Search

Adrenocortical insufficiency was produced in rat fetuses by surgical decapitation. These animals show low plasma corticosterone levels compared to littermate controls. Lung slices from anencephalic fetuses were found to have reduced incorporation of [14C]choline into phosphatidylcholine, hence diminished choline pathway activity; this abnormality was present at 21 days of gestation but not at term. Cholinephosphotransferase (CPT), the terminal catalyst of the choline pathway, also showed diminished activity in lungs of anencephalic fetuses, with a mean of 120 pmol/min/mg protein compared to a control value of 190. Dexamethasone treatment of these animals for 6–12 hr led to enhanced choline incorporation rates. Corticosteroid administration also restored CPT activity and even elevated the enzyme to a mean level (340 pmol/min/mg protein) greater than that found in normal fetuses at 21–22 days of gestation. The early pulmonary biochemical effects of dexamethasone in this model were not accompanied by recognizable ultrastructural changes.

The testes of mice with testicular feminization (tfm/y) are small (10% of normal), cryptorchid, and composed of immature tubular elements surrounded by several layers of peritubular cells and enlarged Leydig cells. Morphometric analyses indicated a normal or slightly reduced number of Leydig cells per tfm/y testis. Electron microscopy revealed that these cells have smooth surfaces devoid of microvilli and contain increased quantities of lipid and mitochondria but relatively little endoplasmic reticulum (SER). Mitochondria occupied the major volume of the cytoplasm. These regularly round organelles with tubular cristae rarely contained dense bodies or lipid globules. SER in tubulovesicular, lamellar, or whorl-like complexes were never observed.Testes from tfm/y animals contained elevated levels of several Leydig cell oxidative enzymes. 17-β-Hydroxysteroid dehydrogenase activity was normal at birth but significantly reduced in the adult. As a result, testosterone synthesis was reduced 6 to 21 times in testes from tfm/y mice.Collectively these studies suggest that tfm/y Leydig cells are arrested in cytodifferentiation at a stage comparable to the normal animal at birth even though there is adequate gonadotrophin stimulation. Since tissues of the tfm/y mice are insensitive to testosterone it appears that androgen actionon the Leydig cell may be necessary for its maturation.

Decapitation in uteroproduces hormonal deficiencies which do not influence lung organogenesis but retards pneumocyte differentiation at the organelle and molecular levels. Such lungs contain decreased quantities of phospholipid and functionally are impaired in their ability to reduce surface tension to normal levels. The mechanisms by which these alterations are produced are most likely related to hormonal deficiencies during fetal development. These deficiencies may specifically alter lung phospholipid metabolism. Retardation of phospholipid metabolism may, however, be secondary to a more generalized retardation of pneumocyte differentiation. We favor the latter hypothesis in so far as pituitary failure occurring in man and animals with fully mature lungs does not lead to clinical respiratory distress (33, 38). Further inquiry into the manner in which hormones influence lung metabolism will require evaluation of the effect of specific hormonal replacements on in uterodecapitated or hypophysectomized fetuses and on lung explants differentiating in vitro.

The administration of a relatively high dose of delta-1 hydrocortisone to pregnant rats results in severe morphologic changes in virtually all of the placental tissues. As early as the fifteenth day of pregnancy, there is a marked inhibition of decidua formation and a severe decrease in decidual and “junctional zone” glycogen. In addition, delta-1 hydrocortisone inhibits trophoblastic proliferation and induces morphologic changes in the syncytial trophoblast which resemble “premature aging.” The over-all effect of these changes leads to a failure in placental growth during the eighteenth day of gestation and thereafter. The yolk sac epithelium becomes depleted of glycogen as early as the fifteenth day whereas the apical P.A.S.-positive granulations continue to increase in number until term, a process which leads to marked “clubbing” of the individual epithelial cells. These processes undoubtedly alter placental function severely and are reflected by a significant increase in intrauterine fetal death.