Joseph B Warshaw

Bio: Joseph B Warshaw is an academic researcher from Albert Einstein College of Medicine. The author has contributed to research in topics: Glycogen & Corticosterone. The author has an hindex of 3, co-authored 3 publications receiving 57 citations. Previous affiliations of Joseph B Warshaw include University of Texas System.

Placental growth and glycogen metabolism in streptozotocin diabetic rats

Abstract: Summary The present study was designed to construct a develo~mental Placental glycogen metabolism was investigated in rat pregnancies comolicated bv stre~tozotocin-induced diabetes mellitus. Both ". diabetic and control placentas had increasing glycogen concentration from day 14 to day 16, after which glycogen concentration declined rapidly. The diabetic placentas had significantly elevated glycogen concentration when compared to controls from day 16 through term (day 22). Near term, when control glycogen content fell close to zero, the diabetic placentas still had appreciable glycogen levels. Total phosphorylase activity in the diabetic placentas was significantly higher than control values from day 16-22. Phosphorylase A activity, however, was lower in the diabetic placentas late in gestation, corresponding to the increased glycogen concentration seen at that time. Diabetic placentas had increased total synthase activity on the final 3 days of gestation, although synthase A activity was lower than corresponding control values. The placentas in this model are markedly increased in size late in gestation. No difference in protein concentration or protein/ DNA ratio was noted. Total DNA content per placenta was significantly increased in the diabetic placentas after day 16 when compared to controls. Placental DNA in the diabetics continued to increase until day 18-19 of gestation, whereas DNA content in control placentas remained constant after day 16. Thus, the diabetic placentas apparently continue the process of DNA replication after DNA synthesis is complete in the controls.

Fetal and maternal corticosterone and corticosteroid binding globulin in the diabetic rat gestation.

Abstract: Delayed fetal lung development is a feature of the diabetic pregnancy. Since fetal glucocorticoids are important in the regulation of lung maturation, we measured corticosterone and corticosteroid-binding globulin binding capacity in streptozotocin-diabetic pregnant rats and their fetuses. Previous studies have demonstrated delayed fetal lung maturation in this animal model. In control fetuses, total corticosterone concentration increased through day 20 of gestation, then declined until day 22 (term). The unbound steroid, which accounted for 5-10% of the total, increased approximately 3-fold from day 18 to term. Corticosteroid-binding globulin binding capacity peaked on day 19 after which it decreased. Maternal total and unbound corticosterone levels and corticosteroid-binding globulin binding capacity remained relatively constant throughout the final week of normal gestation. When compared to controls, fetuses from diabetic pregnancies had significantly lower total corticosterone from day 19 through 22. Corticosteroid-binding globulin binding capacity was also significantly decreased in these fetuses for the last 4 days of gestation. Similar differences were noted in maternal samples. However, no significant differences in unbound, biologically active, corticosterone were seen when diabetic and control groups were compared. Thus, delayed fetal lung maturation observed in fetuses of streptozotocin-diabetic rats is associated with a decrease in total circulating corticosteroid levels late in gestation. However, since unbound corticosteroid levels were similar in fetuses of control and diabetic animals, it is likely that other mechanisms may be responsible for the observed delay in lung development in fetuses of diabetic pregnancies.

263 histologic abnormalities in the diabetic rat placenta

Abstract: In previous work with the diabetic (DM) pregnant rat we found placentas to be larger and fetuses smaller than normal. To study cellular differences that might contribute to the disparity in size and function of DM placentas, we analyzed by light and electron microscopy DM and control placentas on days 14, 18, and 22 (term). DM was induced using IV streptozotocin (45 mg/kg). DM placentas (days 18 and 22) were marked by the presence of large numbers of glycogen-distended cells in the junctional zone. The trophoblastic layers in the interhemal membrane were also significantly thicker in the DM group, and large accumulations of lipid droplets were prominent. Since there is normally a striking thinning of the labyrinthine placental barrier by day 22, the thickness of age-matched DM placentas is more impressive, and possibly increases the diffusion distance in the DM placentas. Moreover, 22-day DM placentas contained more glycogen and rough endoplasmic reticulum in the inner trophoblastic layer, a feature similar to 18-day control placentas. Thus, DM placentas have a number of features that are normally seen earlier in gestation. Histologic evidence confirms increased glycogen and lipid in both the junctional zone and in the cellular barrier between maternal and fetal blood. We speculate that the thickening and modifications of the cellular barrier in DM may affect fetal growth and nutrition by increasing the diffusion distance between the maternal and fetal circulations.

Spring Declines in Microtus pennsylvanicus and the Role of Steroid Hormones

Abstract: Spring declines are a common feature of small mammal demography. We tested the hypothesis that meadow voles from populations experiencing severe spring declines should exhibit severe stress responses as indicated by high free corticosterone levels. Three populations in southern Ontario were live-trapped intensively in the spring of 1985, all animals were bled each time, and measurements of total corticosterone, corticosterone-binding globulin (CBG), and total androgen (testosterone and dihydrotestosterone) were obtained by radioimmunoassay

Circadian rise in maternal glucocorticoid prevents pulmonary dysplasia in fetal mice with adrenal insufficiency.

Abstract: The hypothalamic-pituitary-adrenal (HPA) axis, including hypothalamic corticotropin-releasing hormone (CRH) and pituitary corticotropin, is one of the first endocrine systems to develop during fetal life, probably because glucocorticoid secretion is necessary for the maturation of many essential fetal organs. Consistent with this, pregnant mice with an inactivating mutation in the Crh gene deliver CRH-deficient offspring that die at birth with dysplastic lungs, which can be prevented by prenatal maternal glucocorticoid treatment. But children lacking the ability to synthesize cortisol (because of various genetic defects in adrenal gland development or steroidogenesis) are not born with respiratory insufficiency or abnormal lung development, suggesting that the transfer of maternal glucocorticoid across the placenta might promote fetal organ maturation in the absence of fetal glucocorticoid production. We used pregnant mice with a normal HPA axis carrying fetuses with CRH deficiency to characterize the relative contributions of the fetal and maternal adrenal to the activity of the fetal HPA axis, and related these findings to fetal lung development. We found that in the presence of fetal adrenal insufficiency, normal fetal lung development is maintained by the transfer of maternal glucocorticoid to the fetus, specifically during the circadian peak in maternal glucocorticoid secretion.

Ontogeny of corticosteroid-binding globulin biosynthesis in the rat.

Abstract: In plasma, glucocorticoids are transported by corticosteroid-binding globulin (CBG), which is synthesized primarily in the liver. Plasma levels of maternal and fetal CBG fluctuate during gestation, and this may be due to changes in the biosynthesis and/or clearance of the protein. We have, therefore, studied the ontogeny of CBG biosynthesis in the rat by using a solution hybridization assay to measure hepatic CBG mRNA levels. The results indicate that the concentration of CBG mRNA is exceptionally high in 15-day-old fetal livers (55.1 pg CBG mRNA/μg total RNA), but declines to very low levels at birth (day 21). During the same period, CBG mRNA levels in maternal livers remained relatively constant (18.9–23.1 pg CBG mRNA/μg total RNA). Hepatic CBG mRNA levels were barely detectable 1 week after birth, and a sex difference was apparent by 2 weeks of age, with higher levels in female livers. Although adult CBG mRNA levels were attained by 3 weeks of age, serum CBG concentrations did not reach adult values fo...