Paul Beck

The renin-aldosterone system in mother and fetus at term

Umbilical cord plasma aldosterone consistently exceeded that of paired maternal plasma (N=24), although plasma renin activity (N=15) and reinin substrate (N=25) were always higher in the mother. This dissociation of levels of aldosterone and its stimulating hormone renin may be due to (1) a different stimulus for aldosterone secretion in the fetus, (2) increased fetal sensitivity to renin-produced angiotensin II, or (3) altered fetal metabolism of the latter hormone.

Correlation of gestational age with maternal human chorionic somatomammotropin and maternal and fetal growth hormone plasma concentrations during labor

Abstract The effect of gestational age on the interrelationships between infant weight (n = 464) and maternal (n = 331) and cord (n = 464) growth hormone (GH) concentrations and maternal (n = 326) human chorionic somatomammotropin (HCS) levels was determined in unselected obstetric patients delivered of infants between 31 and 45 weeks of gestation. A significant negative correlation (r = −0.113) was observed between gestational age and maternal HCS. After correction for gestational age, there was a low but significant correlation between infant weight and maternal HCS (average r = 0.129) and between HCS and placental weight (average r = 0.308). The mean HCS levels of patients admitted in the late stages of labor was significantly lower than those admitted in the earlier stages. Surprisingly, a significant negative correlation (r = −0.203) was observed between cord GH level and infant weight. The low order of correlation between HCS and infant weight indicates that single HCS determinations drawn during labor are a poor indicator of fetal size.

Hypothalamic Sarcoidosis and Hypopituitarism

4 patients with presumed pituitary hypothalamic sarcoidosis are described. 3 had histological diagnoses compatible with sarcoidosis and in the other this diagnosis was strongly suspected from chest X-rays. 2 patients presented with diabetes insipidus. ACTH reserve was diminished in 3 out of 4 and growth hormone reserve was diminished in the 3 who were tested. All 4 patients developed secondary amenorrhea. 3 patients had hypothalamic hypothyroidism. Prolactin dynamics were intact. Tomograms of the sella turcica in all 4 and computerized tomography of the hypothalamic area in 2 patients failed to reveal any abnormality.

Estriol Modification of the Effects of Progesterone and Human Chorionic Somatomammotropin on Glucose Tolerance and Plasma Insulin in Rhesus Monkeys

The effects of estriol and estradiol on progesterone-induced changes in glucose and insulin metabolism have been studied in mature female rhesus monkeys. The addition of striol to treatment regimens containing progesterone only or human chorionic somatomammotropin (HCS) plus progesterone resulted in improvement in mean glucose disappearance rates following intravenous glucose administration without significant changes in the mean total insulin responses to glucose. This change in glucose tolerance was primarily due to apparent improvement in peripheral glucose utilization rather than any increment in total or initial insulin responses to glucose. By contrast, the addition of estradiol to the progesterone treatment regimen produced no changes in the mean glucose disappearance rate or the plasma insulin response to glucose, although there was an increase in mean fasting glucose and insulin concentrations after estradiol + progesterone treatment. These results indicate that estriol and estradiol have different effects on glucose and insulin metabolism and suggest that estriol may modify the diabetogenic tendencies of progesterone and HCS during primate pregnancies.

Effects of Gonadal Hormones and Contraceptive Steroids on Glucose and Insulin Metabolism

Considerable data have been accumulated regarding the effect of naturally-occurring and synthetic sex steroids on glucose and insulin metabolism. The studies have been performed largely to elucidate the mechanisms responsible for changes in carbohydrate metabolism during pregnancy. Initially, studying glucose tolerance in women treated with contraceptive steroids seemed to be a logical way to dissociate the effects of gonadal steroids from the metabolic effects of human placental lactogen during gestation. However, such studies have been confusing and often apparently contradictory. Yet, if the structural characteristics of the steroid compounds tested are considered, these results are basically in agreement with, rather than contradictory to, data obtained earlier in laboratory animals. If one correlates the changes in glucose or insulin metabolism with the chemical structure of the estrogen or progestin tested, it is possible to show that there are clear structure-activity relationships between the compounds tested and the results observed, which appear to be modified by the functional state of the pancreatic islet cells in the subjects tested.

Insulin response to fructose and glucose infusions into the sheep fetus.

Summary Twenty g/100 ml of glucose or fructose solutions at a dose of 2 g/kg were injected into the fetal circulation of pregnant sheep over a gestational age range from 110 days to term. Fourteen fructose injections and 8 glucose injections were carried out in a total of eight fetuses. Fetal plasma insulin concentrations increased significantly after either fructose or glucose injections. After glucose injection, the rise in fetal plasma insulin concentration was most marked and fructose concentrations in the fetal circulation increased.

The role of human chorionic somatomammotropin (HCS) and gonadal steroids in gestational diabetes

RiassuntoDurante la gestazione, la tolleranza ai carboidrati nella madre sembra alterata da almeno due meccanismi: 1) diminuita sensibilità dei tessuti insulino-sensibili allazione ipoglicemizzante dellinsulina, e 2) alterata sensibilità delle isole di Langerhans allo stimolo insulinogenico del glucosio. Leffetto di quantità fisiologiche di estriolo e di estradiolo non coniugati su questi parametri è tuttora sconosciuto. Una riduzione della sensibilità allinsulina può essere indotta sperimentalmente, in scimmie Rhesus femmine, con la somministrazione di somatomammotropina corionica umana (HCS) e di progesterone. La somministrazione di progesterone determina un aumento dellinsulina prodotta sotto lo stimolo del glucosio, sia nelle scimmie che nelluomo. Al contrario, la somministrazione di HCS neutralizza laumento della risposta insulinemica al glucosio, provocato nelle scimmie dal progesterone, e ritarda effettivamente la produzione di insulina in risposta al glucosio in donne con diabete subclinico. Questultimo tipo di risposta è simile, ma non identico, a quello che si osserva in donne con diabete della gravidanza. Resta da stabilire se il progesterone e/o gli estrogeni elaborati dal prodotto del concepimento alterino leffetto dellHCS sulla produzione di insulina o sulla sensibilità allinsulina in donne normali o con diabete subclinico.RésuméAu cours de la grossesse, la tolérance aux glucides de la mère résulte altérée par au moins deux mécanismes: 1) sensibilité réduite des tissus insulino-sensibles à laction hypoglycémiante de linsuline, et 2) sensibilité altérée des îlots de Langerhans à la stimulation insulinogénique par le glucose. Leffet de quantités physiologiques destriol et destradiol non conjugués sur ces paramètres est encore inconnu. Une réduction de la sensibilité à linsuline peut être obtenue expérimentalement, chez les guenons Rhesus, par ladministration de somatomammotropine chorionique humaine (HCS) et de progestérone. Ladministration de progestérone provoque une augmentation de la sécrétion insulinique stimulée par le glucose, aussi bien chez les guenons que chez lhomme. Au contraire, ladministration de HCS neutralise laugmentation de la réponse insulinémique au glucose provoquée chez les guenons par la progestérone et retarde effectivement la production dinsuline en réponse au glucose chez les femmes avec diabète infraclinique. Le dernier type de réponse est semblable mais non identique à celui que lon peut observer chez les femmes avec diabète de la grossesse. Il reste à établir si la progestérone et/ou les estrogènes élaborés par le produit de la conception altèrent leffet de lHCS sur la production insulinique ou sur la sensibilité à linsuline chez les femmes normales ou avec diabète infraclinique.ResumenDurante la gestación, la tolerancia para los carbohidratos en la madre parece alterada al menos por dos mecanismos: 1) por la menor sensibilidad de los tejidos insulinosensibles a la acción hipoglicémica de la insulina, y 2) por la alterada sensibilidad de las islas de Langerhans al estímulo insulinogénico de la glucosa. El efecto de cantidades fisiológicas de estriol no asociado y de estradiol en estos parámetros todavía se desconoce. Experimentalmente se puede inducir en monos Rhesus hembras una reducción de la sensibilidad a la insulina con el suministro de somatomammotropina coriónica humana (HCS) y de progesterona. El suministro de progesterona determina un aumento de la insulina producida bajo el estímulo de la glucosa, tanto en los monos como en el hombre. Por el contrario, el suministro de HCS neutraliza el aumento de la reacción insulinémica, provocada en los monos por la progesterona, y retrasa efectivamente la producción de insulina como reacción a la glucosa en las mujeres con diabetes subclínica. Este último tipo de reacción es semejante, pero no idéntico, al que se observa en mujeres con diabetes de gestación. Queda por establecer si la progesterona y/o los estrógenos elaborados por el producto de la concepción alteran el efecto del HCS en la producción de insulina o en la sensibilidad a la insulina en mujeres normales o con diabetes subclínica.ZusammenfassungWaehrend der Schwangerschaft erscheint die Kohlenstoff-Toleranz der Mutter zumindest durch zwei Mechanismen gestoert: 1) Verminderte Sensibilitaet der insulin-empfindlichen Gewebe gegenueber der blutzuckersenkenden Wirkung des Insulins und 2) Veraenderte Sensibilitaet der Langerhansschen Inseln gegenueber dem insulinogenen Reiz der Glukose. Die Wirkung von physiologischen Mengen nicht konjugierten Oestriols und Oestradiols auf diese Parameter ist noch unbekannt. Eine Herabsetzung der Insulinempfindlichkeit kann bei weiblichen Rhesus-Affen durch die Verabreichung von chorionischem Human-Somatomammotropin (HCS) und Progesteron experimentell induziert werden. Die Verabreichung von Progesteron bewirkt sowohl beim Affen wie auch beim Menschen eine Zunahme des unter dem Reiz der Glukose produzierten Insulins. Im Gegensatz dazu neutralisiert die Verabreichung von HCS die Zunahme der insulinaemischen Antwort auf Glukose, welche bei Affen durch Progesteron hervorgerufen wird und verzoegert tatsaechlich die Insulinproduktion nach Glukose bei Frauen mit subklinischem Diabetes. Der letzte Antwort-Type aehnelt ist aber nicht derselbe wie derjenige der bei Frauen mit Schwangerschaftsdiabetes beobachtet wird. Es muss noch festgestellt werden ob das Progesteron und/oder die durch die Frucht ausgearbeiteten Oestrogene den Effekt von HCS auf die Insulinproduktion oder die Insulinsensibilitaet bei normalen Frauen oder Frauen mit subklinischem Diabetes veraendern.SummaryMaternal carbohydrate tolerance during gestation appears to be altered by at least two mechanisms: 1) decreased sensitivity of insulin-sensitive tissues to the hypoglycemic action of insulin, and 2) alterations in the sensitivity of the islets of Langerhans to the insulinogenic stimulus of glucose. The effect of physiologic amounts of unconjugated estriol and estradiol on these parameters is as yet unknown. Decreased sensitivity to insulin can be produced experimentally in female Rhesus monkeys by human chorionic somatomammotropin (HCS) and by progesterone administration. Progesterone administration enhances glucose-stimulated insulin production in both monkeys and man. By contrast, HCS administration reverses the progesterone-enhanced serum insulin response to glucose in monkeys and actually retards insulin production in response to glucose in subclinical diabetic women. The latter pattern of insulin response is similar to, but not identical with, that seen in women with gestational diabetes. Whether progesterone and/or the estrogens elaborated by the conceptus alter the effect of HCS on insulin production or sensitivity to insulin in normal or subclinical diabetic women remains to be determined.