling period. In the two groups of ewes, peripheral concentrations of GH fluctuated in an episodic manner during the frequent blood sampling of any stage of the post-mating period examined. The overall GH concentrations, the basal GH concentrations, the frequency and the amplitude of GH pulses remained fairly stable between days 20 and 120 post-mating in the two groups of ewes. The parameters of GH secretion were not different between the two groups of ewes. The secretory patterns of GH, as determined in plasma of blood collected three times per week between days 29 and 120 post-mating were also not different between the two groups of ewes. In conclusion, results of this study show that (i) the pulsatile secretion of GH does not change as pregnancy advances, and (ii) hysterectomy performed during early pregnancy does not subsequently affect the secretory patterns of GH. These findings suggest that the gravid uterus and/or the feto-placental unit secretory products are unlikely to be involved in the control of GH secretion during pregnancy in the ewe.