Advances in physiology of human lactation.
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Biomedical subjects
Publications and source records attributed to C Robyn.
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Among 28 menstruating women tested once randomly during the cycle, somatomedin-C (Sm-C) values were lower in the 10 women in normal follicular phase than in the 10 women in normal luteal phase or the 8 women with hyperandrogenism. Among these 28 subjects, Sm-C showed a positive correlation with testosterone and a positive correlation of borderline significance with oestradiol. A positive correlation was also evidenced between Sm-C and in progesterone among the 20 women of this group who were not hyperandrogenic. In 5 other normal women investigated daily throughout an entire menstrual cycle, Sm-C concentrations were higher during days +4 to +9 of this cycle (luteal phase) than during days -3 to -8 (follicular phase). In another group of 21 healthy women, Sm-C values were increased during medroxyprogesterone acetate (150 mg trimestrially) treatment. In 7 normal men, Sm-C decreased during ethinyl-oestradiol (1 mg daily for 5 days) administration. These findings suggest that circulating Sm-C levels are modulated by variations of sex steroids which occur during the menstrual cycle as well as by pharmacological doses of oestrogens and progestagens.
The mechanisms whereby growth hormone (GH) secretion is decreased in human obesity remain obscure. We studied the response of plasma GH and prolactin (PRL) to an I.V. dose of 0.5 mcg/kg of growth hormone releasing factor (GRF) in three groups of children: lean (N = 12), obese (N = 15) and GRF-deficient, i.e. children with complete GH deficiency on the basis of conventional provocative testing and evidence of hypothalamic dysfunction on the basis of thyrotropin-releasing hormone testing (N = 7). Mean (+/- SEM) peak plasma GH after GRF was blunted to the same extent in obese and in GRF deficient children (11.1 +/- 2.2 and 8.3 +/- 2.8 ng/ml) as compared to lean control children (34.7 +/- 4.7 ng/ml). The pattern of PRL response to GRF was however different in GRF deficient children, whose high basal PRL levels increased further after GRF injection, and in obese and lean children, who had n alpha acute change in PRL levels after GRF. Baseline plasma somatomedin C concentrations were low for age in GRF deficient children and tended to be high for age in obese children. On the basis of these discrepant patterns of response of PRL to GRF and plasma somatomedin C concentrations, we conclude that GRF deficiency does not account for the decreased GH secretion observed in obese children.
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A new type of inexpensive horizontal apparatus for the electrophoretic transfer of proteins from a gel to an immobilization membrane has been developed. In this system, gel and membrane were directly pressed between two flat electrodes. A surface-conductive glass was used as anode and a stainless-steel plate as cathode. Proteins could be transferred from polyacrylamide gel to nitrocellulose sheet, with a yield of at least 90% in 60-90 min, without overheating, using a voltage gradient of 30-40 V/cm. Moderate volumes of separate anodic (with 20% methanol) and cathodic (with 0.1% sodium dodecyl sulfate) buffers were suited for optimal transfer of proteins with relative molecular mass (Mr) in the 14,000-94,000 range.
A total of 1036 nursing mothers were investigated for their nursing behaviour, status of nutrition and menstrual cycle, serum prolactin and progesterone; 61 in Sweden, 457 in an urban area of Zaïre (Bukavu, Kivu) and 518 in a rural area of the same region (Kabare, Kivu). Lactational hyperprolactinaemia is influenced by the frequency but not by the duration of suckling. The return of luteinization of follicles, but not that of menstrual bleeding, was inversely related to the degree of lactational hyperprolactinaemia. Significant luteinization took place in only some 10% of the mothers during the first three months of lactation in Sweden and within the first year in Zaïre. In these mothers with luteinized follicles the average progesterone was only slightly above 1.0 ng/ml indicating poor luteinization. Lactational hyperprolactinaemia, the return of menstruation and luteinization during lactation were not related to the nutritional status as evaluated by the body weight indices and serum albumin. However, suckling and hyperprolactinaemia do not appear to be the only factors involved in the control of fertility during lactation. When serum prolactin levels were equally low, i.e. below 500 microU/ml, twice the number of lactating mothers with signs of luteinization were found in the urban than in the rural population of Zaïre.
We studied the effect of a single intravenous bolus of 0.5 microgram/kg of growth hormone-releasing factor (GRF) on plasma GH, prolactin (PRL) and somatomedin C (SMC) in 12 short normal children and 24 patients with severe GH deficiency (GHD), i.e. GH less than 5 ng/ml after insulin and glucagon tolerance tests. GRF elicited an increase in plasma GH in both short normal and GHD children. The mean GH peak was lower in the GHD than in the short normal children (8.2 +/- 2.5 vs. 39.2 +/- 5.1 ng/ml, p less than 0.001). In the GHD patients (but not in the short normals) there was a negative correlation between bone age and peak GH after GRF (r = -0.58, p less than 0.005); GH peaks within the normal range were seen in 5 out of 8 GHD children with a bone age less than 5 years. In the short normal children, GRF had no effect on plasma PRL, which decreased continuously between 8.30 and 11 a.m. (from 206 +/- 22 to 86 +/- 10 microU/ml, p less than 0.005), a reflection of its circadian rhythm. In the majority of the GHD patients, PRL levels were higher than in the short normal children but had the same circadian rhythm, except that a slight increase in PRL was observed 15 min after GRF; this increase in PRL was seen both in children with isolated GHD and in those with multiple hormone deficiencies; it did occur in some GHD patients who had no GH response to GRF. Serum SMC did not change 24 h after GRF in the short normal children. We conclude that: (1) in short normal children: (a) the mean GH response to a single intravenous bolus of 0.5 microgram/kg of GRF is similar to that reported in young adults and (b) GRF has no effect on PRL secretion; (2) in GHD patients: (a) normal GH responses to GRF are seen in patients with a bone age less than 5 years and establish the integrity of the somatotrophs in those cases; (b) the GH responsiveness to GRF decreases with age, which probably reflects the duration of endogenous GRF deficiency, and (c) although the PRL response to GRF is heterogeneous, it does in some patients provide additional evidence of responsive pituitary tissue.
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Five highly purified preparations of human pituitary prolactin, widely used in radioimmunoassays, were analyzed by immunoperoxidase electrophoresis with rabbit antisera raised against ovine and rat prolactin. When unreduced, the prolactin content of these preparations was separated into one major prolactin-like immunoreactive band of Mr 23,000, and four fainter immunoreactive bands of Mr's 16,000, 22,000, 25,000, and 45,000. Increasing the 2-mercaptoethanol concentration modified the relative proportions and the Mr of immunoreactive bands so that, after extensive reduction, only two immunoreactive bands were separated, one major band of Mr 25,000 and one fainter band of Mr 17,000. A direct relationship existed between the load of prolactin submitted to electrophoresis in the 0.25 to 75 ng range and the optical density of the separated bands.
Circulating levels of glucose and particularly those of insulin are significantly lower in African mothers (Kivu, Zaire) nursing their infants than in non pregnant and non lactating women of the same area. Furthermore, the glycemia and the insulinemia increase relatively less after a glucose load in the breastfeeding mothers. The lack of glucose available to the mammary gland may explain the low volumes of milk produced by the lactating mothers in this region of Africa.
A group of women with unknown last menstrual period was studied representing 16% of a total of 22 404 pregnant women recorded using a common perinatal form. Unknown menstrual period is associated with high rates of low birth weight and with low socioeconomic and sociodemographic status. Such characteristics are also associated with a high rate of preterm deliveries. Thus any possible bias introduced in studies of prematurity by ignoring the group of women with unknown last menstrual period should be carefully checked.
This paper starts with a short description of the history of the discovery of the hydatidiform mole ( Tulp in 1641) and of the treatment (before 1956, hysterectomy in most cases). After 1961 chemotherapy started to be used even in patients who had cerebral metastases. 72 patients who had attended Professor Hubinont 's department in the University Hospital of Saint-Pierre in Brussels between January 1971 and December 1981 were followed up. Questionnaires were sent to the patients and to their doctors who were treating them in order to try and find out what had happened in subsequent pregnancies and what the maternal and fetal consequences and complications were. The social class and the marital status of the patients was also considered as well as their wish to become pregnant again. Of the 72 cases that were followed up after evacuation 63 (87.5%) recovered while 9(12.5%) had clinical, biological or radiological signs of persistent non-metastatic (3) and metastatic (6 cases) active disease. The department asked patients not to become pregnant in the year following evacuation of the mole. 10% were sterilised, 4 by hysterectomy and 4 by tubal ligation. 42% used the oral contraceptive pill and 34% (24 cases) condoms. Control follow-up of patients who became pregnant was compared with a group of 2 529 pregnancies in Saint-Pierre Hospital during the year 1981. 44 out of the 72 patients who were followed up after hydatidiform mole became pregnant with a total of 52 pregnancies. Ten became pregnant in the first 6 months after attempting it, 11 between 6 and 12 months and 23 after a delay of 12 months. Out of the 52 pregnancies, 34 5%) had a live baby at term. 6 were premature and 31 out of 34 babies delivered at term were delivered vaginally and 3 by Caesarean. There were 9 spontaneous abortions (17%) and 2 terminations of pregnancy (4%). Three patients had repeated non-intentional abortions and one had a still-birth for which the cause could not be found. Only one other had a second mole. When these results are compared with the histories of these patients before they had the hydatidiform mole there did not seem to be any increase in the number of spontaneous abortions or premature labours, nor was there when this group was compared with a control group. Only one of the 38 live-born children showed a major congenital abnormality which was varus equinus. There was no possibility of picking out statistically anything of value as far as congenital malformations was concerned.
Immunoperoxidase electrophoresis, combining SDS--ME--PAGE and the 'double bridge' immunoperoxidase staining was applied to crude human pituitary homogenates. With anti-hGH and anti-hPL sera, 4 hGH-related monomers were characterized: a Mr 22 000 peptide corresponding to hGH; a Mr 20 000 peptide corresponding to the known hGH variant and two unknown hGH variants (Mr 65 000 and Mr 75 000). With anti-ovine, rat and human PRL sera, 4 PRL-related monomers were immunostained: one comigrated with purified hPRL (Mr 25 000), and 3 were unknown (Mr 29 000; Mr 45 000; Mr 16 000).
Animal experiments and clinical data indicate that prolactin (PRL) induces hyperinsulinemia and even diabetes. The effects of PRL on carbohydrate metabolism may be explained by at least two different mechanisms. Either PRL induces an insulin resistance at the peripheral tissue level, or PRL has a direct cytotropic effect on the pancreatic islets. Obviously, both mechanisms inducing hyperinsulinemia may coexist. We report here immunocytochemical evidence that PRL is localized in the endocrine pancreas of the normal adult rat. More precisely, the immunoreactive PRL is distributed in the cytoplasm of insulin-secreting B cells. These findings support a direct action of PRL on the endocrine pancreas.
Intravenous injections of 50 micrograms corticotropin-releasing factor (CRF) to four normal men at 0900 and 2300 h were followed by significant plasma ACTH and cortisol elevations, without changes in GH and PRL concentrations. The responses were more easily assessed late in the evening than in the morning, when they were superimposed upon the spontaneous hormonal variations. The initial hormonal response was always followed by a period of decreased hormonal values compared to control patterns. The normal pituitary-adrenal response to CRF was blunted or abolished by prior administration of dexamethasone. These data suggest that exogenous administration or CRF-induced endogenous production of glucocorticoids modulates the sensitivity of corticotropic cells to the action of CRF. Since normal ACTH and cortisol secretory episodes are likely to obscure the effects of CRF, stimulation tests for clinical purposes should be performed during the quiescent period, i.e. late in the evening.
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Gestational trophoblastic tumours group together the complete hydatidiform mole (classical) and partial mole (with fetus), invasive mole and choriocarcinoma. Genetically, trophoblastic tumours can arise in different ways: they can derive from normal zygotes with the maternal and paternal haplotype (normal pregnancy), or from a triploid zygote (partial mole) or from an XX zygote possessing only a duplicated male haplotype and no maternal contribution (complete mole). The low malignancy rate in partial mole (2.4%) compared to the complete mole (10 to 20%) remains unknown. Further analysis of the genetics of these tumours may well contribute to the understanding of the process of carcinogenesis.